Sherry Boschert

SAN FRANCISCO – To save a patient in septic shock, think SAVE.

The acronym stands for Suspicion, Act, Ventilation/oxygenation, and Evaluate the goals, Dr. Robert J. Vissers said at the annual meeting of the American College of Emergency Physicians.

He adapted the SAVE acronym from the 2011 Critical Points continuing medical education course for emergency physicians.

Suspicion starts with recognizing systemic inflammatory response syndrome (SIRS), which combined with an infection constitutes sepsis. Patients have SIRS if they have at least two of the following: temperature higher than 38° C or below 36° C; heart rate faster than 90 beats per minute; white blood cell count over 12,000 or less than 4,000 cells/mcL or with greater than 10% bands (immature forms); and a respiratory rate over 20 breaths per minute or, on blood gas, a partial pressure of carbon dioxide less than 32 mm Hg.

Patients with sepsis and organ dysfunction, hypoperfusion, or hypotension have severe sepsis and are considered to have septic shock if the hypotension or hypoperfusion is refractory to fluid resuscitation, said Dr. Vissers, chief of emergency medicine at Legacy Emanuel Hospital, Portland, Ore.

The shock index – the ratio of heart rate divided by systolic blood pressure – is a simple calculation that can help fuel or allay suspicion of septic shock, he said. A normal ratio is 0.5-0.7. A ratio of 1.0 or greater may predict uncompensated shock.

Lactate levels also help stratify patients. A lactate level greater than 2 mmol/L has been associated with increased risk of sepsis and death and indicates end-organ dysfunction, he said. Lactate levels greater than 4 mmol/L are associated with a 25% risk of death.

The second step in SAVE is to act by perfusing the patient and giving the right antibiotics.

Fill the patient’s "tank" by aggressively giving fluids in serial 500- to 1,000-mL boluses of normal saline, he said. Often, 50-60 mL/kg are needed. "The fluids are about a liter every 30 minutes, if you think you’ve got someone with severe sepsis or septic shock. Four to six liters is not unusual before you fill the tank," he said.

Early goals in perfusion should be a mean arterial pressure greater than 65 mm Hg, urine output greater than 0.5 mL/kg per hour, and signs of clinical improvement such as waking up.

Tighten the patient’s perfusion "hose" by administering pressors when the "tank" is full and central venous pressure measures 8-12 mm Hg or ultrasound assessment of the inferior vena cava (IVC) shows greater than a 50% collapse of the IVC on breathing, which is suggestive of a central venous pressure less than 8 mm Hg.

"It’s easy to take the ultrasound, slap it on the IVC. When they breathe in, if the IVC is collapsing, they need more fluid," Dr. Vissers said.

Use norepinephrine or dopamine; there’s no evidence that one pressor is better than another, he said. The perfusion goals at this point would be a mean arterial pressure less than 65 mm Hg, central venous oxygen saturation greater than 70%, and lactate clearance equivalent to central venous oxygen saturation. Greater than a 10% clearance in lactate improves the chance of survival.

Delay in antibiotics is associated with significantly higher mortality, so aim to give antibiotics within an hour of triage or diagnosis. Giving inappropriate antibiotics increases the risk of death two- to fivefold.

If the infection has an unknown source, treat with vancomycin plus piperacillin-tazobactam, ticarcillin-clavulanate, ceftriaxone, cefotaxime, imipenem, or meropenem. If the source is unknown and there’s a risk for pseudomonas infection, give three antibiotics – vancomycin plus two of the following categories: piperacillin-tazobactam or ticarcillin-clavulanate; ciprofloxacin; gentamicin; ceftazidime or cefepime; and imipenem or meropenem.

Early initiation of mechanical ventilation/oxygenation is the third part of SAVE. Septic shock makes breathing harder, which can lead to hypoxia and acidosis and produces a 50% chance of adult respiratory distress syndrome. To reduce potential lung damage, Dr. Vissers recommended these ventilator settings: a low tidal volume of 6 cc/kg of ideal body weight and plateau pressure less than 30 cm H₂O.

Last, evaluate the goals to SAVE a patient in septic shock. If lactate does not decrease by 10% or central venous oxygen saturation is less than 70% and the hemoglobin level is less than 7 g/dL, transfuse packed red blood cells. If the mean arterial pressure is less than 65 mm Hg despite optimal fluids and a pressor, consider giving IV hydrocortisone 100 mg and packed red blood cells if the hemoglobin is less than 10 g/dL. If the mean arterial pressure is greater than 65 mm Hg but the patient is still underperfused, consider giving inotropic dobutamine.

Some basic steps in the emergency department can help improve outcomes beyond the hospital, Dr. Vissers added. Elevate the head of the patient’s bed by 30-45 degrees. Decompress the stomach with an orogastric tube, and use sterile technique with any procedures.

Dr. Vissers said he has no relevant conflicts of interest.

SAN FRANCISCO – To save a patient in septic shock, think SAVE.

The acronym stands for Suspicion, Act, Ventilation/oxygenation, and Evaluate the goals, Dr. Robert J. Vissers said at the annual meeting of the American College of Emergency Physicians.

He adapted the SAVE acronym from the 2011 Critical Points continuing medical education course for emergency physicians.

Suspicion starts with recognizing systemic inflammatory response syndrome (SIRS), which combined with an infection constitutes sepsis. Patients have SIRS if they have at least two of the following: temperature higher than 38° C or below 36° C; heart rate faster than 90 beats per minute; white blood cell count over 12,000 or less than 4,000 cells/mcL or with greater than 10% bands (immature forms); and a respiratory rate over 20 breaths per minute or, on blood gas, a partial pressure of carbon dioxide less than 32 mm Hg.

Patients with sepsis and organ dysfunction, hypoperfusion, or hypotension have severe sepsis and are considered to have septic shock if the hypotension or hypoperfusion is refractory to fluid resuscitation, said Dr. Vissers, chief of emergency medicine at Legacy Emanuel Hospital, Portland, Ore.

The shock index – the ratio of heart rate divided by systolic blood pressure – is a simple calculation that can help fuel or allay suspicion of septic shock, he said. A normal ratio is 0.5-0.7. A ratio of 1.0 or greater may predict uncompensated shock.

Lactate levels also help stratify patients. A lactate level greater than 2 mmol/L has been associated with increased risk of sepsis and death and indicates end-organ dysfunction, he said. Lactate levels greater than 4 mmol/L are associated with a 25% risk of death.

The second step in SAVE is to act by perfusing the patient and giving the right antibiotics.

Fill the patient’s "tank" by aggressively giving fluids in serial 500- to 1,000-mL boluses of normal saline, he said. Often, 50-60 mL/kg are needed. "The fluids are about a liter every 30 minutes, if you think you’ve got someone with severe sepsis or septic shock. Four to six liters is not unusual before you fill the tank," he said.

Early goals in perfusion should be a mean arterial pressure greater than 65 mm Hg, urine output greater than 0.5 mL/kg per hour, and signs of clinical improvement such as waking up.

Tighten the patient’s perfusion "hose" by administering pressors when the "tank" is full and central venous pressure measures 8-12 mm Hg or ultrasound assessment of the inferior vena cava (IVC) shows greater than a 50% collapse of the IVC on breathing, which is suggestive of a central venous pressure less than 8 mm Hg.

"It’s easy to take the ultrasound, slap it on the IVC. When they breathe in, if the IVC is collapsing, they need more fluid," Dr. Vissers said.

Use norepinephrine or dopamine; there’s no evidence that one pressor is better than another, he said. The perfusion goals at this point would be a mean arterial pressure less than 65 mm Hg, central venous oxygen saturation greater than 70%, and lactate clearance equivalent to central venous oxygen saturation. Greater than a 10% clearance in lactate improves the chance of survival.

Delay in antibiotics is associated with significantly higher mortality, so aim to give antibiotics within an hour of triage or diagnosis. Giving inappropriate antibiotics increases the risk of death two- to fivefold.

If the infection has an unknown source, treat with vancomycin plus piperacillin-tazobactam, ticarcillin-clavulanate, ceftriaxone, cefotaxime, imipenem, or meropenem. If the source is unknown and there’s a risk for pseudomonas infection, give three antibiotics – vancomycin plus two of the following categories: piperacillin-tazobactam or ticarcillin-clavulanate; ciprofloxacin; gentamicin; ceftazidime or cefepime; and imipenem or meropenem.

Early initiation of mechanical ventilation/oxygenation is the third part of SAVE. Septic shock makes breathing harder, which can lead to hypoxia and acidosis and produces a 50% chance of adult respiratory distress syndrome. To reduce potential lung damage, Dr. Vissers recommended these ventilator settings: a low tidal volume of 6 cc/kg of ideal body weight and plateau pressure less than 30 cm H₂O.

Last, evaluate the goals to SAVE a patient in septic shock. If lactate does not decrease by 10% or central venous oxygen saturation is less than 70% and the hemoglobin level is less than 7 g/dL, transfuse packed red blood cells. If the mean arterial pressure is less than 65 mm Hg despite optimal fluids and a pressor, consider giving IV hydrocortisone 100 mg and packed red blood cells if the hemoglobin is less than 10 g/dL. If the mean arterial pressure is greater than 65 mm Hg but the patient is still underperfused, consider giving inotropic dobutamine.

Some basic steps in the emergency department can help improve outcomes beyond the hospital, Dr. Vissers added. Elevate the head of the patient’s bed by 30-45 degrees. Decompress the stomach with an orogastric tube, and use sterile technique with any procedures.

Dr. Vissers said he has no relevant conflicts of interest.

SAN FRANCISCO – To save a patient in septic shock, think SAVE.

The acronym stands for Suspicion, Act, Ventilation/oxygenation, and Evaluate the goals, Dr. Robert J. Vissers said at the annual meeting of the American College of Emergency Physicians.

He adapted the SAVE acronym from the 2011 Critical Points continuing medical education course for emergency physicians.

Suspicion starts with recognizing systemic inflammatory response syndrome (SIRS), which combined with an infection constitutes sepsis. Patients have SIRS if they have at least two of the following: temperature higher than 38° C or below 36° C; heart rate faster than 90 beats per minute; white blood cell count over 12,000 or less than 4,000 cells/mcL or with greater than 10% bands (immature forms); and a respiratory rate over 20 breaths per minute or, on blood gas, a partial pressure of carbon dioxide less than 32 mm Hg.

Patients with sepsis and organ dysfunction, hypoperfusion, or hypotension have severe sepsis and are considered to have septic shock if the hypotension or hypoperfusion is refractory to fluid resuscitation, said Dr. Vissers, chief of emergency medicine at Legacy Emanuel Hospital, Portland, Ore.

The shock index – the ratio of heart rate divided by systolic blood pressure – is a simple calculation that can help fuel or allay suspicion of septic shock, he said. A normal ratio is 0.5-0.7. A ratio of 1.0 or greater may predict uncompensated shock.

Lactate levels also help stratify patients. A lactate level greater than 2 mmol/L has been associated with increased risk of sepsis and death and indicates end-organ dysfunction, he said. Lactate levels greater than 4 mmol/L are associated with a 25% risk of death.

The second step in SAVE is to act by perfusing the patient and giving the right antibiotics.

Fill the patient’s "tank" by aggressively giving fluids in serial 500- to 1,000-mL boluses of normal saline, he said. Often, 50-60 mL/kg are needed. "The fluids are about a liter every 30 minutes, if you think you’ve got someone with severe sepsis or septic shock. Four to six liters is not unusual before you fill the tank," he said.

Early goals in perfusion should be a mean arterial pressure greater than 65 mm Hg, urine output greater than 0.5 mL/kg per hour, and signs of clinical improvement such as waking up.

Tighten the patient’s perfusion "hose" by administering pressors when the "tank" is full and central venous pressure measures 8-12 mm Hg or ultrasound assessment of the inferior vena cava (IVC) shows greater than a 50% collapse of the IVC on breathing, which is suggestive of a central venous pressure less than 8 mm Hg.

"It’s easy to take the ultrasound, slap it on the IVC. When they breathe in, if the IVC is collapsing, they need more fluid," Dr. Vissers said.

