ACC 2013

SAN FRANCISCO – Transcatheter aortic valve replacements seem to be holding up without feared increases in rates of stroke or regurgitation beyond what’s seen soon after the procedure, 3-year data from the PARTNER trial of 699 elderly, high-risk patients showed.

Rates of death from any cause were similar between patients randomized to transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) at each yearly follow-up so far. Those rates (the primary endpoint of the trial) were 24.3% in the TAVR group and 26.8% in SAVR group at 1 year, 33.7% and 34.6% at 2 years, and 442% and 44.8% at 3 years, respectively, according to ongoing follow-up of the PARTNER (Transcatheter vs. Surgical Aortic-Valve Replacement in High-Risk Patients) study.

Previously data had shown a higher stroke rate within 30 days of TAVR (5%), compared with SAVR (2%), though the difference did not reach statistical significance. By 3 years, the stroke rate in the surgery group caught up and even surpassed that in the TAVR group. After TAVR, stroke rates were 6% at 1 year, 8% at 2 years and 8% at 3 years, compared with rates of 3%, 5% and 9%, respectively, in the SAVR group, Dr. Vinod H. Thourani and his associates reported at the annual meeting of the American College of Cardiology. None of the stroke differences reached statistical significance.

Paravalvular leaks were common and more likely with TAVR at all follow-up time points. Even mild leakage after either procedure was associated with an unexpected, significantly increased risk of death, said Dr. Thourani, codirector of the Structural Heart and Valve Center and associate professor of cardiology at Emory University, Atlanta. Death rates in patients with mild aortic regurgitation of any kind (paravalvular or central) after TAVR were 26% at year 1, 32% at year 2, and 47% at year 3. For moderate to severe aortic regurgitation after TAVR, death rates increased to 38% at 1 year, 54% at 2 years, and 61% at 3 years.

The increased death risk with mild regurgitation has not shown up in European patient registries and caught investigators by surprise. The reason for this association in the study is a mystery, he said.

Echocardiographic analysis showed that hemodynamic performance after TAVR was maintained at 3 years, with similar valve areas and gradients, compared with SAVR. Both groups had significant improvements in left ventricular ejection fractions and left ventricular mass.

The PARTNER study included elderly patients with severe aortic stenosis who had a Society of Thoracic Surgeons (STS) score of at least 10%, suggesting they would be at high risk from surgery. Patients were randomized to undergo TAVR or SAVR at 1 of 25 sites in three countries and those in the TAVR group were further randomized to either transfemoral or transapical approach to placement of the balloon-expandable bovine pericardial valve, the first-generation Edwards SAPIEN transcatheter heart valve system (N. Engl. J. Med. 2011;364:2187-98).

Combining all-cause mortality or strokes, rates for TAVR and SAVR at 1 year were 27% and 29%, respectively, at 2 years were 37% and 36%, and at 3 years were 47% and 46%, respectively, he said.

Among clinical outcomes, rates of major vascular complications were significantly higher in the TAVR group, compared with SAVR: 12% vs. 4% at year 1, rates that held steady in years 2 and 3. Major bleeding was significantly less likely in the TAVR group each year, compared with SAVR: 16% vs. 27% in year 1, 19% vs. 30% in year 2, and 21% vs. 32% in year 3. Rates of endocarditis were similar between groups each year. No patients in either group developed structural valve deterioration requiring aortic valve replacement. Roughly 80% in each group had relief of symptoms.

Future efforts should aim to reduce procedure-related complications from TAVR, including strokes, vascular events, and paravalvular regurgitation, Dr. Thourani said.

"With a 44% mortality at 3 years, what we have to learn is how to select better patients," Dr. Bernard J. Gersh commented during a panel discussion of the findings. Dr. Gersh is professor of medicine at the Mayo Clinic, Rochester, Minn.

Experts in Europe have begun a series of meetings to try to define a transcatheter-specific risk score that might be a better gauge than the STS score in selecting patients for TAVR, Dr. Thourani said.

Patients in the current analysis have a minimum of 3 years of follow-up, so the findings really give a hint of 3- to 5-year results, Dr. Thourani said. "I think we can say something about the durability of these valves."

Dr. Patrick T. O’Gara cautioned against generalizing results from the PARTNER cohort, which averaged 84 years in age. "We have durability information in the octogenarian group over 3 years of time. When we think about deploying this kind of technology in younger and healthier individuals, there remain concerns about durability and about paravalvular leaks," he said at a press briefing.

Concerns about some findings, such as the 44% mortality rate at 3 years, may amount to unnecessarily "throwing darts" at the TAVR results, he suggested. "Let’s remember that we’re dealing with a group of patients who are 84 years of age on average. Our expectations for their outcomes need to be tempered by the context in which these procedures are offered," said Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

Each TAVR costs approximately $70,000-$75,000, Dr. Thourani estimated.

Edwards Lifesciences, which makes the transcatheter valve replacement systems, funded the PARTNER trial, and Dr. Thourani and some of his coinvestigators disclosed financial relationships with the company. He also disclosed relationships with St. Jude Medical, Marquet Medical, Sorin Medical, and Medtronic. Dr. O’Gara had nothing to disclose. Dr. Gersh disclosed financial relationships with St. Jude Medical and Boston Scientific.

sboschert@frontlinemedcom.com

Twitter @sherryboschert

SAN FRANCISCO – Transcatheter aortic valve replacements seem to be holding up without feared increases in rates of stroke or regurgitation beyond what’s seen soon after the procedure, 3-year data from the PARTNER trial of 699 elderly, high-risk patients showed.

Rates of death from any cause were similar between patients randomized to transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) at each yearly follow-up so far. Those rates (the primary endpoint of the trial) were 24.3% in the TAVR group and 26.8% in SAVR group at 1 year, 33.7% and 34.6% at 2 years, and 442% and 44.8% at 3 years, respectively, according to ongoing follow-up of the PARTNER (Transcatheter vs. Surgical Aortic-Valve Replacement in High-Risk Patients) study.

Previously data had shown a higher stroke rate within 30 days of TAVR (5%), compared with SAVR (2%), though the difference did not reach statistical significance. By 3 years, the stroke rate in the surgery group caught up and even surpassed that in the TAVR group. After TAVR, stroke rates were 6% at 1 year, 8% at 2 years and 8% at 3 years, compared with rates of 3%, 5% and 9%, respectively, in the SAVR group, Dr. Vinod H. Thourani and his associates reported at the annual meeting of the American College of Cardiology. None of the stroke differences reached statistical significance.

Paravalvular leaks were common and more likely with TAVR at all follow-up time points. Even mild leakage after either procedure was associated with an unexpected, significantly increased risk of death, said Dr. Thourani, codirector of the Structural Heart and Valve Center and associate professor of cardiology at Emory University, Atlanta. Death rates in patients with mild aortic regurgitation of any kind (paravalvular or central) after TAVR were 26% at year 1, 32% at year 2, and 47% at year 3. For moderate to severe aortic regurgitation after TAVR, death rates increased to 38% at 1 year, 54% at 2 years, and 61% at 3 years.

The increased death risk with mild regurgitation has not shown up in European patient registries and caught investigators by surprise. The reason for this association in the study is a mystery, he said.

Echocardiographic analysis showed that hemodynamic performance after TAVR was maintained at 3 years, with similar valve areas and gradients, compared with SAVR. Both groups had significant improvements in left ventricular ejection fractions and left ventricular mass.

The PARTNER study included elderly patients with severe aortic stenosis who had a Society of Thoracic Surgeons (STS) score of at least 10%, suggesting they would be at high risk from surgery. Patients were randomized to undergo TAVR or SAVR at 1 of 25 sites in three countries and those in the TAVR group were further randomized to either transfemoral or transapical approach to placement of the balloon-expandable bovine pericardial valve, the first-generation Edwards SAPIEN transcatheter heart valve system (N. Engl. J. Med. 2011;364:2187-98).

Combining all-cause mortality or strokes, rates for TAVR and SAVR at 1 year were 27% and 29%, respectively, at 2 years were 37% and 36%, and at 3 years were 47% and 46%, respectively, he said.

Among clinical outcomes, rates of major vascular complications were significantly higher in the TAVR group, compared with SAVR: 12% vs. 4% at year 1, rates that held steady in years 2 and 3. Major bleeding was significantly less likely in the TAVR group each year, compared with SAVR: 16% vs. 27% in year 1, 19% vs. 30% in year 2, and 21% vs. 32% in year 3. Rates of endocarditis were similar between groups each year. No patients in either group developed structural valve deterioration requiring aortic valve replacement. Roughly 80% in each group had relief of symptoms.

Future efforts should aim to reduce procedure-related complications from TAVR, including strokes, vascular events, and paravalvular regurgitation, Dr. Thourani said.

"With a 44% mortality at 3 years, what we have to learn is how to select better patients," Dr. Bernard J. Gersh commented during a panel discussion of the findings. Dr. Gersh is professor of medicine at the Mayo Clinic, Rochester, Minn.

Experts in Europe have begun a series of meetings to try to define a transcatheter-specific risk score that might be a better gauge than the STS score in selecting patients for TAVR, Dr. Thourani said.

Patients in the current analysis have a minimum of 3 years of follow-up, so the findings really give a hint of 3- to 5-year results, Dr. Thourani said. "I think we can say something about the durability of these valves."

Dr. Patrick T. O’Gara cautioned against generalizing results from the PARTNER cohort, which averaged 84 years in age. "We have durability information in the octogenarian group over 3 years of time. When we think about deploying this kind of technology in younger and healthier individuals, there remain concerns about durability and about paravalvular leaks," he said at a press briefing.

Concerns about some findings, such as the 44% mortality rate at 3 years, may amount to unnecessarily "throwing darts" at the TAVR results, he suggested. "Let’s remember that we’re dealing with a group of patients who are 84 years of age on average. Our expectations for their outcomes need to be tempered by the context in which these procedures are offered," said Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

Each TAVR costs approximately $70,000-$75,000, Dr. Thourani estimated.

Edwards Lifesciences, which makes the transcatheter valve replacement systems, funded the PARTNER trial, and Dr. Thourani and some of his coinvestigators disclosed financial relationships with the company. He also disclosed relationships with St. Jude Medical, Marquet Medical, Sorin Medical, and Medtronic. Dr. O’Gara had nothing to disclose. Dr. Gersh disclosed financial relationships with St. Jude Medical and Boston Scientific.

sboschert@frontlinemedcom.com

Twitter @sherryboschert

SAN FRANCISCO – Transcatheter aortic valve replacements seem to be holding up without feared increases in rates of stroke or regurgitation beyond what’s seen soon after the procedure, 3-year data from the PARTNER trial of 699 elderly, high-risk patients showed.

Rates of death from any cause were similar between patients randomized to transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) at each yearly follow-up so far. Those rates (the primary endpoint of the trial) were 24.3% in the TAVR group and 26.8% in SAVR group at 1 year, 33.7% and 34.6% at 2 years, and 442% and 44.8% at 3 years, respectively, according to ongoing follow-up of the PARTNER (Transcatheter vs. Surgical Aortic-Valve Replacement in High-Risk Patients) study.

Previously data had shown a higher stroke rate within 30 days of TAVR (5%), compared with SAVR (2%), though the difference did not reach statistical significance. By 3 years, the stroke rate in the surgery group caught up and even surpassed that in the TAVR group. After TAVR, stroke rates were 6% at 1 year, 8% at 2 years and 8% at 3 years, compared with rates of 3%, 5% and 9%, respectively, in the SAVR group, Dr. Vinod H. Thourani and his associates reported at the annual meeting of the American College of Cardiology. None of the stroke differences reached statistical significance.

Paravalvular leaks were common and more likely with TAVR at all follow-up time points. Even mild leakage after either procedure was associated with an unexpected, significantly increased risk of death, said Dr. Thourani, codirector of the Structural Heart and Valve Center and associate professor of cardiology at Emory University, Atlanta. Death rates in patients with mild aortic regurgitation of any kind (paravalvular or central) after TAVR were 26% at year 1, 32% at year 2, and 47% at year 3. For moderate to severe aortic regurgitation after TAVR, death rates increased to 38% at 1 year, 54% at 2 years, and 61% at 3 years.

The increased death risk with mild regurgitation has not shown up in European patient registries and caught investigators by surprise. The reason for this association in the study is a mystery, he said.

Echocardiographic analysis showed that hemodynamic performance after TAVR was maintained at 3 years, with similar valve areas and gradients, compared with SAVR. Both groups had significant improvements in left ventricular ejection fractions and left ventricular mass.

The PARTNER study included elderly patients with severe aortic stenosis who had a Society of Thoracic Surgeons (STS) score of at least 10%, suggesting they would be at high risk from surgery. Patients were randomized to undergo TAVR or SAVR at 1 of 25 sites in three countries and those in the TAVR group were further randomized to either transfemoral or transapical approach to placement of the balloon-expandable bovine pericardial valve, the first-generation Edwards SAPIEN transcatheter heart valve system (N. Engl. J. Med. 2011;364:2187-98).

Combining all-cause mortality or strokes, rates for TAVR and SAVR at 1 year were 27% and 29%, respectively, at 2 years were 37% and 36%, and at 3 years were 47% and 46%, respectively, he said.

Among clinical outcomes, rates of major vascular complications were significantly higher in the TAVR group, compared with SAVR: 12% vs. 4% at year 1, rates that held steady in years 2 and 3. Major bleeding was significantly less likely in the TAVR group each year, compared with SAVR: 16% vs. 27% in year 1, 19% vs. 30% in year 2, and 21% vs. 32% in year 3. Rates of endocarditis were similar between groups each year. No patients in either group developed structural valve deterioration requiring aortic valve replacement. Roughly 80% in each group had relief of symptoms.

Future efforts should aim to reduce procedure-related complications from TAVR, including strokes, vascular events, and paravalvular regurgitation, Dr. Thourani said.

"With a 44% mortality at 3 years, what we have to learn is how to select better patients," Dr. Bernard J. Gersh commented during a panel discussion of the findings. Dr. Gersh is professor of medicine at the Mayo Clinic, Rochester, Minn.

Experts in Europe have begun a series of meetings to try to define a transcatheter-specific risk score that might be a better gauge than the STS score in selecting patients for TAVR, Dr. Thourani said.

Patients in the current analysis have a minimum of 3 years of follow-up, so the findings really give a hint of 3- to 5-year results, Dr. Thourani said. "I think we can say something about the durability of these valves."

Dr. Patrick T. O’Gara cautioned against generalizing results from the PARTNER cohort, which averaged 84 years in age. "We have durability information in the octogenarian group over 3 years of time. When we think about deploying this kind of technology in younger and healthier individuals, there remain concerns about durability and about paravalvular leaks," he said at a press briefing.

Concerns about some findings, such as the 44% mortality rate at 3 years, may amount to unnecessarily "throwing darts" at the TAVR results, he suggested. "Let’s remember that we’re dealing with a group of patients who are 84 years of age on average. Our expectations for their outcomes need to be tempered by the context in which these procedures are offered," said Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

Each TAVR costs approximately $70,000-$75,000, Dr. Thourani estimated.

Edwards Lifesciences, which makes the transcatheter valve replacement systems, funded the PARTNER trial, and Dr. Thourani and some of his coinvestigators disclosed financial relationships with the company. He also disclosed relationships with St. Jude Medical, Marquet Medical, Sorin Medical, and Medtronic. Dr. O’Gara had nothing to disclose. Dr. Gersh disclosed financial relationships with St. Jude Medical and Boston Scientific.

sboschert@frontlinemedcom.com

Twitter @sherryboschert

SAN FRANCISCO – Heart attacks at a regional Greek hospital spiked 44% during the country’s financial crisis, with higher rates in women, older people, and the indigent or uninsured, a study has shown.

The findings, reported by Dr. Emmanouil Makaris at the annual meeting of the American College of Cardiology, highlight some of the health costs to be paid by the populace when governments, politicians, or bankers send economies into tailspins or at least stress their underpinnings. 

The retrospective study of data on 22,093 patients admitted to the cardiology department at the General Hospital of Kalamata found 1,406 incident heart attacks among the 10,870 patients admitted from 2004 through 2007, before the Greek financial crisis, and 1,508 heart attacks among the 11,223 patients admitted in 2008 through 2011, during the ongoing crisis. The relative 44% increase in the incidence of acute MI was significant, said Dr. Makaris, a consulting cardiologist at the hospital.

In women, the incidence of acute MI rose by 51% from the period before the crisis (251 acute MIs) to the crisis era (394). The incidence of acute MI in men increased by 40% from precrisis (795) to the crisis era (1,114).

The incidence of acute MI increased by 41% for patients older than 45 years (from 944 heart attacks before to 1,363 during the crisis). In comparison, the incidence increased by 30% for patients aged 45 years or younger (from 64 before to 83 during the crisis).

The indigent or uninsured faced a 76% increased incidence of acute MI (66 heart attacks before the crisis and 116 since then), while insured patients saw a 42% increased incidence (980 before and 1,392 during the crisis).

Dr. Makaris said that many doctors at the meeting have asked him to explain how the crisis contributed to heart attacks. He described one woman who could no longer afford to buy clopidogrel, and suffered an acute MI. A man who lost his job and had no means to support his family had a heart attack, presumably with stress as a contributor.

Some people are losing their homes, unable to pay huge tax increases. Greek women are more likely to be unemployed than men and more likely to be responsible for children. Families are searching through trash bins for food, and some children faint in school from hunger. At the same time, the government’s fiscal austerity measures have slashed medical staff levels and supplies when there is greater need, he said.

Greece’s crisis is much more severe than the latest U.S. recession, in which more than 8 million people lost their jobs, but the findings should add extra concern about the effects of our homegrown financial crises.

In the United States, more women now are unemployed than men, the Los Angeles Times reported.

The U.S. Government Accountability Office reported in late 2012 that workers aged 55 years and older are less likely to be laid off in our recession than are younger workers, but once unemployed, older people have a harder time getting rehired and are more likely to take a pay cut if they do find work.

A separate study showing cardiovascular harm from Argentina’s 1999-2002 financial crisis support the Greek findings, Dr. Makaris said (Thromb. J. 2005;3:22). And a more recent U.S. study showed that employment instability increased the risk of cardiovascular events (Arch. Intern. Med. 2012;172:1731-7).

At a press briefing, moderator Dr. Fred Bove suggested that the United States should heed this warning from Greece. "I think we all see ourselves as potential victims if we don’t manage our finances," said Dr. Bove of Temple University, Philadelphia.

Dr. Makaris reported having no relevant financial disclosures.

*This story was updated on March 12, 2013.