Use norepinephrine or dopamine; there’s no evidence that one pressor is better than another, he said. The perfusion goals at this point would be a mean arterial pressure less than 65 mm Hg, central venous oxygen saturation greater than 70%, and lactate clearance equivalent to central venous oxygen saturation. Greater than a 10% clearance in lactate improves the chance of survival.

Delay in antibiotics is associated with significantly higher mortality, so aim to give antibiotics within an hour of triage or diagnosis. Giving inappropriate antibiotics increases the risk of death two- to fivefold.

If the infection has an unknown source, treat with vancomycin plus piperacillin-tazobactam, ticarcillin-clavulanate, ceftriaxone, cefotaxime, imipenem, or meropenem. If the source is unknown and there’s a risk for pseudomonas infection, give three antibiotics – vancomycin plus two of the following categories: piperacillin-tazobactam or ticarcillin-clavulanate; ciprofloxacin; gentamicin; ceftazidime or cefepime; and imipenem or meropenem.

Early initiation of mechanical ventilation/oxygenation is the third part of SAVE. Septic shock makes breathing harder, which can lead to hypoxia and acidosis and produces a 50% chance of adult respiratory distress syndrome. To reduce potential lung damage, Dr. Vissers recommended these ventilator settings: a low tidal volume of 6 cc/kg of ideal body weight and plateau pressure less than 30 cm H₂O.

Last, evaluate the goals to SAVE a patient in septic shock. If lactate does not decrease by 10% or central venous oxygen saturation is less than 70% and the hemoglobin level is less than 7 g/dL, transfuse packed red blood cells. If the mean arterial pressure is less than 65 mm Hg despite optimal fluids and a pressor, consider giving IV hydrocortisone 100 mg and packed red blood cells if the hemoglobin is less than 10 g/dL. If the mean arterial pressure is greater than 65 mm Hg but the patient is still underperfused, consider giving inotropic dobutamine.

Some basic steps in the emergency department can help improve outcomes beyond the hospital, Dr. Vissers added. Elevate the head of the patient’s bed by 30-45 degrees. Decompress the stomach with an orogastric tube, and use sterile technique with any procedures.

Dr. Vissers said he has no relevant conflicts of interest.

SAN FRANCISCO – Rapidly lowering blood pressure in patients who are having a hypertensive emergency or hypertensive urgency isn’t necessary and may be harmful, except in the case of aortic dissection.

Lower blood pressure gradually in the emergency department to maintain cerebral perfusion within acceptable limits, Dr. Michael J. Bresler advised at the annual meeting of the American College of Emergency Physicians. For most patients, don’t push diastolic blood pressure down below 110 mm Hg, he added.

Hypertensive emergencies should be treated with IV medications, said Dr. Bresler of Stanford (Calif.) University. It’s not an emergency unless acute high blood pressure is causing end-organ damage, usually to the brain, heart, or kidneys. Blood pressure usually measures above 220 mm Hg systolic or 130 mm Hg diastolic in hypertensive emergencies.

Hypertensive urgency consists of blood pressure greater than 220 mm Hg systolic or 120 mm Hg diastolic but without acute organ failure or acute symptoms directly attributable to the blood pressure elevation. Physicians may opt to treat hypertensive urgency with oral medications in the ED, but usually the patient gets a prescription for outpatient therapy, he said.

Patients with elevated blood pressure greater than 140 mm Hg systolic or 90 mm Hg diastolic do not have urgent or emergent hypertension, but should be referred for further evaluation. Physicians may choose to write a prescription for outpatient antihypertensive therapy, but treatment in the ED is not warranted, Dr. Bresler said.

"It’s not the numbers that count" in assessing hypertension in the ED, he said. "It’s whether the patient has an acute problem from the blood pressure."

When choosing antihypertensive therapy, some medications are more suitable for the ED than are others.

The most commonly used antihypertensive in emergency medicine is nitroprusside, a parenteral vasodilator that’s very effective and has a very short half-life. The drug has disadvantages, however. It’s unstable in UV light, and so must be wrapped, and it metabolizes to cyanide/thiocyanate. Nitroprusside can cause orthostatic hypotension, is toxic at higher doses and potentially toxic to fetuses, increases intracranial pressure, and can cause tissue necrosis if there’s extravasation.

Nitroglycerin, another parenteral vasodilator, is good for patients with heart failure and angina, but it’s not a good drug for hypertensive crisis, Dr. Bresler said.

Among calcium channel blockers, the most useful for blood pressure control in the emergency department are IV nicardipine or IV clevidipine. These drugs are as effective as nitroprusside without the cyanide/thiocyanate toxicity. They are not light sensitive and so don’t need a foil wrap. Rate adjustments are required about a third as often as with nitroprusside. The IV calcium channel blockers don’t need an arterial line and don’t cause intracerebral vasodilation, which can lead to edema.

"Many of us are switching to nicardipine instead of nitroprusside," Dr. Bresler said.

Among beta-blockers, his top picks for emergency medicine are IV labetalol (which also is an alpha-blocker), oral or IV metoprolol, or IV esmolol, a short-acting cardioselective agent. In patients with coronary artery disease or with anxiety, beta-blockers are a good choice, he said. For oral therapy, the long-acting preparations are best.

ACE inhibitors are especially helpful for hypertension in patients with diabetes, renal failure, or heart failure. The most useful for emergency departments is IV enalapril, he said. But 1 in 2,000 patients who are treated with an ACE inhibitor will develop angioedema, and 1 in 10 will develop cough.

Angiotension II receptor blockers (ARBs) such as losartan, valsartan, or irbesartan are as effective as ACE inhibitors and have fewer side effects. Angioedema is rare, and the drugs do not cause cough. "I think as these become generic, they will replace ACE inhibitors," Dr. Bresler said.

Like ARBs, direct renin inhibitors such as aliskiren are similar in efficacy to ACE inhibitors with fewer side effects.

Hypertensive urgency also could be treated with oral clonidine, an alpha₂ adrenergic agonist.

Diuretics have no role in treating high blood pressure in the ED, but are a mainstay of outpatient therapy, he said. Diuretics are inexpensive and are at least as effective as ACE inhibitors or calcium channel blockers, but most hypertensive patients will require other medications in addition to diuretics.

Dr. Bresler said he has no relevant conflicts of interest.

SAN FRANCISCO – Rapidly lowering blood pressure in patients who are having a hypertensive emergency or hypertensive urgency isn’t necessary and may be harmful, except in the case of aortic dissection.

Lower blood pressure gradually in the emergency department to maintain cerebral perfusion within acceptable limits, Dr. Michael J. Bresler advised at the annual meeting of the American College of Emergency Physicians. For most patients, don’t push diastolic blood pressure down below 110 mm Hg, he added.

Hypertensive emergencies should be treated with IV medications, said Dr. Bresler of Stanford (Calif.) University. It’s not an emergency unless acute high blood pressure is causing end-organ damage, usually to the brain, heart, or kidneys. Blood pressure usually measures above 220 mm Hg systolic or 130 mm Hg diastolic in hypertensive emergencies.

Hypertensive urgency consists of blood pressure greater than 220 mm Hg systolic or 120 mm Hg diastolic but without acute organ failure or acute symptoms directly attributable to the blood pressure elevation. Physicians may opt to treat hypertensive urgency with oral medications in the ED, but usually the patient gets a prescription for outpatient therapy, he said.

Patients with elevated blood pressure greater than 140 mm Hg systolic or 90 mm Hg diastolic do not have urgent or emergent hypertension, but should be referred for further evaluation. Physicians may choose to write a prescription for outpatient antihypertensive therapy, but treatment in the ED is not warranted, Dr. Bresler said.

"It’s not the numbers that count" in assessing hypertension in the ED, he said. "It’s whether the patient has an acute problem from the blood pressure."

When choosing antihypertensive therapy, some medications are more suitable for the ED than are others.

The most commonly used antihypertensive in emergency medicine is nitroprusside, a parenteral vasodilator that’s very effective and has a very short half-life. The drug has disadvantages, however. It’s unstable in UV light, and so must be wrapped, and it metabolizes to cyanide/thiocyanate. Nitroprusside can cause orthostatic hypotension, is toxic at higher doses and potentially toxic to fetuses, increases intracranial pressure, and can cause tissue necrosis if there’s extravasation.

Nitroglycerin, another parenteral vasodilator, is good for patients with heart failure and angina, but it’s not a good drug for hypertensive crisis, Dr. Bresler said.

Among calcium channel blockers, the most useful for blood pressure control in the emergency department are IV nicardipine or IV clevidipine. These drugs are as effective as nitroprusside without the cyanide/thiocyanate toxicity. They are not light sensitive and so don’t need a foil wrap. Rate adjustments are required about a third as often as with nitroprusside. The IV calcium channel blockers don’t need an arterial line and don’t cause intracerebral vasodilation, which can lead to edema.

"Many of us are switching to nicardipine instead of nitroprusside," Dr. Bresler said.

Among beta-blockers, his top picks for emergency medicine are IV labetalol (which also is an alpha-blocker), oral or IV metoprolol, or IV esmolol, a short-acting cardioselective agent. In patients with coronary artery disease or with anxiety, beta-blockers are a good choice, he said. For oral therapy, the long-acting preparations are best.

ACE inhibitors are especially helpful for hypertension in patients with diabetes, renal failure, or heart failure. The most useful for emergency departments is IV enalapril, he said. But 1 in 2,000 patients who are treated with an ACE inhibitor will develop angioedema, and 1 in 10 will develop cough.

Angiotension II receptor blockers (ARBs) such as losartan, valsartan, or irbesartan are as effective as ACE inhibitors and have fewer side effects. Angioedema is rare, and the drugs do not cause cough. "I think as these become generic, they will replace ACE inhibitors," Dr. Bresler said.

Like ARBs, direct renin inhibitors such as aliskiren are similar in efficacy to ACE inhibitors with fewer side effects.

Hypertensive urgency also could be treated with oral clonidine, an alpha₂ adrenergic agonist.

Diuretics have no role in treating high blood pressure in the ED, but are a mainstay of outpatient therapy, he said. Diuretics are inexpensive and are at least as effective as ACE inhibitors or calcium channel blockers, but most hypertensive patients will require other medications in addition to diuretics.

Dr. Bresler said he has no relevant conflicts of interest.

SAN FRANCISCO – Rapidly lowering blood pressure in patients who are having a hypertensive emergency or hypertensive urgency isn’t necessary and may be harmful, except in the case of aortic dissection.

Lower blood pressure gradually in the emergency department to maintain cerebral perfusion within acceptable limits, Dr. Michael J. Bresler advised at the annual meeting of the American College of Emergency Physicians. For most patients, don’t push diastolic blood pressure down below 110 mm Hg, he added.

Hypertensive emergencies should be treated with IV medications, said Dr. Bresler of Stanford (Calif.) University. It’s not an emergency unless acute high blood pressure is causing end-organ damage, usually to the brain, heart, or kidneys. Blood pressure usually measures above 220 mm Hg systolic or 130 mm Hg diastolic in hypertensive emergencies.

Hypertensive urgency consists of blood pressure greater than 220 mm Hg systolic or 120 mm Hg diastolic but without acute organ failure or acute symptoms directly attributable to the blood pressure elevation. Physicians may opt to treat hypertensive urgency with oral medications in the ED, but usually the patient gets a prescription for outpatient therapy, he said.

Patients with elevated blood pressure greater than 140 mm Hg systolic or 90 mm Hg diastolic do not have urgent or emergent hypertension, but should be referred for further evaluation. Physicians may choose to write a prescription for outpatient antihypertensive therapy, but treatment in the ED is not warranted, Dr. Bresler said.

"It’s not the numbers that count" in assessing hypertension in the ED, he said. "It’s whether the patient has an acute problem from the blood pressure."

When choosing antihypertensive therapy, some medications are more suitable for the ED than are others.