SAN FRANCISCO – Heart attacks at a regional Greek hospital spiked 44% during the country’s financial crisis, with higher rates in women, older people, and the indigent or uninsured, a study has shown.

The findings, reported by Dr. Emmanouil Makaris at the annual meeting of the American College of Cardiology, highlight some of the health costs to be paid by the populace when governments, politicians, or bankers send economies into tailspins or at least stress their underpinnings. 

The retrospective study of data on 22,093 patients admitted to the cardiology department at the General Hospital of Kalamata found 1,406 incident heart attacks among the 10,870 patients admitted from 2004 through 2007, before the Greek financial crisis, and 1,508 heart attacks among the 11,223 patients admitted in 2008 through 2011, during the ongoing crisis. The relative 44% increase in the incidence of acute MI was significant, said Dr. Makaris, a consulting cardiologist at the hospital.

In women, the incidence of acute MI rose by 51% from the period before the crisis (251 acute MIs) to the crisis era (394). The incidence of acute MI in men increased by 40% from precrisis (795) to the crisis era (1,114).

The incidence of acute MI increased by 41% for patients older than 45 years (from 944 heart attacks before to 1,363 during the crisis). In comparison, the incidence increased by 30% for patients aged 45 years or younger (from 64 before to 83 during the crisis).

The indigent or uninsured faced a 76% increased incidence of acute MI (66 heart attacks before the crisis and 116 since then), while insured patients saw a 42% increased incidence (980 before and 1,392 during the crisis).

Dr. Makaris said that many doctors at the meeting have asked him to explain how the crisis contributed to heart attacks. He described one woman who could no longer afford to buy clopidogrel, and suffered an acute MI. A man who lost his job and had no means to support his family had a heart attack, presumably with stress as a contributor.

Some people are losing their homes, unable to pay huge tax increases. Greek women are more likely to be unemployed than men and more likely to be responsible for children. Families are searching through trash bins for food, and some children faint in school from hunger. At the same time, the government’s fiscal austerity measures have slashed medical staff levels and supplies when there is greater need, he said.

Greece’s crisis is much more severe than the latest U.S. recession, in which more than 8 million people lost their jobs, but the findings should add extra concern about the effects of our homegrown financial crises.

In the United States, more women now are unemployed than men, the Los Angeles Times reported.

The U.S. Government Accountability Office reported in late 2012 that workers aged 55 years and older are less likely to be laid off in our recession than are younger workers, but once unemployed, older people have a harder time getting rehired and are more likely to take a pay cut if they do find work.

A separate study showing cardiovascular harm from Argentina’s 1999-2002 financial crisis support the Greek findings, Dr. Makaris said (Thromb. J. 2005;3:22). And a more recent U.S. study showed that employment instability increased the risk of cardiovascular events (Arch. Intern. Med. 2012;172:1731-7).

At a press briefing, moderator Dr. Fred Bove suggested that the United States should heed this warning from Greece. "I think we all see ourselves as potential victims if we don’t manage our finances," said Dr. Bove of Temple University, Philadelphia.

Dr. Makaris reported having no relevant financial disclosures.

*This story was updated on March 12, 2013.

SAN FRANCISCO – Heart attacks at a regional Greek hospital spiked 44% during the country’s financial crisis, with higher rates in women, older people, and the indigent or uninsured, a study has shown.

The findings, reported by Dr. Emmanouil Makaris at the annual meeting of the American College of Cardiology, highlight some of the health costs to be paid by the populace when governments, politicians, or bankers send economies into tailspins or at least stress their underpinnings. 

The retrospective study of data on 22,093 patients admitted to the cardiology department at the General Hospital of Kalamata found 1,406 incident heart attacks among the 10,870 patients admitted from 2004 through 2007, before the Greek financial crisis, and 1,508 heart attacks among the 11,223 patients admitted in 2008 through 2011, during the ongoing crisis. The relative 44% increase in the incidence of acute MI was significant, said Dr. Makaris, a consulting cardiologist at the hospital.

In women, the incidence of acute MI rose by 51% from the period before the crisis (251 acute MIs) to the crisis era (394). The incidence of acute MI in men increased by 40% from precrisis (795) to the crisis era (1,114).

The incidence of acute MI increased by 41% for patients older than 45 years (from 944 heart attacks before to 1,363 during the crisis). In comparison, the incidence increased by 30% for patients aged 45 years or younger (from 64 before to 83 during the crisis).

The indigent or uninsured faced a 76% increased incidence of acute MI (66 heart attacks before the crisis and 116 since then), while insured patients saw a 42% increased incidence (980 before and 1,392 during the crisis).

Dr. Makaris said that many doctors at the meeting have asked him to explain how the crisis contributed to heart attacks. He described one woman who could no longer afford to buy clopidogrel, and suffered an acute MI. A man who lost his job and had no means to support his family had a heart attack, presumably with stress as a contributor.

Some people are losing their homes, unable to pay huge tax increases. Greek women are more likely to be unemployed than men and more likely to be responsible for children. Families are searching through trash bins for food, and some children faint in school from hunger. At the same time, the government’s fiscal austerity measures have slashed medical staff levels and supplies when there is greater need, he said.

Greece’s crisis is much more severe than the latest U.S. recession, in which more than 8 million people lost their jobs, but the findings should add extra concern about the effects of our homegrown financial crises.

In the United States, more women now are unemployed than men, the Los Angeles Times reported.

The U.S. Government Accountability Office reported in late 2012 that workers aged 55 years and older are less likely to be laid off in our recession than are younger workers, but once unemployed, older people have a harder time getting rehired and are more likely to take a pay cut if they do find work.

A separate study showing cardiovascular harm from Argentina’s 1999-2002 financial crisis support the Greek findings, Dr. Makaris said (Thromb. J. 2005;3:22). And a more recent U.S. study showed that employment instability increased the risk of cardiovascular events (Arch. Intern. Med. 2012;172:1731-7).

At a press briefing, moderator Dr. Fred Bove suggested that the United States should heed this warning from Greece. "I think we all see ourselves as potential victims if we don’t manage our finances," said Dr. Bove of Temple University, Philadelphia.

Dr. Makaris reported having no relevant financial disclosures.

*This story was updated on March 12, 2013.

SAN FRANCISCO – Sildenafil was no better than placebo for improving exercise capacity or clinical status in patients with heart failure and preserved ejection fraction, based on the results of a 24-week randomized trial published online in JAMA Mar. 11 and presented simultaneously at the annual meeting of the American College of Cardiology.

Sildenafil (Viagra), a phosphodiesterase-5 inhibitor, was shown beneficial in a previous single-center study of patients with heart failure and preserved ejection fraction (HFPEF). In the randomized trial, however, sildenafil had no significant effect "on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure," wrote lead investigator Dr. Margaret Redfield, professor of medicine at the Mayo Clinic in Rochester, Minn., and her colleagues (JAMA 2013 Mar. 11 [doi:10.1001/jama.2013.2024]).

Further, sildenafil appeared to be associated with poorer outcomes as "renal function worsened more and NT-proBNP [N-terminal fragment of the precursor to brain-type natriuretic peptide], endothelin-1, and uric acid levels increased more in patients treated with sildenafil," the researchers wrote. There was a trend, though not significant, for more patients in the sildenafil group to withdraw consent, die, or be too ill to perform the cardiopulmonary exercise test.

The researchers randomized 113 HFPEF patients to 20 mg of sildenafil three times daily for 12 weeks, followed by 60 mg three times daily for 12 weeks; 103 others were randomized to placebo in the multicenter trial.

At week 24, there were no statistically significant differences between the placebo and sildenafil groups in median changes in peak oxygen consumption (P = 0.90); median clinical status rank score—a composite of quality of life changes and times to death or hospitalization (P = 0.85); or changes in 6-minute walk distance (placebo 15.0 m, sildenafil 5.0 m; P = 0.92).

The median age in the trial was 69 years, 48% of the patients were women, and patients were under treatment for diabetes, atrial fibrillation, kidney disease, and other comorbidities. They were stable at baseline with ejection fractions equal to or greater than 50%, but had reduced exercise capacity, median peak oxygen consumption, and 6-minute walk distances. Their left atrial volumes and other measurements were consistent with chronically elevated left ventricular filling pressures.

A higher incidence of vascular adverse events was seen in the sildenafil group and included headache, flushing, and hypotension. Arterial elasticity and systemic vascular resistance tended to decrease more in sildenafil patients, but there were no significant changes in mean arterial pressure between the two groups.

Cardiac, respiratory, or other serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Three people died in the sildenafil arm, but none in the placebo arm.

The "modest but statistically significant worsening of renal function" in sildenafil patients has not been reported before in studies of pulmonary arterial hypertension and erectile dysfunction, the investigators noted.

A previous single-center study found a benefit for sildenafil over placebo in HFPEF for left ventricular diastolic function, right ventricular systolic function, and left ventricular hypertrophy; the effect on exercise capacity was not tested (Circulation 2011;124:164-74).

"In that study, patients with HFPEF had fewer comorbidities and significantly higher blood pressure, left ventricular mass, and pulmonary artery systolic pressure ... [plus] catheterization-documented pulmonary arterial hypertension, profound right ventricular systolic dysfunction, and right ventricular failure. [The] profile [was] somewhat atypical for HFPEF cohorts," the investigators wrote.

"It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs’ ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HFPEF," they wrote.

"Although left ventricular hypertrophy was common in participants in this study, it was far less severe than among participants in the [previous] study. ... Conceivably, activation of PDE-5 or of cyclic guanosine monophosphate–sensitive downstream pathways in the left ventricle or other organs may occur only in heart failure associated with advanced left ventricular remodeling," they wrote.

The study was funded by the National Institutes of Health. Pfizer donated the sildenafil and matched placebo. The investigators reported commercial relationships with many companies, including Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche.

SAN FRANCISCO – Sildenafil was no better than placebo for improving exercise capacity or clinical status in patients with heart failure and preserved ejection fraction, based on the results of a 24-week randomized trial published online in JAMA Mar. 11 and presented simultaneously at the annual meeting of the American College of Cardiology.

Sildenafil (Viagra), a phosphodiesterase-5 inhibitor, was shown beneficial in a previous single-center study of patients with heart failure and preserved ejection fraction (HFPEF). In the randomized trial, however, sildenafil had no significant effect "on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure," wrote lead investigator Dr. Margaret Redfield, professor of medicine at the Mayo Clinic in Rochester, Minn., and her colleagues (JAMA 2013 Mar. 11 [doi:10.1001/jama.2013.2024]).

Further, sildenafil appeared to be associated with poorer outcomes as "renal function worsened more and NT-proBNP [N-terminal fragment of the precursor to brain-type natriuretic peptide], endothelin-1, and uric acid levels increased more in patients treated with sildenafil," the researchers wrote. There was a trend, though not significant, for more patients in the sildenafil group to withdraw consent, die, or be too ill to perform the cardiopulmonary exercise test.

The researchers randomized 113 HFPEF patients to 20 mg of sildenafil three times daily for 12 weeks, followed by 60 mg three times daily for 12 weeks; 103 others were randomized to placebo in the multicenter trial.

At week 24, there were no statistically significant differences between the placebo and sildenafil groups in median changes in peak oxygen consumption (P = 0.90); median clinical status rank score—a composite of quality of life changes and times to death or hospitalization (P = 0.85); or changes in 6-minute walk distance (placebo 15.0 m, sildenafil 5.0 m; P = 0.92).

The median age in the trial was 69 years, 48% of the patients were women, and patients were under treatment for diabetes, atrial fibrillation, kidney disease, and other comorbidities. They were stable at baseline with ejection fractions equal to or greater than 50%, but had reduced exercise capacity, median peak oxygen consumption, and 6-minute walk distances. Their left atrial volumes and other measurements were consistent with chronically elevated left ventricular filling pressures.

A higher incidence of vascular adverse events was seen in the sildenafil group and included headache, flushing, and hypotension. Arterial elasticity and systemic vascular resistance tended to decrease more in sildenafil patients, but there were no significant changes in mean arterial pressure between the two groups.

Cardiac, respiratory, or other serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Three people died in the sildenafil arm, but none in the placebo arm.

The "modest but statistically significant worsening of renal function" in sildenafil patients has not been reported before in studies of pulmonary arterial hypertension and erectile dysfunction, the investigators noted.

A previous single-center study found a benefit for sildenafil over placebo in HFPEF for left ventricular diastolic function, right ventricular systolic function, and left ventricular hypertrophy; the effect on exercise capacity was not tested (Circulation 2011;124:164-74).

"In that study, patients with HFPEF had fewer comorbidities and significantly higher blood pressure, left ventricular mass, and pulmonary artery systolic pressure ... [plus] catheterization-documented pulmonary arterial hypertension, profound right ventricular systolic dysfunction, and right ventricular failure. [The] profile [was] somewhat atypical for HFPEF cohorts," the investigators wrote.

"It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs’ ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HFPEF," they wrote.

"Although left ventricular hypertrophy was common in participants in this study, it was far less severe than among participants in the [previous] study. ... Conceivably, activation of PDE-5 or of cyclic guanosine monophosphate–sensitive downstream pathways in the left ventricle or other organs may occur only in heart failure associated with advanced left ventricular remodeling," they wrote.

The study was funded by the National Institutes of Health. Pfizer donated the sildenafil and matched placebo. The investigators reported commercial relationships with many companies, including Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche.

SAN FRANCISCO – Sildenafil was no better than placebo for improving exercise capacity or clinical status in patients with heart failure and preserved ejection fraction, based on the results of a 24-week randomized trial published online in JAMA Mar. 11 and presented simultaneously at the annual meeting of the American College of Cardiology.

Sildenafil (Viagra), a phosphodiesterase-5 inhibitor, was shown beneficial in a previous single-center study of patients with heart failure and preserved ejection fraction (HFPEF). In the randomized trial, however, sildenafil had no significant effect "on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure," wrote lead investigator Dr. Margaret Redfield, professor of medicine at the Mayo Clinic in Rochester, Minn., and her colleagues (JAMA 2013 Mar. 11 [doi:10.1001/jama.2013.2024]).

Further, sildenafil appeared to be associated with poorer outcomes as "renal function worsened more and NT-proBNP [N-terminal fragment of the precursor to brain-type natriuretic peptide], endothelin-1, and uric acid levels increased more in patients treated with sildenafil," the researchers wrote. There was a trend, though not significant, for more patients in the sildenafil group to withdraw consent, die, or be too ill to perform the cardiopulmonary exercise test.

The researchers randomized 113 HFPEF patients to 20 mg of sildenafil three times daily for 12 weeks, followed by 60 mg three times daily for 12 weeks; 103 others were randomized to placebo in the multicenter trial.

At week 24, there were no statistically significant differences between the placebo and sildenafil groups in median changes in peak oxygen consumption (P = 0.90); median clinical status rank score—a composite of quality of life changes and times to death or hospitalization (P = 0.85); or changes in 6-minute walk distance (placebo 15.0 m, sildenafil 5.0 m; P = 0.92).

The median age in the trial was 69 years, 48% of the patients were women, and patients were under treatment for diabetes, atrial fibrillation, kidney disease, and other comorbidities. They were stable at baseline with ejection fractions equal to or greater than 50%, but had reduced exercise capacity, median peak oxygen consumption, and 6-minute walk distances. Their left atrial volumes and other measurements were consistent with chronically elevated left ventricular filling pressures.

A higher incidence of vascular adverse events was seen in the sildenafil group and included headache, flushing, and hypotension. Arterial elasticity and systemic vascular resistance tended to decrease more in sildenafil patients, but there were no significant changes in mean arterial pressure between the two groups.

Cardiac, respiratory, or other serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Three people died in the sildenafil arm, but none in the placebo arm.

The "modest but statistically significant worsening of renal function" in sildenafil patients has not been reported before in studies of pulmonary arterial hypertension and erectile dysfunction, the investigators noted.

A previous single-center study found a benefit for sildenafil over placebo in HFPEF for left ventricular diastolic function, right ventricular systolic function, and left ventricular hypertrophy; the effect on exercise capacity was not tested (Circulation 2011;124:164-74).

"In that study, patients with HFPEF had fewer comorbidities and significantly higher blood pressure, left ventricular mass, and pulmonary artery systolic pressure ... [plus] catheterization-documented pulmonary arterial hypertension, profound right ventricular systolic dysfunction, and right ventricular failure. [The] profile [was] somewhat atypical for HFPEF cohorts," the investigators wrote.

"It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs’ ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HFPEF," they wrote.

"Although left ventricular hypertrophy was common in participants in this study, it was far less severe than among participants in the [previous] study. ... Conceivably, activation of PDE-5 or of cyclic guanosine monophosphate–sensitive downstream pathways in the left ventricle or other organs may occur only in heart failure associated with advanced left ventricular remodeling," they wrote.

The study was funded by the National Institutes of Health. Pfizer donated the sildenafil and matched placebo. The investigators reported commercial relationships with many companies, including Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche.

Two major studies on transfemoral aortic valve replacement technologies will be among the late-breaking clinical trials presented at the annual meeting of the American College of Cardiology March 9-11.

The results come at a key time, when surgeons are starting to consider transfemoral aortic valve replacement (TAVR) for low-risk as well as high-risk patients, said ACC.13 Cochair Dr. Mark G. Davies.

Other highlights among the late-breakers at the meeting include studies on biodegradable versus durable stents, statins to prevent kidney injury during percutaneous coronary intervention (PCI), short-acting antiplatelet therapy, new drugs that may reduce the size or long-term effects of heart attacks, ranolazine therapy to reduce angina in patients with diabetes, using digitalis in older patients with heart failure, and more.

He and a roster of other ACC officials provided these highlights:

• PARTNER trial: Two-year data from the Placement of Aortic Transcatheter Valve (PARTNER) trial already have suggested that results with TAVR were reasonably comparable to results with surgical aortic valve replacement (SAVR), though perhaps with increased risk of early stroke after TAVR. "But the one Achilles heel that everyone is worried about is that there will be more early strokes in TAVR," said Dr. Davies, a senior member at the Methodist Hospital Research Institute, Houston.

Three-year data from the PARTNER trial, to be presented at the meeting, should show whether the level of valvular regurgitation is increasing or not – important findings that will change practices, he said. "This is significant because we’re entering an era of entertaining these technologies for what’s considered normal or low-risk patients who might avoid a surgical aortic revascularization," said Dr. Davies. For hospitals, "it will be interesting to see if the cost-effectiveness is carried out to 3 years," he added.

• PARTNER II: This trial used a second-generation Edwards Sapien XT transcatheter heart valve and delivery system, which has a lower profile compared with the first-generation device.

The Food and Drug Administration required the Sapien and Edwards investigators to compare the newer version against SAVR before taking it to market, according to ACC Vice President Dr. Patrick T. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston.