The most commonly used antihypertensive in emergency medicine is nitroprusside, a parenteral vasodilator that’s very effective and has a very short half-life. The drug has disadvantages, however. It’s unstable in UV light, and so must be wrapped, and it metabolizes to cyanide/thiocyanate. Nitroprusside can cause orthostatic hypotension, is toxic at higher doses and potentially toxic to fetuses, increases intracranial pressure, and can cause tissue necrosis if there’s extravasation.

Nitroglycerin, another parenteral vasodilator, is good for patients with heart failure and angina, but it’s not a good drug for hypertensive crisis, Dr. Bresler said.

Among calcium channel blockers, the most useful for blood pressure control in the emergency department are IV nicardipine or IV clevidipine. These drugs are as effective as nitroprusside without the cyanide/thiocyanate toxicity. They are not light sensitive and so don’t need a foil wrap. Rate adjustments are required about a third as often as with nitroprusside. The IV calcium channel blockers don’t need an arterial line and don’t cause intracerebral vasodilation, which can lead to edema.

"Many of us are switching to nicardipine instead of nitroprusside," Dr. Bresler said.

Among beta-blockers, his top picks for emergency medicine are IV labetalol (which also is an alpha-blocker), oral or IV metoprolol, or IV esmolol, a short-acting cardioselective agent. In patients with coronary artery disease or with anxiety, beta-blockers are a good choice, he said. For oral therapy, the long-acting preparations are best.

ACE inhibitors are especially helpful for hypertension in patients with diabetes, renal failure, or heart failure. The most useful for emergency departments is IV enalapril, he said. But 1 in 2,000 patients who are treated with an ACE inhibitor will develop angioedema, and 1 in 10 will develop cough.

Angiotension II receptor blockers (ARBs) such as losartan, valsartan, or irbesartan are as effective as ACE inhibitors and have fewer side effects. Angioedema is rare, and the drugs do not cause cough. "I think as these become generic, they will replace ACE inhibitors," Dr. Bresler said.

Like ARBs, direct renin inhibitors such as aliskiren are similar in efficacy to ACE inhibitors with fewer side effects.

Hypertensive urgency also could be treated with oral clonidine, an alpha₂ adrenergic agonist.

Diuretics have no role in treating high blood pressure in the ED, but are a mainstay of outpatient therapy, he said. Diuretics are inexpensive and are at least as effective as ACE inhibitors or calcium channel blockers, but most hypertensive patients will require other medications in addition to diuretics.

Dr. Bresler said he has no relevant conflicts of interest.

SAN FRANCISCO – Treating in-stent restenosis in patients with drug-eluting stents by using drug-eluting balloon angioplasty limited late lumen loss at 6 months to 0.43 mm instead of 1.03 mm with plain angioplasty in a randomized trial of 110 patients.

PEPCAD (Treatment of DES-In-Stent Restenosis With SeQuent Please Paclitaxel Eluting PTCA Catheter) – a multicenter, single-blind study – randomized 72 patients at seven centers to paclitaxel-coated balloon angioplasty (PCBA) using the SeQuent Please system and 38 patients to plain old balloon angioplasty (POBA), followed by 3 months of dual-antiplatelet therapy. The length of the balloon overlapped the stenotic segment by at least 2 mm at the proximal and distal margins in both groups.

With follow-up on 100% of patients in the first 6 months of the 3-year study, the minimum lumen diameters in the PCBA group were 1.75 mm in the target lesion and 1.65 in the total segment, compared with 1.10 mm and 1 mm, respectively, in the POBA group, Dr. Harald Rittger reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

The percentage of angiographic restenosis at 6 months was 17% in both the target lesion and the total segment in the PCBA group, compared with 58% in-lesion restenosis and 61% total segment restenosis in the POBA group, said Dr. Rittger of the University of Erlangen, Germany.

These differences between the groups were statistically significant.

The PCBA group also had a significantly lower rate of major adverse cardiovascular events, comprising a combination of target lesion revascularization, MI attributable to the target vessel, and cardiac death. Rates of major adverse cardiovascular events were 17% with PCBA and 50% with POBA. This difference seemed to be driven primarily by a lower rate of target lesion revascularization in the PCBA group (15%), compared with the POBA group (37%), he said.

The study included patients with lesions in native coronary arteries; restenosis in stents eluting sirolimus, everolimus or paclitaxel; and indications for percutaneous coronary intervention. They had reference vessel diameters of 2.5-3.5 mm at enrollment and lesion lengths up to 22 mm.

Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center commented, "With the increased dissemination of drug-eluting stents [DES] and less use of bare-metal stents [BMS], the in-stent restenosis we’re going to see in the future is going to be DES in-stent restenosis. I think that’s why this study is important – to see if this is a good therapy for DES restenosis. I would say these are modest results, and there is room for improvement."

Paclitaxel-coated balloon angioplasty previously has been shown to be superior to POBA and noninferior to implanting a paclitaxel-eluting stent to treat in-stent restenosis in BMS.

The results of the current study showed poorer results in treating DES in-stent restenosis, compared with studies treating BMS in-stent restenosis using paclitaxel-coated balloon angioplasty, Dr. Waksman noted. "So, either this is more difficult to treat, or this is not sufficient treatment for this."

Dr. Rittger said that the difference in results might be due to different populations being treated. Patients with DES in-stent restenosis are more complex patients and are more likely to have multiple stent layers. Half of the current cohort had more than one stent layer. The patient with the most had four stent layers.

Treating in-stent restenosis by implanting an additional stent adds another layer of metal within the coronary arteries, reducing the physiologic vasoreactivity of the vessel.

A subgroup analysis is underway to see if the drug-eluting balloon angioplasty worked better to treat in-stent restenosis in patients with one drug-eluting stent, compared with others.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, New York, commented, "It’s nice to have a choice of using drug-coated balloons for in-stent restenosis, especially when you’re dealing with multiple layers. I’d like to hear about patterns of restenosis. If these are all focal restenoses, I’m not too thrilled about the binary restenosis rates and the clinical outcomes."

Dr. Rittger said the restenoses were focal in about 80% of cases.

The study excluded patients with acute MI, chronic total occlusions, lesions in bypass grafts or bifurcations, multiple lesions in the target vessel, left main lesions, in-stent restenosis in bare-metal stents, or contraindications to aspirin or clopidogrel therapy.

Even though drug-eluting stents decrease the risk of restenosis, the incidence of in-stent restenosis has remained high because more people are getting drug-eluting stents, Dr. Rittger said.

The study was funded by B. Braun Melsungen Vascular Systems, which makes the SeQuent Please paclitaxel-coated balloon system. Dr. Waksman said he has no relevant conflicts of interest. Dr. Rittger has received fees for consulting, speaking or honoraria from B. Braun and from Siemens Medical Solutions. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, the Medicines Co., AstraZeneca, and Ortho-McNeil.

SAN FRANCISCO – Treating in-stent restenosis in patients with drug-eluting stents by using drug-eluting balloon angioplasty limited late lumen loss at 6 months to 0.43 mm instead of 1.03 mm with plain angioplasty in a randomized trial of 110 patients.

PEPCAD (Treatment of DES-In-Stent Restenosis With SeQuent Please Paclitaxel Eluting PTCA Catheter) – a multicenter, single-blind study – randomized 72 patients at seven centers to paclitaxel-coated balloon angioplasty (PCBA) using the SeQuent Please system and 38 patients to plain old balloon angioplasty (POBA), followed by 3 months of dual-antiplatelet therapy. The length of the balloon overlapped the stenotic segment by at least 2 mm at the proximal and distal margins in both groups.

With follow-up on 100% of patients in the first 6 months of the 3-year study, the minimum lumen diameters in the PCBA group were 1.75 mm in the target lesion and 1.65 in the total segment, compared with 1.10 mm and 1 mm, respectively, in the POBA group, Dr. Harald Rittger reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

The percentage of angiographic restenosis at 6 months was 17% in both the target lesion and the total segment in the PCBA group, compared with 58% in-lesion restenosis and 61% total segment restenosis in the POBA group, said Dr. Rittger of the University of Erlangen, Germany.

These differences between the groups were statistically significant.

The PCBA group also had a significantly lower rate of major adverse cardiovascular events, comprising a combination of target lesion revascularization, MI attributable to the target vessel, and cardiac death. Rates of major adverse cardiovascular events were 17% with PCBA and 50% with POBA. This difference seemed to be driven primarily by a lower rate of target lesion revascularization in the PCBA group (15%), compared with the POBA group (37%), he said.

The study included patients with lesions in native coronary arteries; restenosis in stents eluting sirolimus, everolimus or paclitaxel; and indications for percutaneous coronary intervention. They had reference vessel diameters of 2.5-3.5 mm at enrollment and lesion lengths up to 22 mm.

Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center commented, "With the increased dissemination of drug-eluting stents [DES] and less use of bare-metal stents [BMS], the in-stent restenosis we’re going to see in the future is going to be DES in-stent restenosis. I think that’s why this study is important – to see if this is a good therapy for DES restenosis. I would say these are modest results, and there is room for improvement."

Paclitaxel-coated balloon angioplasty previously has been shown to be superior to POBA and noninferior to implanting a paclitaxel-eluting stent to treat in-stent restenosis in BMS.

The results of the current study showed poorer results in treating DES in-stent restenosis, compared with studies treating BMS in-stent restenosis using paclitaxel-coated balloon angioplasty, Dr. Waksman noted. "So, either this is more difficult to treat, or this is not sufficient treatment for this."

Dr. Rittger said that the difference in results might be due to different populations being treated. Patients with DES in-stent restenosis are more complex patients and are more likely to have multiple stent layers. Half of the current cohort had more than one stent layer. The patient with the most had four stent layers.

Treating in-stent restenosis by implanting an additional stent adds another layer of metal within the coronary arteries, reducing the physiologic vasoreactivity of the vessel.

A subgroup analysis is underway to see if the drug-eluting balloon angioplasty worked better to treat in-stent restenosis in patients with one drug-eluting stent, compared with others.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, New York, commented, "It’s nice to have a choice of using drug-coated balloons for in-stent restenosis, especially when you’re dealing with multiple layers. I’d like to hear about patterns of restenosis. If these are all focal restenoses, I’m not too thrilled about the binary restenosis rates and the clinical outcomes."

Dr. Rittger said the restenoses were focal in about 80% of cases.

The study excluded patients with acute MI, chronic total occlusions, lesions in bypass grafts or bifurcations, multiple lesions in the target vessel, left main lesions, in-stent restenosis in bare-metal stents, or contraindications to aspirin or clopidogrel therapy.

Even though drug-eluting stents decrease the risk of restenosis, the incidence of in-stent restenosis has remained high because more people are getting drug-eluting stents, Dr. Rittger said.

The study was funded by B. Braun Melsungen Vascular Systems, which makes the SeQuent Please paclitaxel-coated balloon system. Dr. Waksman said he has no relevant conflicts of interest. Dr. Rittger has received fees for consulting, speaking or honoraria from B. Braun and from Siemens Medical Solutions. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, the Medicines Co., AstraZeneca, and Ortho-McNeil.

SAN FRANCISCO – Treating in-stent restenosis in patients with drug-eluting stents by using drug-eluting balloon angioplasty limited late lumen loss at 6 months to 0.43 mm instead of 1.03 mm with plain angioplasty in a randomized trial of 110 patients.

PEPCAD (Treatment of DES-In-Stent Restenosis With SeQuent Please Paclitaxel Eluting PTCA Catheter) – a multicenter, single-blind study – randomized 72 patients at seven centers to paclitaxel-coated balloon angioplasty (PCBA) using the SeQuent Please system and 38 patients to plain old balloon angioplasty (POBA), followed by 3 months of dual-antiplatelet therapy. The length of the balloon overlapped the stenotic segment by at least 2 mm at the proximal and distal margins in both groups.

With follow-up on 100% of patients in the first 6 months of the 3-year study, the minimum lumen diameters in the PCBA group were 1.75 mm in the target lesion and 1.65 in the total segment, compared with 1.10 mm and 1 mm, respectively, in the POBA group, Dr. Harald Rittger reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

The percentage of angiographic restenosis at 6 months was 17% in both the target lesion and the total segment in the PCBA group, compared with 58% in-lesion restenosis and 61% total segment restenosis in the POBA group, said Dr. Rittger of the University of Erlangen, Germany.