"Most investigators and clinicians in this area are keen to hear the results of this trial, and I think most anticipate that a lower-profile device will be an improvement," he said.

• NEXT trial: Enthusiasm for a potential future of biodegradable stent products rides on hopes that biodegradable polymers might cause less arterial injury and stent thrombosis, "although it seems to me very difficult to beat very low rates of stent thrombosis with present-generation drug-eluting stents," Dr. O’Gara said. This large Japanese trial comparing a biodegradable stent polymer and a durable stent polymer in more than 3,000 patients is a major data source. The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent (NEXT) trial likely will contribute "very important information in this growing field," he said.

• DKCRUSH-III trial: A highly technical and impressively large study in China compared two interventional strategies in more than 400 patients with unprotected left main bifurcation lesions. Historically, interventionalists have been challenged by management of lesions at the distal end of the left main coronary artery and extending to the origins of the left anterior descending (LAD) artery and the circumflex artery, he said. "Manipulation of the left main in this particular area is fraught with complications and relatively high rates of recurrent events."

The prospective, multicenter Comparison of Double Kissing Crush Versus Culotte Stenting for Unprotected Distal Left Main Bifurcation Lesions (DKCRUSH-III) study randomized patients to intervention with stents placed in the LAD and circumflex arteries or to high-pressure balloons being placed in those arteries and inflated simultaneously.

• CHAMPION PHOENIX trial: Results of previous studies of the experimental antiplatelet drug cangrelor have been neutral or positive, but none of the studies were as large as the Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention (CHAMPION PHOENIX), which boasts nearly 11,000 patients. Preliminary results of the phase III trial suggested that this intravenously administered P2Y2-receptor inhibitor outperformed clopidogrel in patients requiring PCI in a composite endpoint of death, MI, ischemia-driven revascularization, and stent thrombosis at 48 hours.

The potential advantage of cangrelor is its very rapid onset and rapid offset of effects. "I think there is very keen expectation to hear the results of this trial as to whether or not this medication should be considered in the armamentarium at the time of PCI," Dr. O’Gara said.

• PRATO-ACS trial: The open-label Statin Contrast Induced Neuropathy Prevention (PRATO-ACS) trial randomized patients with non–ST-elevation acute coronary syndrome who are undergoing PCI to usual care or to taking a 40-mg dose of rosuvastatin at admission and then 20 mg/day for 1 month, to see if the statin will reduce acute kidney injury from the angiographic contrast medium.

"This is a very interesting look at the efficacy of a medication which, in this context, is likely to be extremely safe," Dr. O’Gara said.

Dr. Gary S. Mintz, chief medical officer at the Cardiovascular Research Foundation, New York, added, "This is an important problem. When you have a patient presenting acutely, you really don’t have much of a choice" but to send the patient to a catheterization lab, where almost invariably a stent is implanted, a procedure requiring angiographic contrast, which can induce acute renal insufficiency or worsen preexisting renal insufficiency. "Patients who develop significant renal insufficiency have an awful outcome, both acutely and long-term. If there’s any safe way, any easy, efficacious way to prevent acute renal insufficiency in this setting, this will become the standard of care."

• MASS COMM trial: The use of PCI is increasing in smaller hospitals as more of them develop non-open coronary artery based practices, and there’s controversy over whether these practices should have the backup of on-site cardiac surgery services, Dr. Davies said. The PCI Outcomes in Community Versus Tertiary Settings (MASS COMM) trial randomized nearly 4,000 Massachusetts residents undergoing elective PCI to one of 10 hospitals without on-site surgical backup or one of 7 hospitals with on-site backup.

• REMINDER trial: Despite all the advances in treating acute MI, a subgroup of patients still suffer enough heart damage that they go on to develop heart failure. The large, multicenter Impact of Eplerenone on Cardiovascular in Patients Post Myocardial Infarction (REMINDER) trial randomized more than 1,000 patients who’d had heart attacks within 24 hours to treatment with placebo or the aldosterone-blocker eplerenone. Outcomes to be reported include some clinical signs of worsening heart function, clinical signs that predict heart failure, and some biomarkers of worsening cardiac function.

• Select ACS trial: This multicenter, randomized, double-blind, placebo-controlled study looks at whether or not giving the investigational drug inclacumab to patients with non–ST-elevation MI who are undergoing PCI reduces short-term markers of infarct size. Inclacumab is a fully human antibody targeting P-selectin, a molecule that plays a role in sending white blood cells to the site of injury during inflammation.

"If, in fact, this agent reduces the size of the heart attack in this subgroup of patients, it potentially could have benefits long term," said ACC.13 Chairman Dr. Miguel A. Quiñones, chair of the department of cardiology in the Methodist Hospital System, Houston, and professor of medicine at Weill Cornell Medical College, New York.

• ASTRONAUT trial: Can add-on therapy with the potent direct renin inhibitor aliskiren improve outcomes in patients presenting with acute heart failure? Results of a trial in roughly 1,600 patients – the Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients with Acute Decompensated Heart Failure (ASTRONAUT) trial – may tell us.

• TERISA trial: The Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina (TERISA) trial looked at whether the drug reduced the weekly average frequency of angina in patients with diabetes, coronary artery disease, and chronic stable angina. Revascularization procedures can be challenging in diabetics, who often have small vessels, so a helpful medical therapy would be a boon, said ACC.13 Cochair Dr. Christie M. Ballantyne, director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, Houston.

• DIG trial: An analysis of data from the Digitalis Investigation Group (DIG) trial will report whether giving the inexpensive drug digoxin to patients aged 65 years or older who have heart failure reduced hospitalizations and mortality.

• STOP-HF trial: The St. Vincent’s Screening To Prevent Heart Failure (STOP-HF) study took a "very creative approach" to try and reduce the impact of the current epidemic of heart failure by catching patients before they develop symptoms, Dr. Ballantyne said. They screened people over age 40 who had risk factors for heart failure using a blood test for natriuretic peptide; those with high levels of the peptide were sent for echocardiography and were comanaged by their primary care physician with recommendations from a specialty cardiology service. The control group of patients with risk factors for heart failure received usual care without the blood test screening or collaborative management. Results will compare the prevalence and severity of left ventricular dysfunction over 5 years in the two groups.

A list of these and other late-breaking presentations can be found on the ACC.13 website.

Dr. Quinones and Dr. Davies reported having no financial disclosures. Dr. Ballantyne reported receiving speaker and consulting fees and research funds from many pharmaceutical companies. Dr. Mintz has received fees for consulting or speaking from Boston Scientific, Volcano, Medtronic, LightLab, and Pfizer. Dr. O’Gara has been on the Data and Safety Monitoring Board of Lantheus Medical Imaging.

s.boschert@elsevier.com

On Twitter @sherryboschert

Two major studies on transfemoral aortic valve replacement technologies will be among the late-breaking clinical trials presented at the annual meeting of the American College of Cardiology March 9-11.

The results come at a key time, when surgeons are starting to consider transfemoral aortic valve replacement (TAVR) for low-risk as well as high-risk patients, said ACC.13 Cochair Dr. Mark G. Davies.

Other highlights among the late-breakers at the meeting include studies on biodegradable versus durable stents, statins to prevent kidney injury during percutaneous coronary intervention (PCI), short-acting antiplatelet therapy, new drugs that may reduce the size or long-term effects of heart attacks, ranolazine therapy to reduce angina in patients with diabetes, using digitalis in older patients with heart failure, and more.

He and a roster of other ACC officials provided these highlights:

• PARTNER trial: Two-year data from the Placement of Aortic Transcatheter Valve (PARTNER) trial already have suggested that results with TAVR were reasonably comparable to results with surgical aortic valve replacement (SAVR), though perhaps with increased risk of early stroke after TAVR. "But the one Achilles heel that everyone is worried about is that there will be more early strokes in TAVR," said Dr. Davies, a senior member at the Methodist Hospital Research Institute, Houston.

Three-year data from the PARTNER trial, to be presented at the meeting, should show whether the level of valvular regurgitation is increasing or not – important findings that will change practices, he said. "This is significant because we’re entering an era of entertaining these technologies for what’s considered normal or low-risk patients who might avoid a surgical aortic revascularization," said Dr. Davies. For hospitals, "it will be interesting to see if the cost-effectiveness is carried out to 3 years," he added.

• PARTNER II: This trial used a second-generation Edwards Sapien XT transcatheter heart valve and delivery system, which has a lower profile compared with the first-generation device.

The Food and Drug Administration required the Sapien and Edwards investigators to compare the newer version against SAVR before taking it to market, according to ACC Vice President Dr. Patrick T. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston.

"Most investigators and clinicians in this area are keen to hear the results of this trial, and I think most anticipate that a lower-profile device will be an improvement," he said.

• NEXT trial: Enthusiasm for a potential future of biodegradable stent products rides on hopes that biodegradable polymers might cause less arterial injury and stent thrombosis, "although it seems to me very difficult to beat very low rates of stent thrombosis with present-generation drug-eluting stents," Dr. O’Gara said. This large Japanese trial comparing a biodegradable stent polymer and a durable stent polymer in more than 3,000 patients is a major data source. The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent (NEXT) trial likely will contribute "very important information in this growing field," he said.