These differences between the groups were statistically significant.

The PCBA group also had a significantly lower rate of major adverse cardiovascular events, comprising a combination of target lesion revascularization, MI attributable to the target vessel, and cardiac death. Rates of major adverse cardiovascular events were 17% with PCBA and 50% with POBA. This difference seemed to be driven primarily by a lower rate of target lesion revascularization in the PCBA group (15%), compared with the POBA group (37%), he said.

The study included patients with lesions in native coronary arteries; restenosis in stents eluting sirolimus, everolimus or paclitaxel; and indications for percutaneous coronary intervention. They had reference vessel diameters of 2.5-3.5 mm at enrollment and lesion lengths up to 22 mm.

Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center commented, "With the increased dissemination of drug-eluting stents [DES] and less use of bare-metal stents [BMS], the in-stent restenosis we’re going to see in the future is going to be DES in-stent restenosis. I think that’s why this study is important – to see if this is a good therapy for DES restenosis. I would say these are modest results, and there is room for improvement."

Paclitaxel-coated balloon angioplasty previously has been shown to be superior to POBA and noninferior to implanting a paclitaxel-eluting stent to treat in-stent restenosis in BMS.

The results of the current study showed poorer results in treating DES in-stent restenosis, compared with studies treating BMS in-stent restenosis using paclitaxel-coated balloon angioplasty, Dr. Waksman noted. "So, either this is more difficult to treat, or this is not sufficient treatment for this."

Dr. Rittger said that the difference in results might be due to different populations being treated. Patients with DES in-stent restenosis are more complex patients and are more likely to have multiple stent layers. Half of the current cohort had more than one stent layer. The patient with the most had four stent layers.

Treating in-stent restenosis by implanting an additional stent adds another layer of metal within the coronary arteries, reducing the physiologic vasoreactivity of the vessel.

A subgroup analysis is underway to see if the drug-eluting balloon angioplasty worked better to treat in-stent restenosis in patients with one drug-eluting stent, compared with others.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, New York, commented, "It’s nice to have a choice of using drug-coated balloons for in-stent restenosis, especially when you’re dealing with multiple layers. I’d like to hear about patterns of restenosis. If these are all focal restenoses, I’m not too thrilled about the binary restenosis rates and the clinical outcomes."

Dr. Rittger said the restenoses were focal in about 80% of cases.

The study excluded patients with acute MI, chronic total occlusions, lesions in bypass grafts or bifurcations, multiple lesions in the target vessel, left main lesions, in-stent restenosis in bare-metal stents, or contraindications to aspirin or clopidogrel therapy.

Even though drug-eluting stents decrease the risk of restenosis, the incidence of in-stent restenosis has remained high because more people are getting drug-eluting stents, Dr. Rittger said.

The study was funded by B. Braun Melsungen Vascular Systems, which makes the SeQuent Please paclitaxel-coated balloon system. Dr. Waksman said he has no relevant conflicts of interest. Dr. Rittger has received fees for consulting, speaking or honoraria from B. Braun and from Siemens Medical Solutions. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, the Medicines Co., AstraZeneca, and Ortho-McNeil.

SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.

The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.

Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.

At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.

Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.

At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.

"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."

The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.

The study was not powered to detect differences in clinical events.

Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.

Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.

Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.

More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.

The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.

Baseline demographics and procedural characteristics were similar between treatment groups.

An "element of chance" was introduced in baseline lesion characteristics, with the half-dose Synergy group showing statistically significantly larger reference vessel diameters, averaging 2.65 mm, compared with 2.53 mm in the Promus Element group, Dr. Meredith said. Postprocedure angiography showed significantly greater in-stent and in-segment minimal lumen diameter, acute in-stent and in-segment gain, and in-segment stenosis diameter in the half-dose Synergy group, compared with the Promus Element group. "Again, most likely a play of chance," Dr. Meredith said.

The study was funded by Boston Scientific Corp., which makes all the stents used in the study. Dr. Meredith has been a consultant to Boston Scientific and Medtronic CardioVascular. One of his coinvestigators has received research funding from Boston Scientific and two other companies. Dr. Waksman said he has no relevant conflicts of interest. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, The Medicines Company, AstraZeneca, and Ortho-McNeil.*

*This story was updated November 12, 2011.

SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.

The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.

Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.

At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.

Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.

At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.

"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."

The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.

The study was not powered to detect differences in clinical events.

Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.

Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.

Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.

More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.

The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.

Baseline demographics and procedural characteristics were similar between treatment groups.

An "element of chance" was introduced in baseline lesion characteristics, with the half-dose Synergy group showing statistically significantly larger reference vessel diameters, averaging 2.65 mm, compared with 2.53 mm in the Promus Element group, Dr. Meredith said. Postprocedure angiography showed significantly greater in-stent and in-segment minimal lumen diameter, acute in-stent and in-segment gain, and in-segment stenosis diameter in the half-dose Synergy group, compared with the Promus Element group. "Again, most likely a play of chance," Dr. Meredith said.

The study was funded by Boston Scientific Corp., which makes all the stents used in the study. Dr. Meredith has been a consultant to Boston Scientific and Medtronic CardioVascular. One of his coinvestigators has received research funding from Boston Scientific and two other companies. Dr. Waksman said he has no relevant conflicts of interest. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, The Medicines Company, AstraZeneca, and Ortho-McNeil.*

*This story was updated November 12, 2011.

SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.

The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.

Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.

At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.

Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.

At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.

"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."

The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.

The study was not powered to detect differences in clinical events.

Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.

Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.

Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.

Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.

More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.

The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.

Baseline demographics and procedural characteristics were similar between treatment groups.

An "element of chance" was introduced in baseline lesion characteristics, with the half-dose Synergy group showing statistically significantly larger reference vessel diameters, averaging 2.65 mm, compared with 2.53 mm in the Promus Element group, Dr. Meredith said. Postprocedure angiography showed significantly greater in-stent and in-segment minimal lumen diameter, acute in-stent and in-segment gain, and in-segment stenosis diameter in the half-dose Synergy group, compared with the Promus Element group. "Again, most likely a play of chance," Dr. Meredith said.

The study was funded by Boston Scientific Corp., which makes all the stents used in the study. Dr. Meredith has been a consultant to Boston Scientific and Medtronic CardioVascular. One of his coinvestigators has received research funding from Boston Scientific and two other companies. Dr. Waksman said he has no relevant conflicts of interest. Dr. Mehran has received honoraria or funds for consulting, speaking, or research from Bristol-Myers Squibb, The Medicines Company, AstraZeneca, and Ortho-McNeil.*

*This story was updated November 12, 2011.

SAN FRANCISCO – The alphabet is changing for critical care of patients in cardiac arrest.

"A is for airway" is no longer at the top of the list. The ABCs (airway, breathing, and circulation) of cardiopulmonary resuscitation have been replaced by an emphasis on CAB – compressions, airway, and breathing, in that order.

The American Heart Association promotes the "CPR is as easy as C-A-B" slogan, and the key to success in treating cardiac arrest is high-quality, uninterrupted chest compressions, Dr. Robert J. Vissers said at the annual meeting of the American College of Emergency Physicians.

"Airway may not always come first" if the patient has lost perfusion and circulation, said Dr. Vissers, chief of emergency medicine at Legacy Emanuel Medical Center, Portland, Ore. "It’s hard for me to say, because I’m an airway guy."

While "C" stands for compressions, it also serves to remind physicians to attend to cardioversion, capnography, cooling, and catheterization, if needed. Dr. Vissers addressed each of these in more detail. "These are the things that recently have led to pretty substantial improvements in the outcomes of these patients," he said.

Compressions. With high-quality, uninterrupted chest compressions, the patient gets good passive ventilation, which may be superior to positive pressure ventilation in these situations. Aim for 30 compressions per breath. Consider creating a supraglottic airway without interrupting the CPR, he said.

Put some muscle into it to maintain compressions 2 inches in depth with full recoil, at a rate of 100 compressions per minute. If more than one person is available, take turns applying compressions to reduce fatigue. Monitor the patient closely with end-tidal capnography. (See below.)

Proper compressions restore cerebral and coronary perfusion. Sustained coronary perfusion pressure is critical to successful defibrillation.

Cardioversion. The first 4 minutes after cardiac arrest provide the greatest chance of successful cardioversion (defibrillation). If more than 4 minutes have elapsed, reperfuse the myocardium with a few minutes of chest compressions before applying shock. Wait 2 minutes after defibrillation to check the pulse, and maintain compressions during that time.

The traditional admonition to "clear!" before shocking may not be necessary, Dr. Vissers said. Studies have shown that no appreciable electrical current reaches the people applying compressions if they are wearing gloves and a biphasic defibrillator is used for cardioversion.

Capnography. Confirm proper tube placement for capnography, which helps assess the quality of the CPR and identify return of spontaneous circulation without checking pulses. Capnography readings also help predict outcome.

"I think capnography is one of the most underutilized tools that we have for the critically ill patient," Dr. Vissers said.

High-quality compressions and coronary perfusion pressures correlate with end-tidal carbon dioxide (ETCO₂) levels of 20-25 mm Hg on capnography. A sudden rise in ETCO₂ suggests return of spontaneous circulation and is more sensitive than manual pulse checks. If ETCO₂ readings persistently stay below 10 mm Hg, return of spontaneous circulation is unlikely. In studies, an ETCO₂ less than 10 mm Hg after 20 minutes of compressions was associated with zero chance of return of spontaneous circulation.

Cooling. For unconscious adults who went into cardiac arrest outside of hospital care, cooling the body to 32-34° C for 12-24 hours improves chances of a good outcome, Dr. Vissers said. Applying ice packs to the groin, axilla, and neck will cool the body about 0.2-1° C per hour. The best cooling method may be cooling blankets that circulate cooled water through material designed to promote heat exchange. The blankets cool a body on average by 1-1.5° C per hour.

Used in combination, the ice packs can be removed when the body temperature reaches 33° C and the blankets left on to maintain the cool temperature for 12-24 hours. "That works very well," he said. Cooled normal saline infusions or cooling catheters also are options for cooling a body after cardiac arrest.

Of every 4-13 patients cooled after cardiac arrest, 1 will leave the hospital neurologically intact, he said.

Catheterization. Early percutaneous coronary intervention benefits patients with cardiac arrest, even those without ST-segment elevation MI, studies suggest. Consider transferring the patient for cardiac catheterization. It’s okay to cool the body and then transfer for catheterization. This may become a more common model as care after cardiac arrest becomes more regionalized, he said.

Dr. Vissers said he has no relevant conflicts of interest.

SAN FRANCISCO – The alphabet is changing for critical care of patients in cardiac arrest.

"A is for airway" is no longer at the top of the list. The ABCs (airway, breathing, and circulation) of cardiopulmonary resuscitation have been replaced by an emphasis on CAB – compressions, airway, and breathing, in that order.

The American Heart Association promotes the "CPR is as easy as C-A-B" slogan, and the key to success in treating cardiac arrest is high-quality, uninterrupted chest compressions, Dr. Robert J. Vissers said at the annual meeting of the American College of Emergency Physicians.

"Airway may not always come first" if the patient has lost perfusion and circulation, said Dr. Vissers, chief of emergency medicine at Legacy Emanuel Medical Center, Portland, Ore. "It’s hard for me to say, because I’m an airway guy."

While "C" stands for compressions, it also serves to remind physicians to attend to cardioversion, capnography, cooling, and catheterization, if needed. Dr. Vissers addressed each of these in more detail. "These are the things that recently have led to pretty substantial improvements in the outcomes of these patients," he said.

Compressions. With high-quality, uninterrupted chest compressions, the patient gets good passive ventilation, which may be superior to positive pressure ventilation in these situations. Aim for 30 compressions per breath. Consider creating a supraglottic airway without interrupting the CPR, he said.

Put some muscle into it to maintain compressions 2 inches in depth with full recoil, at a rate of 100 compressions per minute. If more than one person is available, take turns applying compressions to reduce fatigue. Monitor the patient closely with end-tidal capnography. (See below.)