• DKCRUSH-III trial: A highly technical and impressively large study in China compared two interventional strategies in more than 400 patients with unprotected left main bifurcation lesions. Historically, interventionalists have been challenged by management of lesions at the distal end of the left main coronary artery and extending to the origins of the left anterior descending (LAD) artery and the circumflex artery, he said. "Manipulation of the left main in this particular area is fraught with complications and relatively high rates of recurrent events."

The prospective, multicenter Comparison of Double Kissing Crush Versus Culotte Stenting for Unprotected Distal Left Main Bifurcation Lesions (DKCRUSH-III) study randomized patients to intervention with stents placed in the LAD and circumflex arteries or to high-pressure balloons being placed in those arteries and inflated simultaneously.

• CHAMPION PHOENIX trial: Results of previous studies of the experimental antiplatelet drug cangrelor have been neutral or positive, but none of the studies were as large as the Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention (CHAMPION PHOENIX), which boasts nearly 11,000 patients. Preliminary results of the phase III trial suggested that this intravenously administered P2Y2-receptor inhibitor outperformed clopidogrel in patients requiring PCI in a composite endpoint of death, MI, ischemia-driven revascularization, and stent thrombosis at 48 hours.

The potential advantage of cangrelor is its very rapid onset and rapid offset of effects. "I think there is very keen expectation to hear the results of this trial as to whether or not this medication should be considered in the armamentarium at the time of PCI," Dr. O’Gara said.

• PRATO-ACS trial: The open-label Statin Contrast Induced Neuropathy Prevention (PRATO-ACS) trial randomized patients with non–ST-elevation acute coronary syndrome who are undergoing PCI to usual care or to taking a 40-mg dose of rosuvastatin at admission and then 20 mg/day for 1 month, to see if the statin will reduce acute kidney injury from the angiographic contrast medium.

"This is a very interesting look at the efficacy of a medication which, in this context, is likely to be extremely safe," Dr. O’Gara said.

Dr. Gary S. Mintz, chief medical officer at the Cardiovascular Research Foundation, New York, added, "This is an important problem. When you have a patient presenting acutely, you really don’t have much of a choice" but to send the patient to a catheterization lab, where almost invariably a stent is implanted, a procedure requiring angiographic contrast, which can induce acute renal insufficiency or worsen preexisting renal insufficiency. "Patients who develop significant renal insufficiency have an awful outcome, both acutely and long-term. If there’s any safe way, any easy, efficacious way to prevent acute renal insufficiency in this setting, this will become the standard of care."

• MASS COMM trial: The use of PCI is increasing in smaller hospitals as more of them develop non-open coronary artery based practices, and there’s controversy over whether these practices should have the backup of on-site cardiac surgery services, Dr. Davies said. The PCI Outcomes in Community Versus Tertiary Settings (MASS COMM) trial randomized nearly 4,000 Massachusetts residents undergoing elective PCI to one of 10 hospitals without on-site surgical backup or one of 7 hospitals with on-site backup.

• REMINDER trial: Despite all the advances in treating acute MI, a subgroup of patients still suffer enough heart damage that they go on to develop heart failure. The large, multicenter Impact of Eplerenone on Cardiovascular in Patients Post Myocardial Infarction (REMINDER) trial randomized more than 1,000 patients who’d had heart attacks within 24 hours to treatment with placebo or the aldosterone-blocker eplerenone. Outcomes to be reported include some clinical signs of worsening heart function, clinical signs that predict heart failure, and some biomarkers of worsening cardiac function.

• Select ACS trial: This multicenter, randomized, double-blind, placebo-controlled study looks at whether or not giving the investigational drug inclacumab to patients with non–ST-elevation MI who are undergoing PCI reduces short-term markers of infarct size. Inclacumab is a fully human antibody targeting P-selectin, a molecule that plays a role in sending white blood cells to the site of injury during inflammation.

"If, in fact, this agent reduces the size of the heart attack in this subgroup of patients, it potentially could have benefits long term," said ACC.13 Chairman Dr. Miguel A. Quiñones, chair of the department of cardiology in the Methodist Hospital System, Houston, and professor of medicine at Weill Cornell Medical College, New York.

• ASTRONAUT trial: Can add-on therapy with the potent direct renin inhibitor aliskiren improve outcomes in patients presenting with acute heart failure? Results of a trial in roughly 1,600 patients – the Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients with Acute Decompensated Heart Failure (ASTRONAUT) trial – may tell us.

• TERISA trial: The Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina (TERISA) trial looked at whether the drug reduced the weekly average frequency of angina in patients with diabetes, coronary artery disease, and chronic stable angina. Revascularization procedures can be challenging in diabetics, who often have small vessels, so a helpful medical therapy would be a boon, said ACC.13 Cochair Dr. Christie M. Ballantyne, director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, Houston.

• DIG trial: An analysis of data from the Digitalis Investigation Group (DIG) trial will report whether giving the inexpensive drug digoxin to patients aged 65 years or older who have heart failure reduced hospitalizations and mortality.

• STOP-HF trial: The St. Vincent’s Screening To Prevent Heart Failure (STOP-HF) study took a "very creative approach" to try and reduce the impact of the current epidemic of heart failure by catching patients before they develop symptoms, Dr. Ballantyne said. They screened people over age 40 who had risk factors for heart failure using a blood test for natriuretic peptide; those with high levels of the peptide were sent for echocardiography and were comanaged by their primary care physician with recommendations from a specialty cardiology service. The control group of patients with risk factors for heart failure received usual care without the blood test screening or collaborative management. Results will compare the prevalence and severity of left ventricular dysfunction over 5 years in the two groups.

A list of these and other late-breaking presentations can be found on the ACC.13 website.

Dr. Quinones and Dr. Davies reported having no financial disclosures. Dr. Ballantyne reported receiving speaker and consulting fees and research funds from many pharmaceutical companies. Dr. Mintz has received fees for consulting or speaking from Boston Scientific, Volcano, Medtronic, LightLab, and Pfizer. Dr. O’Gara has been on the Data and Safety Monitoring Board of Lantheus Medical Imaging.

s.boschert@elsevier.com

On Twitter @sherryboschert

Two major studies on transfemoral aortic valve replacement technologies will be among the late-breaking clinical trials presented at the annual meeting of the American College of Cardiology March 9-11.

The results come at a key time, when surgeons are starting to consider transfemoral aortic valve replacement (TAVR) for low-risk as well as high-risk patients, said ACC.13 Cochair Dr. Mark G. Davies.

Other highlights among the late-breakers at the meeting include studies on biodegradable versus durable stents, statins to prevent kidney injury during percutaneous coronary intervention (PCI), short-acting antiplatelet therapy, new drugs that may reduce the size or long-term effects of heart attacks, ranolazine therapy to reduce angina in patients with diabetes, using digitalis in older patients with heart failure, and more.

He and a roster of other ACC officials provided these highlights:

• PARTNER trial: Two-year data from the Placement of Aortic Transcatheter Valve (PARTNER) trial already have suggested that results with TAVR were reasonably comparable to results with surgical aortic valve replacement (SAVR), though perhaps with increased risk of early stroke after TAVR. "But the one Achilles heel that everyone is worried about is that there will be more early strokes in TAVR," said Dr. Davies, a senior member at the Methodist Hospital Research Institute, Houston.

Three-year data from the PARTNER trial, to be presented at the meeting, should show whether the level of valvular regurgitation is increasing or not – important findings that will change practices, he said. "This is significant because we’re entering an era of entertaining these technologies for what’s considered normal or low-risk patients who might avoid a surgical aortic revascularization," said Dr. Davies. For hospitals, "it will be interesting to see if the cost-effectiveness is carried out to 3 years," he added.

• PARTNER II: This trial used a second-generation Edwards Sapien XT transcatheter heart valve and delivery system, which has a lower profile compared with the first-generation device.

The Food and Drug Administration required the Sapien and Edwards investigators to compare the newer version against SAVR before taking it to market, according to ACC Vice President Dr. Patrick T. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston.

"Most investigators and clinicians in this area are keen to hear the results of this trial, and I think most anticipate that a lower-profile device will be an improvement," he said.

• NEXT trial: Enthusiasm for a potential future of biodegradable stent products rides on hopes that biodegradable polymers might cause less arterial injury and stent thrombosis, "although it seems to me very difficult to beat very low rates of stent thrombosis with present-generation drug-eluting stents," Dr. O’Gara said. This large Japanese trial comparing a biodegradable stent polymer and a durable stent polymer in more than 3,000 patients is a major data source. The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent (NEXT) trial likely will contribute "very important information in this growing field," he said.

• DKCRUSH-III trial: A highly technical and impressively large study in China compared two interventional strategies in more than 400 patients with unprotected left main bifurcation lesions. Historically, interventionalists have been challenged by management of lesions at the distal end of the left main coronary artery and extending to the origins of the left anterior descending (LAD) artery and the circumflex artery, he said. "Manipulation of the left main in this particular area is fraught with complications and relatively high rates of recurrent events."

The prospective, multicenter Comparison of Double Kissing Crush Versus Culotte Stenting for Unprotected Distal Left Main Bifurcation Lesions (DKCRUSH-III) study randomized patients to intervention with stents placed in the LAD and circumflex arteries or to high-pressure balloons being placed in those arteries and inflated simultaneously.

• CHAMPION PHOENIX trial: Results of previous studies of the experimental antiplatelet drug cangrelor have been neutral or positive, but none of the studies were as large as the Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention (CHAMPION PHOENIX), which boasts nearly 11,000 patients. Preliminary results of the phase III trial suggested that this intravenously administered P2Y2-receptor inhibitor outperformed clopidogrel in patients requiring PCI in a composite endpoint of death, MI, ischemia-driven revascularization, and stent thrombosis at 48 hours.