Proper compressions restore cerebral and coronary perfusion. Sustained coronary perfusion pressure is critical to successful defibrillation.

Cardioversion. The first 4 minutes after cardiac arrest provide the greatest chance of successful cardioversion (defibrillation). If more than 4 minutes have elapsed, reperfuse the myocardium with a few minutes of chest compressions before applying shock. Wait 2 minutes after defibrillation to check the pulse, and maintain compressions during that time.

The traditional admonition to "clear!" before shocking may not be necessary, Dr. Vissers said. Studies have shown that no appreciable electrical current reaches the people applying compressions if they are wearing gloves and a biphasic defibrillator is used for cardioversion.

Capnography. Confirm proper tube placement for capnography, which helps assess the quality of the CPR and identify return of spontaneous circulation without checking pulses. Capnography readings also help predict outcome.

"I think capnography is one of the most underutilized tools that we have for the critically ill patient," Dr. Vissers said.

High-quality compressions and coronary perfusion pressures correlate with end-tidal carbon dioxide (ETCO₂) levels of 20-25 mm Hg on capnography. A sudden rise in ETCO₂ suggests return of spontaneous circulation and is more sensitive than manual pulse checks. If ETCO₂ readings persistently stay below 10 mm Hg, return of spontaneous circulation is unlikely. In studies, an ETCO₂ less than 10 mm Hg after 20 minutes of compressions was associated with zero chance of return of spontaneous circulation.

Cooling. For unconscious adults who went into cardiac arrest outside of hospital care, cooling the body to 32-34° C for 12-24 hours improves chances of a good outcome, Dr. Vissers said. Applying ice packs to the groin, axilla, and neck will cool the body about 0.2-1° C per hour. The best cooling method may be cooling blankets that circulate cooled water through material designed to promote heat exchange. The blankets cool a body on average by 1-1.5° C per hour.

Used in combination, the ice packs can be removed when the body temperature reaches 33° C and the blankets left on to maintain the cool temperature for 12-24 hours. "That works very well," he said. Cooled normal saline infusions or cooling catheters also are options for cooling a body after cardiac arrest.

Of every 4-13 patients cooled after cardiac arrest, 1 will leave the hospital neurologically intact, he said.

Catheterization. Early percutaneous coronary intervention benefits patients with cardiac arrest, even those without ST-segment elevation MI, studies suggest. Consider transferring the patient for cardiac catheterization. It’s okay to cool the body and then transfer for catheterization. This may become a more common model as care after cardiac arrest becomes more regionalized, he said.

Dr. Vissers said he has no relevant conflicts of interest.

SAN FRANCISCO – The alphabet is changing for critical care of patients in cardiac arrest.

"A is for airway" is no longer at the top of the list. The ABCs (airway, breathing, and circulation) of cardiopulmonary resuscitation have been replaced by an emphasis on CAB – compressions, airway, and breathing, in that order.

The American Heart Association promotes the "CPR is as easy as C-A-B" slogan, and the key to success in treating cardiac arrest is high-quality, uninterrupted chest compressions, Dr. Robert J. Vissers said at the annual meeting of the American College of Emergency Physicians.

"Airway may not always come first" if the patient has lost perfusion and circulation, said Dr. Vissers, chief of emergency medicine at Legacy Emanuel Medical Center, Portland, Ore. "It’s hard for me to say, because I’m an airway guy."

While "C" stands for compressions, it also serves to remind physicians to attend to cardioversion, capnography, cooling, and catheterization, if needed. Dr. Vissers addressed each of these in more detail. "These are the things that recently have led to pretty substantial improvements in the outcomes of these patients," he said.

Compressions. With high-quality, uninterrupted chest compressions, the patient gets good passive ventilation, which may be superior to positive pressure ventilation in these situations. Aim for 30 compressions per breath. Consider creating a supraglottic airway without interrupting the CPR, he said.

Put some muscle into it to maintain compressions 2 inches in depth with full recoil, at a rate of 100 compressions per minute. If more than one person is available, take turns applying compressions to reduce fatigue. Monitor the patient closely with end-tidal capnography. (See below.)

Proper compressions restore cerebral and coronary perfusion. Sustained coronary perfusion pressure is critical to successful defibrillation.

Cardioversion. The first 4 minutes after cardiac arrest provide the greatest chance of successful cardioversion (defibrillation). If more than 4 minutes have elapsed, reperfuse the myocardium with a few minutes of chest compressions before applying shock. Wait 2 minutes after defibrillation to check the pulse, and maintain compressions during that time.

The traditional admonition to "clear!" before shocking may not be necessary, Dr. Vissers said. Studies have shown that no appreciable electrical current reaches the people applying compressions if they are wearing gloves and a biphasic defibrillator is used for cardioversion.

Capnography. Confirm proper tube placement for capnography, which helps assess the quality of the CPR and identify return of spontaneous circulation without checking pulses. Capnography readings also help predict outcome.

"I think capnography is one of the most underutilized tools that we have for the critically ill patient," Dr. Vissers said.

High-quality compressions and coronary perfusion pressures correlate with end-tidal carbon dioxide (ETCO₂) levels of 20-25 mm Hg on capnography. A sudden rise in ETCO₂ suggests return of spontaneous circulation and is more sensitive than manual pulse checks. If ETCO₂ readings persistently stay below 10 mm Hg, return of spontaneous circulation is unlikely. In studies, an ETCO₂ less than 10 mm Hg after 20 minutes of compressions was associated with zero chance of return of spontaneous circulation.

Cooling. For unconscious adults who went into cardiac arrest outside of hospital care, cooling the body to 32-34° C for 12-24 hours improves chances of a good outcome, Dr. Vissers said. Applying ice packs to the groin, axilla, and neck will cool the body about 0.2-1° C per hour. The best cooling method may be cooling blankets that circulate cooled water through material designed to promote heat exchange. The blankets cool a body on average by 1-1.5° C per hour.

Used in combination, the ice packs can be removed when the body temperature reaches 33° C and the blankets left on to maintain the cool temperature for 12-24 hours. "That works very well," he said. Cooled normal saline infusions or cooling catheters also are options for cooling a body after cardiac arrest.

Of every 4-13 patients cooled after cardiac arrest, 1 will leave the hospital neurologically intact, he said.

Catheterization. Early percutaneous coronary intervention benefits patients with cardiac arrest, even those without ST-segment elevation MI, studies suggest. Consider transferring the patient for cardiac catheterization. It’s okay to cool the body and then transfer for catheterization. This may become a more common model as care after cardiac arrest becomes more regionalized, he said.

Dr. Vissers said he has no relevant conflicts of interest.

SAN FRANCISCO – Transradial access for angioplasty to treat ST elevation acute coronary syndrome significantly reduced the risk of morbidity and mortality by 40%, compared with a transfemoral approach in a multicenter randomized controlled trial in 1,001 patients.

In the first 30 days after treatment, 14% in the radial access group and 21% in the femoral access group met the primary composite endpoint of cardiac death, MI, stroke, target lesion revascularization, or bleeding not related to coronary artery bypass graft (CABG), Dr. Enrico Romagnoli reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

He and his associates conducted the prospective RIFLE STEACS trial (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome) at four high-volume clinical sites in Italy between January 2009 and July 2011.

Results for both the primary composite endpoint and the individual components of that endpoint showed significantly lower morbidity and mortality using the radial approach instead of the femoral approach in these patients.

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site" when treating ST elevation acute coronary syndrome (STEACS), said Dr. Romagnoli, an interventional cardiologist at Policlinico Casilino, Rome.

It’s time for U.S. interventional radiologists to catch up with the rest of the world in offering the radial approach to patients undergoing angioplasty for ST elevation acute coronary syndrome, several commentators said at a press briefing held at the meeting.

"In most parts of the world outside the United States, radial is the dominant access," noted Dr. John A. Ormiston, an interventional cardiologist at the University of Auckland (New Zealand), and medical director of Mercy Angiography, Auckland. "In our records, probably 90% of all procedures are now radial. We’re not surprised about this data. The more we hear about this, the more the U.S. has to do it."

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site."

Patients prefer the radial approach and seek treatment from physicians who offer it instead of the femoral approach, he said. "That’s one thing that will drive the U.S. change."

Dr. Pieter R. Stella of University Medical Center in Utrecht, the Netherlands, cautioned that physicians who choose the transradial approach for angioplasty should use it in all cases, not just in a select group, for the safest practices and best outcomes.

Among components of the composite endpoint in the study, rates of major adverse cardiac and cerebrovascular events were 7% in the radial group and 11% in the femoral group. Bleeding occurred in 8% of the radial group and 12% of the femoral group (Bleeding Academic Research Consortium types 2-5).

Cardiac death rates were 5% in the radial group and 9% in the femoral group. "This is the strongest message of this study," Dr. Romagnoli said.

All of these differences between groups were statistically significant.

The groups did not differ significantly in 30-day rates of MI (1.2% in the radial group vs. 1.4% in the femoral group), target lesion revascularization (1.2% vs. 1.8%, respectively), or cerebrovascular accident (0.8% vs. 0.5%, respectively).

The differences in bleeding were driven by a significantly lower rate of access site–related bleeding in the radial group (3% of patients), compared with the femoral group (7%). Rates of bleeding not related to the access site were 5% in each group.

"We all know that bleeding and hemorrhagic events are an important predictor of mortality in acute coronary syndrome. A radial approach virtually eliminates vascular access-site bleeding. Thus, the systematic use of a radial approach in patients with acute ST elevation MI – who are patients at high risk of bleeding from the aggressive antiplatelets and antithrombotics they receive – could improve the clinical outcome, in particular by reducing mortality," Dr. Romagnoli said in an interview.

In an analysis of predictors of the primary composite outcome, radial access was the only factor that significantly reduced risk, by 40%, he said. Four other factors each doubled the risk for the composite outcome: female gender; chronic kidney disease; Killip class; presence of culprit lesions in the left anterior descending coronary artery, and left ventricular ejection fraction less than 50%.

The study was sponsored by the independent investigators. Dr. Romagnoli said he had no relevant conflicts of interest. Dr. Ormiston has received honoraria or fees for consulting or speaking from Abbott Vascular and Boston Scientific Corp. Dr. Stella has received honoraria or fees for consulting or speaking from Eurocor and SMT Medical. Dr. Rao has received honoraria or fees for consulting, speaking or research from the Cordis Corp., Ikaria, the Medicines Co., Boehringer Ingelheim, Abbott Vascular, Terumo Medical Corp., and AstraZeneca.

SAN FRANCISCO – Transradial access for angioplasty to treat ST elevation acute coronary syndrome significantly reduced the risk of morbidity and mortality by 40%, compared with a transfemoral approach in a multicenter randomized controlled trial in 1,001 patients.

In the first 30 days after treatment, 14% in the radial access group and 21% in the femoral access group met the primary composite endpoint of cardiac death, MI, stroke, target lesion revascularization, or bleeding not related to coronary artery bypass graft (CABG), Dr. Enrico Romagnoli reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

He and his associates conducted the prospective RIFLE STEACS trial (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome) at four high-volume clinical sites in Italy between January 2009 and July 2011.

Results for both the primary composite endpoint and the individual components of that endpoint showed significantly lower morbidity and mortality using the radial approach instead of the femoral approach in these patients.

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site" when treating ST elevation acute coronary syndrome (STEACS), said Dr. Romagnoli, an interventional cardiologist at Policlinico Casilino, Rome.

It’s time for U.S. interventional radiologists to catch up with the rest of the world in offering the radial approach to patients undergoing angioplasty for ST elevation acute coronary syndrome, several commentators said at a press briefing held at the meeting.

"In most parts of the world outside the United States, radial is the dominant access," noted Dr. John A. Ormiston, an interventional cardiologist at the University of Auckland (New Zealand), and medical director of Mercy Angiography, Auckland. "In our records, probably 90% of all procedures are now radial. We’re not surprised about this data. The more we hear about this, the more the U.S. has to do it."

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site."

Patients prefer the radial approach and seek treatment from physicians who offer it instead of the femoral approach, he said. "That’s one thing that will drive the U.S. change."

Dr. Pieter R. Stella of University Medical Center in Utrecht, the Netherlands, cautioned that physicians who choose the transradial approach for angioplasty should use it in all cases, not just in a select group, for the safest practices and best outcomes.

Among components of the composite endpoint in the study, rates of major adverse cardiac and cerebrovascular events were 7% in the radial group and 11% in the femoral group. Bleeding occurred in 8% of the radial group and 12% of the femoral group (Bleeding Academic Research Consortium types 2-5).

Cardiac death rates were 5% in the radial group and 9% in the femoral group. "This is the strongest message of this study," Dr. Romagnoli said.

All of these differences between groups were statistically significant.

The groups did not differ significantly in 30-day rates of MI (1.2% in the radial group vs. 1.4% in the femoral group), target lesion revascularization (1.2% vs. 1.8%, respectively), or cerebrovascular accident (0.8% vs. 0.5%, respectively).

The differences in bleeding were driven by a significantly lower rate of access site–related bleeding in the radial group (3% of patients), compared with the femoral group (7%). Rates of bleeding not related to the access site were 5% in each group.

"We all know that bleeding and hemorrhagic events are an important predictor of mortality in acute coronary syndrome. A radial approach virtually eliminates vascular access-site bleeding. Thus, the systematic use of a radial approach in patients with acute ST elevation MI – who are patients at high risk of bleeding from the aggressive antiplatelets and antithrombotics they receive – could improve the clinical outcome, in particular by reducing mortality," Dr. Romagnoli said in an interview.

In an analysis of predictors of the primary composite outcome, radial access was the only factor that significantly reduced risk, by 40%, he said. Four other factors each doubled the risk for the composite outcome: female gender; chronic kidney disease; Killip class; presence of culprit lesions in the left anterior descending coronary artery, and left ventricular ejection fraction less than 50%.

The study was sponsored by the independent investigators. Dr. Romagnoli said he had no relevant conflicts of interest. Dr. Ormiston has received honoraria or fees for consulting or speaking from Abbott Vascular and Boston Scientific Corp. Dr. Stella has received honoraria or fees for consulting or speaking from Eurocor and SMT Medical. Dr. Rao has received honoraria or fees for consulting, speaking or research from the Cordis Corp., Ikaria, the Medicines Co., Boehringer Ingelheim, Abbott Vascular, Terumo Medical Corp., and AstraZeneca.

SAN FRANCISCO – Transradial access for angioplasty to treat ST elevation acute coronary syndrome significantly reduced the risk of morbidity and mortality by 40%, compared with a transfemoral approach in a multicenter randomized controlled trial in 1,001 patients.

In the first 30 days after treatment, 14% in the radial access group and 21% in the femoral access group met the primary composite endpoint of cardiac death, MI, stroke, target lesion revascularization, or bleeding not related to coronary artery bypass graft (CABG), Dr. Enrico Romagnoli reported at Transcatheter Cardiovascular Therapeutics 2011, which was sponsored by the Cardiovascular Research Foundation.

He and his associates conducted the prospective RIFLE STEACS trial (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome) at four high-volume clinical sites in Italy between January 2009 and July 2011.

Results for both the primary composite endpoint and the individual components of that endpoint showed significantly lower morbidity and mortality using the radial approach instead of the femoral approach in these patients.

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site" when treating ST elevation acute coronary syndrome (STEACS), said Dr. Romagnoli, an interventional cardiologist at Policlinico Casilino, Rome.

It’s time for U.S. interventional radiologists to catch up with the rest of the world in offering the radial approach to patients undergoing angioplasty for ST elevation acute coronary syndrome, several commentators said at a press briefing held at the meeting.

"In most parts of the world outside the United States, radial is the dominant access," noted Dr. John A. Ormiston, an interventional cardiologist at the University of Auckland (New Zealand), and medical director of Mercy Angiography, Auckland. "In our records, probably 90% of all procedures are now radial. We’re not surprised about this data. The more we hear about this, the more the U.S. has to do it."

"The radial approach should thus no more be considered a valid alternative to the femoral one, but become the recommended access site."

Patients prefer the radial approach and seek treatment from physicians who offer it instead of the femoral approach, he said. "That’s one thing that will drive the U.S. change."

Dr. Pieter R. Stella of University Medical Center in Utrecht, the Netherlands, cautioned that physicians who choose the transradial approach for angioplasty should use it in all cases, not just in a select group, for the safest practices and best outcomes.

Among components of the composite endpoint in the study, rates of major adverse cardiac and cerebrovascular events were 7% in the radial group and 11% in the femoral group. Bleeding occurred in 8% of the radial group and 12% of the femoral group (Bleeding Academic Research Consortium types 2-5).

Cardiac death rates were 5% in the radial group and 9% in the femoral group. "This is the strongest message of this study," Dr. Romagnoli said.

All of these differences between groups were statistically significant.

The groups did not differ significantly in 30-day rates of MI (1.2% in the radial group vs. 1.4% in the femoral group), target lesion revascularization (1.2% vs. 1.8%, respectively), or cerebrovascular accident (0.8% vs. 0.5%, respectively).

The differences in bleeding were driven by a significantly lower rate of access site–related bleeding in the radial group (3% of patients), compared with the femoral group (7%). Rates of bleeding not related to the access site were 5% in each group.

"We all know that bleeding and hemorrhagic events are an important predictor of mortality in acute coronary syndrome. A radial approach virtually eliminates vascular access-site bleeding. Thus, the systematic use of a radial approach in patients with acute ST elevation MI – who are patients at high risk of bleeding from the aggressive antiplatelets and antithrombotics they receive – could improve the clinical outcome, in particular by reducing mortality," Dr. Romagnoli said in an interview.

In an analysis of predictors of the primary composite outcome, radial access was the only factor that significantly reduced risk, by 40%, he said. Four other factors each doubled the risk for the composite outcome: female gender; chronic kidney disease; Killip class; presence of culprit lesions in the left anterior descending coronary artery, and left ventricular ejection fraction less than 50%.

The study was sponsored by the independent investigators. Dr. Romagnoli said he had no relevant conflicts of interest. Dr. Ormiston has received honoraria or fees for consulting or speaking from Abbott Vascular and Boston Scientific Corp. Dr. Stella has received honoraria or fees for consulting or speaking from Eurocor and SMT Medical. Dr. Rao has received honoraria or fees for consulting, speaking or research from the Cordis Corp., Ikaria, the Medicines Co., Boehringer Ingelheim, Abbott Vascular, Terumo Medical Corp., and AstraZeneca.

SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.

The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).

Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.

"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.

When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.

"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.

The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.

The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).

Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.

The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.

By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.

Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.

The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.

For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.

In explaining the risks to patients, Dr. Makkar said he would tell them that for every four patients treated with TAVI instead of standard therapy, one patient will survive. For every 12-13 patients treated with TAVI instead of standard therapy, 1 will develop a stroke.

Or, as Dr. Samir Kapadia of the Cleveland Clinic phrased it at a press briefing, patients in this population have a 50-50 chance of being alive at 2 years if they’re treated with TAVI and a 1 in 20 chance of having a stroke.

Patients in both treatment groups had a mean age of 83 years.

The hemodynamic effects of the implanted valves appeared to be stable between years 1 and 2, with sustained mean gradients and valve areas. Among patients with paravalvular leaks, 41% in each group died.

Edwards Lifesciences, which markets the Edwards Sapien valve, funded the study and was involved in its design, data collection, and monitoring. Dr. Makkar holds stock in Entourage Technologies, has received fees for consulting, speaking, or honoraria from Abbott Vascular, Medtronic and Abiomed, and has received research funds from Edwards Lifesciences. Dr. Mack and Dr. Kapadia said they have no conflicts of interest.

SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.

The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).

Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.

"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.

When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.

"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.

The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.

The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).

Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.

The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.

By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.

Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.

The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.

For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.

In explaining the risks to patients, Dr. Makkar said he would tell them that for every four patients treated with TAVI instead of standard therapy, one patient will survive. For every 12-13 patients treated with TAVI instead of standard therapy, 1 will develop a stroke.

Or, as Dr. Samir Kapadia of the Cleveland Clinic phrased it at a press briefing, patients in this population have a 50-50 chance of being alive at 2 years if they’re treated with TAVI and a 1 in 20 chance of having a stroke.

Patients in both treatment groups had a mean age of 83 years.

The hemodynamic effects of the implanted valves appeared to be stable between years 1 and 2, with sustained mean gradients and valve areas. Among patients with paravalvular leaks, 41% in each group died.

Edwards Lifesciences, which markets the Edwards Sapien valve, funded the study and was involved in its design, data collection, and monitoring. Dr. Makkar holds stock in Entourage Technologies, has received fees for consulting, speaking, or honoraria from Abbott Vascular, Medtronic and Abiomed, and has received research funds from Edwards Lifesciences. Dr. Mack and Dr. Kapadia said they have no conflicts of interest.

SAN FRANCISCO – Transcatheter aortic-valve implantation in high-risk patients with aortic stenosis who were not eligible for surgery reduced all-cause mortality at 2 years from 68% to 43%, compared with standard therapy, extending the positive 1-year results of a multicenter, randomized trial in 358 patients.

The 24% absolute reduction in risk of death means that four patients would need to be treated with transcatheter aortic-valve implantation (TAVI) to save one life at 2 years, compared with standard therapy, Dr. Raj Makkar and his associates reported on Nov. 10 at the Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The number needed to treat improved upon 1-year data presented at this meeting last year and subsequently published, which showed five patients would need to be treated to save one life at 1-year follow-up. All-cause mortality rates at 1 year were 51% on standard therapy and 31% with TAVI in the PARTNER (Placement of Aortic Transcatheter Valves) trial (N. Engl. J. Med. 2010;363:1597-1607).

Among patients who survived beyond 1 year of follow-up, all-cause mortality was halved, from 35% in the standard therapy group to 18% in the TAVI group by year 2. Overall deaths from cardiovascular causes in an intent-to-treat analysis decreased from 62% with standard therapy to 31% in the TAVI group, said Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center, Los Angeles.

"These are absolutely dramatic results. It validated and bolstered the 1-year results, an extremely positive trial," Dr. Michael Mack said at a press briefing on the study. "In this end-of-life, expensive therapy, there is a sustained benefit now out to 2 years and, hopefully, longer than that," said Dr. Mack of the Cardiopulmonary Research Science and Technology Institute, Dallas. Dr. Mack is also president of the Society of Thoracic Surgeons.

When deaths were stratified by Society of Thoracic Surgeons (STS) scores, it appeared that TAVI provided the most benefit to patients with lower STS scores who were less sick, but STS score did not affect mortality risk in the standard therapy group.

"The ultimate value will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVI and render the intervention futile," Dr. Makkar said.

The 358-patient PARTNER trial compared TAVI with standard therapy in high-risk patients with severe aortic stenosis at 21 centers. Patients were randomized to transfemoral implantation of a balloon-expandable bovine pericardial valve (the Edwards Sapien valve) or standard therapy (including balloon aortic valvuloplasty in 84%) between May 2007 and March 2009.

The reported results applied to a prespecified cohort of patients whom surgeons considered not to be suitable candidates for surgery (cohort B). An ongoing portion of the trial is following a separate cohort of patients with high surgical risk who nevertheless were considered to be candidates for surgery (cohort A).

Based on the results from cohort B, the Food and Drug Administration approved the Edwards Sapien valve in November for the treatment of patients with aortic stenosis who are not considered candidates for surgery.

The 2-year results also showed that rates of repeat hospitalization were lower in the TAVI group at year 2 (35%), compared with the standard therapy group (72%), Dr. Makkar reported. Patients in the TAVI group gained nearly a year of days alive outside of the hospital, compared with patients given standard therapy – 699 days vs. 355.

By year 2, only 17% of patients in the TAVI group had New York Heart Association Class III or IV symptoms, compared with 58% in the standard therapy group.

Strokes were more common in the TAVI group (14%), compared with the standard therapy group (6%) at year 2. The TAVI group had higher rates of strokes than did the standard therapy group in the first 30 days after treatment and between years 1 and 2, but not between 30 days and 1 year after treatment, he said. Excess strokes in the TAVI group in the first 30 days were driven by ischemic causes, but excess strokes between years 1 and 2 were mainly due to hemorrhagic strokes, Dr. Makkar said.