The potential advantage of cangrelor is its very rapid onset and rapid offset of effects. "I think there is very keen expectation to hear the results of this trial as to whether or not this medication should be considered in the armamentarium at the time of PCI," Dr. O’Gara said.

• PRATO-ACS trial: The open-label Statin Contrast Induced Neuropathy Prevention (PRATO-ACS) trial randomized patients with non–ST-elevation acute coronary syndrome who are undergoing PCI to usual care or to taking a 40-mg dose of rosuvastatin at admission and then 20 mg/day for 1 month, to see if the statin will reduce acute kidney injury from the angiographic contrast medium.

"This is a very interesting look at the efficacy of a medication which, in this context, is likely to be extremely safe," Dr. O’Gara said.

Dr. Gary S. Mintz, chief medical officer at the Cardiovascular Research Foundation, New York, added, "This is an important problem. When you have a patient presenting acutely, you really don’t have much of a choice" but to send the patient to a catheterization lab, where almost invariably a stent is implanted, a procedure requiring angiographic contrast, which can induce acute renal insufficiency or worsen preexisting renal insufficiency. "Patients who develop significant renal insufficiency have an awful outcome, both acutely and long-term. If there’s any safe way, any easy, efficacious way to prevent acute renal insufficiency in this setting, this will become the standard of care."

• MASS COMM trial: The use of PCI is increasing in smaller hospitals as more of them develop non-open coronary artery based practices, and there’s controversy over whether these practices should have the backup of on-site cardiac surgery services, Dr. Davies said. The PCI Outcomes in Community Versus Tertiary Settings (MASS COMM) trial randomized nearly 4,000 Massachusetts residents undergoing elective PCI to one of 10 hospitals without on-site surgical backup or one of 7 hospitals with on-site backup.

• REMINDER trial: Despite all the advances in treating acute MI, a subgroup of patients still suffer enough heart damage that they go on to develop heart failure. The large, multicenter Impact of Eplerenone on Cardiovascular in Patients Post Myocardial Infarction (REMINDER) trial randomized more than 1,000 patients who’d had heart attacks within 24 hours to treatment with placebo or the aldosterone-blocker eplerenone. Outcomes to be reported include some clinical signs of worsening heart function, clinical signs that predict heart failure, and some biomarkers of worsening cardiac function.

• Select ACS trial: This multicenter, randomized, double-blind, placebo-controlled study looks at whether or not giving the investigational drug inclacumab to patients with non–ST-elevation MI who are undergoing PCI reduces short-term markers of infarct size. Inclacumab is a fully human antibody targeting P-selectin, a molecule that plays a role in sending white blood cells to the site of injury during inflammation.

"If, in fact, this agent reduces the size of the heart attack in this subgroup of patients, it potentially could have benefits long term," said ACC.13 Chairman Dr. Miguel A. Quiñones, chair of the department of cardiology in the Methodist Hospital System, Houston, and professor of medicine at Weill Cornell Medical College, New York.

• ASTRONAUT trial: Can add-on therapy with the potent direct renin inhibitor aliskiren improve outcomes in patients presenting with acute heart failure? Results of a trial in roughly 1,600 patients – the Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients with Acute Decompensated Heart Failure (ASTRONAUT) trial – may tell us.

• TERISA trial: The Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina (TERISA) trial looked at whether the drug reduced the weekly average frequency of angina in patients with diabetes, coronary artery disease, and chronic stable angina. Revascularization procedures can be challenging in diabetics, who often have small vessels, so a helpful medical therapy would be a boon, said ACC.13 Cochair Dr. Christie M. Ballantyne, director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, Houston.

• DIG trial: An analysis of data from the Digitalis Investigation Group (DIG) trial will report whether giving the inexpensive drug digoxin to patients aged 65 years or older who have heart failure reduced hospitalizations and mortality.

• STOP-HF trial: The St. Vincent’s Screening To Prevent Heart Failure (STOP-HF) study took a "very creative approach" to try and reduce the impact of the current epidemic of heart failure by catching patients before they develop symptoms, Dr. Ballantyne said. They screened people over age 40 who had risk factors for heart failure using a blood test for natriuretic peptide; those with high levels of the peptide were sent for echocardiography and were comanaged by their primary care physician with recommendations from a specialty cardiology service. The control group of patients with risk factors for heart failure received usual care without the blood test screening or collaborative management. Results will compare the prevalence and severity of left ventricular dysfunction over 5 years in the two groups.

A list of these and other late-breaking presentations can be found on the ACC.13 website.

Dr. Quinones and Dr. Davies reported having no financial disclosures. Dr. Ballantyne reported receiving speaker and consulting fees and research funds from many pharmaceutical companies. Dr. Mintz has received fees for consulting or speaking from Boston Scientific, Volcano, Medtronic, LightLab, and Pfizer. Dr. O’Gara has been on the Data and Safety Monitoring Board of Lantheus Medical Imaging.

s.boschert@elsevier.com

On Twitter @sherryboschert

Several studies to be presented at the annual meeting of the American College of Cardiology March 9-11 could change clinical practices. And then there are the mummies.

That’s right, mummies. More than 100 of them. They won’t be lumbering along the hallways of San Francisco’s Moscone Center, but they could tell us whether human ancestors in different parts of the world had atherosclerosis when they died and got mummified.

Following CT scans that showed atherosclerosis was common in a previous study of 52 Egyptian mummies (JACC Cardiovasc. Imaging 2011;4:315-27), investigators have imaged more than 100 mummies of people who lived 3,800 years ago in different cultures around the world. The findings should advance understanding of atherosclerosis in human civilization, ACC.13 Chairman Dr. Miguel A. Quiñones said in a teleconference preview for the press.

Some practice-changing news could come from some of the 22 late-breaking clinical trials and 2,130 abstracts accepted for presentation at the meeting, starting with highly anticipated results from a study of an intervention for atrial fibrillation, said Dr. Quiñones, chair of the department of cardiology in the Methodist Hospital System, Houston, and professor of medicine at Weill Cornell Medical College, New York.

He and a roster of other ACC officials provided these highlights:

• PREVAIL trial: Some of the most anticipated results will come from a trial of elderly patients with atrial fibrillation who were randomized to treatment with a device that allows an electrophysiologist to seal the left atrial appendage (LAA) or to conventional treatment with warfarin to reduce the risk of clots and stroke. For the nearly 1 in 10 U.S. residents aged in their 80s and 90s with atrial fibrillation, a frail physical status puts them at risk of falling, which can cause problematic bleeding if they’re being treated with anticoagulants.

Dr. Quiñones said that he expects the results of the PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients with Atrial Fibrillation Versus Long-term Warfarin Therapy) trial to be "extremely powerful in knowing whether this type of therapy is warranted in a selected group of patients with atrial fibrillation."

• RELAX trial: Treatment for heart failure in patients with a normal ejection fraction hasn’t advanced significantly in 10-15 years, but the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial could change that, he said. Roughly half of patients with heart failure have a normal ejection fraction, which is increasingly common. The trial studied whether the phosphodiesterase inhibitor sildenafil (Viagra) can improve the relaxation functions of the heart and improve clinical outcomes in these patients who have preserved pumping action but fibroses and stiffness in the heart that produce the symptoms of heart failure.

"Will this new class of agents be a breakthrough in the treatment of a disease that is very important for public health, the cost of health care, and management of diseases?" he asked.

• TACT trial: Preliminary results of TACT (Randomized Comparison of High-dose Oral Vitamins vs. Placebo in the Trial to Assess Chelation Therapy), reported at the annual meeting of the American Heart Association last fall, suggested that chelation therapy for atherosclerosis might be beneficial. Investigators will report results of treatment with chelation, high-dose oral vitamins, or placebo, alone or in combination with each other. The results "could be a game changer," Dr. Quiñones said.

• HPS2-THRIVE trial: This study of whether adding niacin and laropiprant to statins is better than statins alone in preventing future myocardial infarction in patients with previous MI or heart disease failed to reach its primary endpoint, Merck announced in late 2012. But the data on more than 25,000 patients provides enough power for potentially useful subgroup analyses, ACC.13 cochair Dr. Christie M. Ballantyne said. The cohort as a whole had low LDL levels at the start of HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events, but U.S. adults tend to have high LDL levels. Subgroup analyses may or may not show a beneficial effect of niacin/laropiprant in some populations, though it will be impossible to say whether any effect is due to the niacin or to laropiprant, which is given to reduce the side effect of flushing caused by niacin, said Dr. Ballantyne, director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, Houston.

• PEITHO trial: Results of the PEITHO (Pulmonary Embolism Thrombolysis) study are of particular interest after tennis star Venus Williams had to drop off the competitive circuit due to pulmonary embolus. The study randomized about 1,000 patients with acute pulmonary embolism in 13 countries to anticoagulation treatment with heparin alone or to heparin plus the clot-busting agent tenecteplase. "The results will help guide therapy and probably will influence the next set of chest guidelines," said ACC.13 cochair Dr. Mark G. Davies, a senior member at the Methodist Hospital Research Institute, Houston.