The reasons for the hemorrhagic strokes appear to be multifactorial, including severe falls in three patients in the TAVI group, potential effects of medications, and other factors.

For strokes and all-cause mortality combined, 46% in the TAVI group and 68% in the standard therapy met this end point. Five patients would need to be treated with TAVI to avoid stroke or death, compared with usual care.

In explaining the risks to patients, Dr. Makkar said he would tell them that for every four patients treated with TAVI instead of standard therapy, one patient will survive. For every 12-13 patients treated with TAVI instead of standard therapy, 1 will develop a stroke.

Or, as Dr. Samir Kapadia of the Cleveland Clinic phrased it at a press briefing, patients in this population have a 50-50 chance of being alive at 2 years if they’re treated with TAVI and a 1 in 20 chance of having a stroke.

Patients in both treatment groups had a mean age of 83 years.

The hemodynamic effects of the implanted valves appeared to be stable between years 1 and 2, with sustained mean gradients and valve areas. Among patients with paravalvular leaks, 41% in each group died.

Edwards Lifesciences, which markets the Edwards Sapien valve, funded the study and was involved in its design, data collection, and monitoring. Dr. Makkar holds stock in Entourage Technologies, has received fees for consulting, speaking, or honoraria from Abbott Vascular, Medtronic and Abiomed, and has received research funds from Edwards Lifesciences. Dr. Mack and Dr. Kapadia said they have no conflicts of interest.

SAN FRANCISCO – Platelet inhibition in response to adenosine diphosphate antagonists strongly predicted stent thrombosis within 30 days of implanting a drug-eluting stent in 8,575 patients on dual-antiplatelet therapy after percutaneous coronary intervention.

Both absolute and relative levels of platelet inhibition to ADP antagonists, as measured by the VerifyNow P2712 test, independently predicted early stent thrombosis, with a significant proportion of the thromboses associated with poor platelet response to clopidogrel, which inhibits the P2Y12 receptor, Dr. Gregg W. Stone and his associates reported.

The study assessed platelet function after dual-antiplatelet therapy loading using a suite of VerifyNow branded tests, and the findings may not be applicable to other tests. The tests assessed platelet reactivity to aspirin (VerifyNow Aspirin) and clopidogrel (VerifyNow P2Y12), and assessed overall platelet responsiveness (VerifyNow IIb/IIa).

The risk for stent thrombosis tripled in patients with P2Y12 reaction units (PRU) measuring greater than 208, which accounted for 50% of stent thromboses in a multivariable analysis, he said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The risk nearly tripled with a PRU of 230 or greater or with 11% or less inhibition of PY12, which accounted for 41% and 33% of stent thromboses, respectively.

Factors that were not predictive of 30-day risk of stent thrombosis included the baseline level of platelet P2Y12 response, platelet responsiveness to aspirin, and overall platelet responsiveness after dual-antiplatelet therapy loading, he said.

Giving agents that are more effective at inhibiting ADP-induced platelet activation to large patient populations should reduce the risk of 30-day stent thrombosis based on these findings, said Dr. Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and professor of medicine at Columbia University, New York.

In that sense, the results of the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) support the results of two previous studies, the TRITON-TIMI (Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction) 38 trial (N. Engl. J. Med. 2007;357:2001-15) and the PLATO (Platelet Inhibition and Patient Outcomes) study (N. Engl. J. Med. 2009;361:1045-57), he said.

On the other hand, the low rate of stent thrombosis – 0.46%, or only 39 in 30 days – and the modest sensitivity and specificity of platelet function testing suggest that testing platelet responsiveness to ADP antagonists probably isn’t helpful for clinical decision-making about preventing 30-day stent thrombosis in most patients, although the findings may be helpful on a population level.

Testing for a PRU greater than 208 was 74% sensitive and 57% specific, for an accuracy of 58%. Testing for a PRU of 230 or greater was 64% sensitive and 65% specific, for an accuracy of 65%. Testing for P2Y12 inhibition of 11% or less was 51% sensitive and 80% specific, for an accuracy of 80%.

Measuring platelet responsiveness to ADP antagonists was predictive in both diabetic and nondiabetic patients and in patients with acute coronary syndromes, but not in patients with stable coronary artery disease.

Thirty of the 39 stent thromboses occurred in the 4,347 patients with acute coronary syndromes. In this subgroup, a PRU greater than 208 or P2Y12 inhibition of 11% or less predicted a fourfold increased risk for 30-day stent thrombosis, and a PRU of 230 or greater predicted a tripling in risk. These tests flagged 60%, 44%, and 41% of 30-day stent thromboses, respectively, in patients with acute coronary syndromes.

In patients without acute coronary syndromes, the tests were not significantly associated with 30-day risk for stent thrombosis.

Dr. Stone suggested that the poor prognostic accuracy in patients without acute coronary syndromes and the low rate of stent thrombosis in this subgroup (only 9 of the 39 thromboses that occurred) may explain the negative results in two previous trials involving clopidogrel and platelet reactivity, the GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) study (JAMA 2011;305:1097-1105) and the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

Although ADAPT-DES was a registry, "we tried to run it more like a randomized trial," Dr. Stone said. Eleven sites in the United States and Germany enrolled patients between January 2008 and September 2011 who underwent successful and uncomplicated PCI with an approved drug-eluting stent.

The ADAPT-DES study plans a 2-year follow-up to assess associations between platelet responsiveness testing and the risk of late or very late stent thrombosis.

The study was funded by the Cardiovascular Research Foundation, Accumetrics (which makes the VerifyNow tests), Boston Scientific, Abbott Vascular, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, and Volcano. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.

SAN FRANCISCO – Platelet inhibition in response to adenosine diphosphate antagonists strongly predicted stent thrombosis within 30 days of implanting a drug-eluting stent in 8,575 patients on dual-antiplatelet therapy after percutaneous coronary intervention.

Both absolute and relative levels of platelet inhibition to ADP antagonists, as measured by the VerifyNow P2712 test, independently predicted early stent thrombosis, with a significant proportion of the thromboses associated with poor platelet response to clopidogrel, which inhibits the P2Y12 receptor, Dr. Gregg W. Stone and his associates reported.

The study assessed platelet function after dual-antiplatelet therapy loading using a suite of VerifyNow branded tests, and the findings may not be applicable to other tests. The tests assessed platelet reactivity to aspirin (VerifyNow Aspirin) and clopidogrel (VerifyNow P2Y12), and assessed overall platelet responsiveness (VerifyNow IIb/IIa).

The risk for stent thrombosis tripled in patients with P2Y12 reaction units (PRU) measuring greater than 208, which accounted for 50% of stent thromboses in a multivariable analysis, he said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The risk nearly tripled with a PRU of 230 or greater or with 11% or less inhibition of PY12, which accounted for 41% and 33% of stent thromboses, respectively.

Factors that were not predictive of 30-day risk of stent thrombosis included the baseline level of platelet P2Y12 response, platelet responsiveness to aspirin, and overall platelet responsiveness after dual-antiplatelet therapy loading, he said.

Giving agents that are more effective at inhibiting ADP-induced platelet activation to large patient populations should reduce the risk of 30-day stent thrombosis based on these findings, said Dr. Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and professor of medicine at Columbia University, New York.

In that sense, the results of the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) support the results of two previous studies, the TRITON-TIMI (Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction) 38 trial (N. Engl. J. Med. 2007;357:2001-15) and the PLATO (Platelet Inhibition and Patient Outcomes) study (N. Engl. J. Med. 2009;361:1045-57), he said.

On the other hand, the low rate of stent thrombosis – 0.46%, or only 39 in 30 days – and the modest sensitivity and specificity of platelet function testing suggest that testing platelet responsiveness to ADP antagonists probably isn’t helpful for clinical decision-making about preventing 30-day stent thrombosis in most patients, although the findings may be helpful on a population level.

Testing for a PRU greater than 208 was 74% sensitive and 57% specific, for an accuracy of 58%. Testing for a PRU of 230 or greater was 64% sensitive and 65% specific, for an accuracy of 65%. Testing for P2Y12 inhibition of 11% or less was 51% sensitive and 80% specific, for an accuracy of 80%.

Measuring platelet responsiveness to ADP antagonists was predictive in both diabetic and nondiabetic patients and in patients with acute coronary syndromes, but not in patients with stable coronary artery disease.

Thirty of the 39 stent thromboses occurred in the 4,347 patients with acute coronary syndromes. In this subgroup, a PRU greater than 208 or P2Y12 inhibition of 11% or less predicted a fourfold increased risk for 30-day stent thrombosis, and a PRU of 230 or greater predicted a tripling in risk. These tests flagged 60%, 44%, and 41% of 30-day stent thromboses, respectively, in patients with acute coronary syndromes.

In patients without acute coronary syndromes, the tests were not significantly associated with 30-day risk for stent thrombosis.

Dr. Stone suggested that the poor prognostic accuracy in patients without acute coronary syndromes and the low rate of stent thrombosis in this subgroup (only 9 of the 39 thromboses that occurred) may explain the negative results in two previous trials involving clopidogrel and platelet reactivity, the GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) study (JAMA 2011;305:1097-1105) and the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

Although ADAPT-DES was a registry, "we tried to run it more like a randomized trial," Dr. Stone said. Eleven sites in the United States and Germany enrolled patients between January 2008 and September 2011 who underwent successful and uncomplicated PCI with an approved drug-eluting stent.

The ADAPT-DES study plans a 2-year follow-up to assess associations between platelet responsiveness testing and the risk of late or very late stent thrombosis.

The study was funded by the Cardiovascular Research Foundation, Accumetrics (which makes the VerifyNow tests), Boston Scientific, Abbott Vascular, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, and Volcano. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.

SAN FRANCISCO – Platelet inhibition in response to adenosine diphosphate antagonists strongly predicted stent thrombosis within 30 days of implanting a drug-eluting stent in 8,575 patients on dual-antiplatelet therapy after percutaneous coronary intervention.

Both absolute and relative levels of platelet inhibition to ADP antagonists, as measured by the VerifyNow P2712 test, independently predicted early stent thrombosis, with a significant proportion of the thromboses associated with poor platelet response to clopidogrel, which inhibits the P2Y12 receptor, Dr. Gregg W. Stone and his associates reported.

The study assessed platelet function after dual-antiplatelet therapy loading using a suite of VerifyNow branded tests, and the findings may not be applicable to other tests. The tests assessed platelet reactivity to aspirin (VerifyNow Aspirin) and clopidogrel (VerifyNow P2Y12), and assessed overall platelet responsiveness (VerifyNow IIb/IIa).

The risk for stent thrombosis tripled in patients with P2Y12 reaction units (PRU) measuring greater than 208, which accounted for 50% of stent thromboses in a multivariable analysis, he said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The risk nearly tripled with a PRU of 230 or greater or with 11% or less inhibition of PY12, which accounted for 41% and 33% of stent thromboses, respectively.

Factors that were not predictive of 30-day risk of stent thrombosis included the baseline level of platelet P2Y12 response, platelet responsiveness to aspirin, and overall platelet responsiveness after dual-antiplatelet therapy loading, he said.

Giving agents that are more effective at inhibiting ADP-induced platelet activation to large patient populations should reduce the risk of 30-day stent thrombosis based on these findings, said Dr. Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and professor of medicine at Columbia University, New York.

In that sense, the results of the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) support the results of two previous studies, the TRITON-TIMI (Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction) 38 trial (N. Engl. J. Med. 2007;357:2001-15) and the PLATO (Platelet Inhibition and Patient Outcomes) study (N. Engl. J. Med. 2009;361:1045-57), he said.

On the other hand, the low rate of stent thrombosis – 0.46%, or only 39 in 30 days – and the modest sensitivity and specificity of platelet function testing suggest that testing platelet responsiveness to ADP antagonists probably isn’t helpful for clinical decision-making about preventing 30-day stent thrombosis in most patients, although the findings may be helpful on a population level.

Testing for a PRU greater than 208 was 74% sensitive and 57% specific, for an accuracy of 58%. Testing for a PRU of 230 or greater was 64% sensitive and 65% specific, for an accuracy of 65%. Testing for P2Y12 inhibition of 11% or less was 51% sensitive and 80% specific, for an accuracy of 80%.

Measuring platelet responsiveness to ADP antagonists was predictive in both diabetic and nondiabetic patients and in patients with acute coronary syndromes, but not in patients with stable coronary artery disease.

Thirty of the 39 stent thromboses occurred in the 4,347 patients with acute coronary syndromes. In this subgroup, a PRU greater than 208 or P2Y12 inhibition of 11% or less predicted a fourfold increased risk for 30-day stent thrombosis, and a PRU of 230 or greater predicted a tripling in risk. These tests flagged 60%, 44%, and 41% of 30-day stent thromboses, respectively, in patients with acute coronary syndromes.

In patients without acute coronary syndromes, the tests were not significantly associated with 30-day risk for stent thrombosis.

Dr. Stone suggested that the poor prognostic accuracy in patients without acute coronary syndromes and the low rate of stent thrombosis in this subgroup (only 9 of the 39 thromboses that occurred) may explain the negative results in two previous trials involving clopidogrel and platelet reactivity, the GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) study (JAMA 2011;305:1097-1105) and the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

Although ADAPT-DES was a registry, "we tried to run it more like a randomized trial," Dr. Stone said. Eleven sites in the United States and Germany enrolled patients between January 2008 and September 2011 who underwent successful and uncomplicated PCI with an approved drug-eluting stent.

The ADAPT-DES study plans a 2-year follow-up to assess associations between platelet responsiveness testing and the risk of late or very late stent thrombosis.

The study was funded by the Cardiovascular Research Foundation, Accumetrics (which makes the VerifyNow tests), Boston Scientific, Abbott Vascular, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, and Volcano. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – A majority of patients who are rehospitalized after surgery have a postoperative complication, most commonly after colectomy, lower extremity bypass, or carotid endarterectomy.

Reducing postoperative complications could reduce costs associated with readmissions by millions of dollars per year, a retrospective study of data on 90,932 patients from 214 hospitals suggests.

Investigators linked records from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and the Medicare Provider Analysis and Review files for patients aged 65 years or older who underwent surgery in 2005-2008.

Within 30 days of surgery, 13% of patients were readmitted. A postoperative complication listed in the ACS-NSQIP registry was seen in 53% of readmitted patients compared with 16% of patients who did not need readmission, Dr. Elise H. Lawson and her associates reported at the annual clinical congress of the American College of Surgeons.

The study looked at 20 postoperative complications, including surgical site infections, wound disruption, pneumonia, unplanned intubation, pulmonary embolism, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, coma, cardiac arrest requiring CPR, myocardial infarction, bleeding requiring transfusion, deep venous thrombosis, sepsis or septic shock, being on a ventilator for more than 48 hours, and an unplanned return to the OR, among others.

Colectomy was associated with the greatest number of readmissions, followed by lower extremity bypass and carotid endarterectomy. After colectomy, 27% of patients developed a complication, and 13.4% of all colectomy patients were readmitted within 30 days.

Readmission rates after colectomy were 28% for patients who developed postoperative complications and 8% for patients without complications, said Dr. Lawson of the University of California, Los Angeles. She won the College’s 2011 Excellence in Research Award for her study.

Hypothetically, if postoperative complications could be prevented after colectomy, the risk-adjusted probability of readmission within 30 days would be 8%, she said. The study adjusted for the effects of many other factors that influenced the risk of having a postoperative complication, including age, sex, body mass index, functional status, emergency procedures, smoking, renal failure, and diabetes.

Not only did patients with complications have more readmissions, but those readmissions were more expensive. The cost for readmission after colectomy was $13,400 for patients with a complication and $7,500 for those without complications.

It’s unrealistic to think that a hospital could prevent all postoperative complications, Dr. Lawson said. Reducing complications after colectomy by even 10% (to 24%) would lower the overall postcolectomy readmission rate from 13.4% to 12.8%, the investigators estimated. For the 108,820 colectomies performed each year in Medicare beneficiaries aged 65 years or older, a 10% reduction in postoperative complications would reduce costs from readmissions alone by $9.3 million per year, she said.

Reducing complications after colectomy by 30% (to 19%) would lower the postcolectomy readmission rate to 11.7% and save an estimated $28 million per year in readmission costs. Halving the postcolectomy complication rate (to 13.5%) would reduce the readmission rate to 10.6% and save an estimated $46 million per year in readmission costs.

Previous data suggest that 13% of surgical patients and 16% of medical patients are readmitted after discharge from hospitalization, accounting for an estimated $17 billion in Medicare costs. Medicare plans to reduce payments for readmissions starting in 2013.

The reasons that patients are readmitted are not well understood, which was one motivation for the study, Dr. Lawson said. Unplanned readmissions that are related to the initial surgery may be due to postoperative complications or exacerbations of a preoperative comorbidity. Unplanned readmissions also may be for reasons unrelated to the initial surgery, such as for trauma or falls. In other cases, readmission may be planned for chemotherapy or elective procedures. The study excluded patients who died before discharge or who were not discharged from the primary hospitalization.

Dr. Lawson said she has no relevant conflicts of interest.

SAN FRANCISCO – A majority of patients who are rehospitalized after surgery have a postoperative complication, most commonly after colectomy, lower extremity bypass, or carotid endarterectomy.

Reducing postoperative complications could reduce costs associated with readmissions by millions of dollars per year, a retrospective study of data on 90,932 patients from 214 hospitals suggests.

Investigators linked records from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and the Medicare Provider Analysis and Review files for patients aged 65 years or older who underwent surgery in 2005-2008.

Within 30 days of surgery, 13% of patients were readmitted. A postoperative complication listed in the ACS-NSQIP registry was seen in 53% of readmitted patients compared with 16% of patients who did not need readmission, Dr. Elise H. Lawson and her associates reported at the annual clinical congress of the American College of Surgeons.

The study looked at 20 postoperative complications, including surgical site infections, wound disruption, pneumonia, unplanned intubation, pulmonary embolism, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, coma, cardiac arrest requiring CPR, myocardial infarction, bleeding requiring transfusion, deep venous thrombosis, sepsis or septic shock, being on a ventilator for more than 48 hours, and an unplanned return to the OR, among others.

Colectomy was associated with the greatest number of readmissions, followed by lower extremity bypass and carotid endarterectomy. After colectomy, 27% of patients developed a complication, and 13.4% of all colectomy patients were readmitted within 30 days.

Readmission rates after colectomy were 28% for patients who developed postoperative complications and 8% for patients without complications, said Dr. Lawson of the University of California, Los Angeles. She won the College’s 2011 Excellence in Research Award for her study.

Hypothetically, if postoperative complications could be prevented after colectomy, the risk-adjusted probability of readmission within 30 days would be 8%, she said. The study adjusted for the effects of many other factors that influenced the risk of having a postoperative complication, including age, sex, body mass index, functional status, emergency procedures, smoking, renal failure, and diabetes.

Not only did patients with complications have more readmissions, but those readmissions were more expensive. The cost for readmission after colectomy was $13,400 for patients with a complication and $7,500 for those without complications.

It’s unrealistic to think that a hospital could prevent all postoperative complications, Dr. Lawson said. Reducing complications after colectomy by even 10% (to 24%) would lower the overall postcolectomy readmission rate from 13.4% to 12.8%, the investigators estimated. For the 108,820 colectomies performed each year in Medicare beneficiaries aged 65 years or older, a 10% reduction in postoperative complications would reduce costs from readmissions alone by $9.3 million per year, she said.

Reducing complications after colectomy by 30% (to 19%) would lower the postcolectomy readmission rate to 11.7% and save an estimated $28 million per year in readmission costs. Halving the postcolectomy complication rate (to 13.5%) would reduce the readmission rate to 10.6% and save an estimated $46 million per year in readmission costs.

Previous data suggest that 13% of surgical patients and 16% of medical patients are readmitted after discharge from hospitalization, accounting for an estimated $17 billion in Medicare costs. Medicare plans to reduce payments for readmissions starting in 2013.

The reasons that patients are readmitted are not well understood, which was one motivation for the study, Dr. Lawson said. Unplanned readmissions that are related to the initial surgery may be due to postoperative complications or exacerbations of a preoperative comorbidity. Unplanned readmissions also may be for reasons unrelated to the initial surgery, such as for trauma or falls. In other cases, readmission may be planned for chemotherapy or elective procedures. The study excluded patients who died before discharge or who were not discharged from the primary hospitalization.

Dr. Lawson said she has no relevant conflicts of interest.

SAN FRANCISCO – A majority of patients who are rehospitalized after surgery have a postoperative complication, most commonly after colectomy, lower extremity bypass, or carotid endarterectomy.

Reducing postoperative complications could reduce costs associated with readmissions by millions of dollars per year, a retrospective study of data on 90,932 patients from 214 hospitals suggests.

Investigators linked records from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and the Medicare Provider Analysis and Review files for patients aged 65 years or older who underwent surgery in 2005-2008.

Within 30 days of surgery, 13% of patients were readmitted. A postoperative complication listed in the ACS-NSQIP registry was seen in 53% of readmitted patients compared with 16% of patients who did not need readmission, Dr. Elise H. Lawson and her associates reported at the annual clinical congress of the American College of Surgeons.

The study looked at 20 postoperative complications, including surgical site infections, wound disruption, pneumonia, unplanned intubation, pulmonary embolism, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, coma, cardiac arrest requiring CPR, myocardial infarction, bleeding requiring transfusion, deep venous thrombosis, sepsis or septic shock, being on a ventilator for more than 48 hours, and an unplanned return to the OR, among others.

Colectomy was associated with the greatest number of readmissions, followed by lower extremity bypass and carotid endarterectomy. After colectomy, 27% of patients developed a complication, and 13.4% of all colectomy patients were readmitted within 30 days.

Readmission rates after colectomy were 28% for patients who developed postoperative complications and 8% for patients without complications, said Dr. Lawson of the University of California, Los Angeles. She won the College’s 2011 Excellence in Research Award for her study.

Hypothetically, if postoperative complications could be prevented after colectomy, the risk-adjusted probability of readmission within 30 days would be 8%, she said. The study adjusted for the effects of many other factors that influenced the risk of having a postoperative complication, including age, sex, body mass index, functional status, emergency procedures, smoking, renal failure, and diabetes.

Not only did patients with complications have more readmissions, but those readmissions were more expensive. The cost for readmission after colectomy was $13,400 for patients with a complication and $7,500 for those without complications.

It’s unrealistic to think that a hospital could prevent all postoperative complications, Dr. Lawson said. Reducing complications after colectomy by even 10% (to 24%) would lower the overall postcolectomy readmission rate from 13.4% to 12.8%, the investigators estimated. For the 108,820 colectomies performed each year in Medicare beneficiaries aged 65 years or older, a 10% reduction in postoperative complications would reduce costs from readmissions alone by $9.3 million per year, she said.

Reducing complications after colectomy by 30% (to 19%) would lower the postcolectomy readmission rate to 11.7% and save an estimated $28 million per year in readmission costs. Halving the postcolectomy complication rate (to 13.5%) would reduce the readmission rate to 10.6% and save an estimated $46 million per year in readmission costs.

Previous data suggest that 13% of surgical patients and 16% of medical patients are readmitted after discharge from hospitalization, accounting for an estimated $17 billion in Medicare costs. Medicare plans to reduce payments for readmissions starting in 2013.

The reasons that patients are readmitted are not well understood, which was one motivation for the study, Dr. Lawson said. Unplanned readmissions that are related to the initial surgery may be due to postoperative complications or exacerbations of a preoperative comorbidity. Unplanned readmissions also may be for reasons unrelated to the initial surgery, such as for trauma or falls. In other cases, readmission may be planned for chemotherapy or elective procedures. The study excluded patients who died before discharge or who were not discharged from the primary hospitalization.

Dr. Lawson said she has no relevant conflicts of interest.