• Off-pump CABG: A Monday morning session combines three late-breaking trials comparing off-pump and on-pump coronary artery bypass grafting (CABG) that "probably will lead to a very spirited discussion," Dr. Davies said. One of them – the PRAGUE-6 (Off-Pump Versus On-Pump Coronary Artery Bypass Graft Surgery in High-Risk Patients) trial – could be one of the most significant presentations at the meeting, he suggested. Elderly patients were the focus of the GOPCABE (German Off Pump Coronary Artery Bypass Grafting in Elderly Patients) study. In addition, 1-year results will be presented from the CORONARY (Coronary Artery Bypass Grafting Surgery Off or On Pump Revascularization) study.

• STREAM trial: Guidelines recommend that patients with acute ST-elevation MI who present to a facility that does not perform percutaneous coronary intervention be transferred to a PCI-capable facility if the procedure can be performed within 2 hours of first medical contact. But rural residents don’t live within a stone’s throw of a catheterization lab, and even urban traffic congestion can block this strategy. The multinational STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial compared this routine-transfer strategy with routine administration of a potent bolus dose of a fibrinolytic agent if PCI cannot be performed within 1 hour, instead of the usual 2-hour window.

"This gets to the question of whether we have embedded an unnecessary and potentially dangerous time delay in a patient’s total ischemic period by stipulating that all patients should be transferred routinely for primary PCI, and whether we’re not taking advantage of this 1-hour window of opportunity, said ACC Vice President Patrick T. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston. The field of STEMI has not seen a trial of this type for many years, he said.

A list of these and other late-breaking clinical trial presentations can be found on the ACC.13 website.

Dr. Quiñones and Dr. Davies reported having no financial disclosures. Dr. Ballantyne reported receiving speaker and consulting fees and research funds from many pharmaceutical companies. Dr. O’Gara has been on the data and safety monitoring board of Lantheus Medical Imaging.

s.boschert@elsevier.com

On Twitter @sherryboschert

Several studies to be presented at the annual meeting of the American College of Cardiology March 9-11 could change clinical practices. And then there are the mummies.

That’s right, mummies. More than 100 of them. They won’t be lumbering along the hallways of San Francisco’s Moscone Center, but they could tell us whether human ancestors in different parts of the world had atherosclerosis when they died and got mummified.

Following CT scans that showed atherosclerosis was common in a previous study of 52 Egyptian mummies (JACC Cardiovasc. Imaging 2011;4:315-27), investigators have imaged more than 100 mummies of people who lived 3,800 years ago in different cultures around the world. The findings should advance understanding of atherosclerosis in human civilization, ACC.13 Chairman Dr. Miguel A. Quiñones said in a teleconference preview for the press.

Some practice-changing news could come from some of the 22 late-breaking clinical trials and 2,130 abstracts accepted for presentation at the meeting, starting with highly anticipated results from a study of an intervention for atrial fibrillation, said Dr. Quiñones, chair of the department of cardiology in the Methodist Hospital System, Houston, and professor of medicine at Weill Cornell Medical College, New York.

He and a roster of other ACC officials provided these highlights:

• PREVAIL trial: Some of the most anticipated results will come from a trial of elderly patients with atrial fibrillation who were randomized to treatment with a device that allows an electrophysiologist to seal the left atrial appendage (LAA) or to conventional treatment with warfarin to reduce the risk of clots and stroke. For the nearly 1 in 10 U.S. residents aged in their 80s and 90s with atrial fibrillation, a frail physical status puts them at risk of falling, which can cause problematic bleeding if they’re being treated with anticoagulants.

Dr. Quiñones said that he expects the results of the PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients with Atrial Fibrillation Versus Long-term Warfarin Therapy) trial to be "extremely powerful in knowing whether this type of therapy is warranted in a selected group of patients with atrial fibrillation."

• RELAX trial: Treatment for heart failure in patients with a normal ejection fraction hasn’t advanced significantly in 10-15 years, but the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial could change that, he said. Roughly half of patients with heart failure have a normal ejection fraction, which is increasingly common. The trial studied whether the phosphodiesterase inhibitor sildenafil (Viagra) can improve the relaxation functions of the heart and improve clinical outcomes in these patients who have preserved pumping action but fibroses and stiffness in the heart that produce the symptoms of heart failure.

"Will this new class of agents be a breakthrough in the treatment of a disease that is very important for public health, the cost of health care, and management of diseases?" he asked.

• TACT trial: Preliminary results of TACT (Randomized Comparison of High-dose Oral Vitamins vs. Placebo in the Trial to Assess Chelation Therapy), reported at the annual meeting of the American Heart Association last fall, suggested that chelation therapy for atherosclerosis might be beneficial. Investigators will report results of treatment with chelation, high-dose oral vitamins, or placebo, alone or in combination with each other. The results "could be a game changer," Dr. Quiñones said.

• HPS2-THRIVE trial: This study of whether adding niacin and laropiprant to statins is better than statins alone in preventing future myocardial infarction in patients with previous MI or heart disease failed to reach its primary endpoint, Merck announced in late 2012. But the data on more than 25,000 patients provides enough power for potentially useful subgroup analyses, ACC.13 cochair Dr. Christie M. Ballantyne said. The cohort as a whole had low LDL levels at the start of HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events, but U.S. adults tend to have high LDL levels. Subgroup analyses may or may not show a beneficial effect of niacin/laropiprant in some populations, though it will be impossible to say whether any effect is due to the niacin or to laropiprant, which is given to reduce the side effect of flushing caused by niacin, said Dr. Ballantyne, director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, Houston.

• PEITHO trial: Results of the PEITHO (Pulmonary Embolism Thrombolysis) study are of particular interest after tennis star Venus Williams had to drop off the competitive circuit due to pulmonary embolus. The study randomized about 1,000 patients with acute pulmonary embolism in 13 countries to anticoagulation treatment with heparin alone or to heparin plus the clot-busting agent tenecteplase. "The results will help guide therapy and probably will influence the next set of chest guidelines," said ACC.13 cochair Dr. Mark G. Davies, a senior member at the Methodist Hospital Research Institute, Houston.

• Off-pump CABG: A Monday morning session combines three late-breaking trials comparing off-pump and on-pump coronary artery bypass grafting (CABG) that "probably will lead to a very spirited discussion," Dr. Davies said. One of them – the PRAGUE-6 (Off-Pump Versus On-Pump Coronary Artery Bypass Graft Surgery in High-Risk Patients) trial – could be one of the most significant presentations at the meeting, he suggested. Elderly patients were the focus of the GOPCABE (German Off Pump Coronary Artery Bypass Grafting in Elderly Patients) study. In addition, 1-year results will be presented from the CORONARY (Coronary Artery Bypass Grafting Surgery Off or On Pump Revascularization) study.

• STREAM trial: Guidelines recommend that patients with acute ST-elevation MI who present to a facility that does not perform percutaneous coronary intervention be transferred to a PCI-capable facility if the procedure can be performed within 2 hours of first medical contact. But rural residents don’t live within a stone’s throw of a catheterization lab, and even urban traffic congestion can block this strategy. The multinational STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial compared this routine-transfer strategy with routine administration of a potent bolus dose of a fibrinolytic agent if PCI cannot be performed within 1 hour, instead of the usual 2-hour window.

"This gets to the question of whether we have embedded an unnecessary and potentially dangerous time delay in a patient’s total ischemic period by stipulating that all patients should be transferred routinely for primary PCI, and whether we’re not taking advantage of this 1-hour window of opportunity, said ACC Vice President Patrick T. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston. The field of STEMI has not seen a trial of this type for many years, he said.

A list of these and other late-breaking clinical trial presentations can be found on the ACC.13 website.

Dr. Quiñones and Dr. Davies reported having no financial disclosures. Dr. Ballantyne reported receiving speaker and consulting fees and research funds from many pharmaceutical companies. Dr. O’Gara has been on the data and safety monitoring board of Lantheus Medical Imaging.

s.boschert@elsevier.com

On Twitter @sherryboschert

Several studies to be presented at the annual meeting of the American College of Cardiology March 9-11 could change clinical practices. And then there are the mummies.

That’s right, mummies. More than 100 of them. They won’t be lumbering along the hallways of San Francisco’s Moscone Center, but they could tell us whether human ancestors in different parts of the world had atherosclerosis when they died and got mummified.

Following CT scans that showed atherosclerosis was common in a previous study of 52 Egyptian mummies (JACC Cardiovasc. Imaging 2011;4:315-27), investigators have imaged more than 100 mummies of people who lived 3,800 years ago in different cultures around the world. The findings should advance understanding of atherosclerosis in human civilization, ACC.13 Chairman Dr. Miguel A. Quiñones said in a teleconference preview for the press.

Some practice-changing news could come from some of the 22 late-breaking clinical trials and 2,130 abstracts accepted for presentation at the meeting, starting with highly anticipated results from a study of an intervention for atrial fibrillation, said Dr. Quiñones, chair of the department of cardiology in the Methodist Hospital System, Houston, and professor of medicine at Weill Cornell Medical College, New York.

He and a roster of other ACC officials provided these highlights:

• PREVAIL trial: Some of the most anticipated results will come from a trial of elderly patients with atrial fibrillation who were randomized to treatment with a device that allows an electrophysiologist to seal the left atrial appendage (LAA) or to conventional treatment with warfarin to reduce the risk of clots and stroke. For the nearly 1 in 10 U.S. residents aged in their 80s and 90s with atrial fibrillation, a frail physical status puts them at risk of falling, which can cause problematic bleeding if they’re being treated with anticoagulants.

Dr. Quiñones said that he expects the results of the PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients with Atrial Fibrillation Versus Long-term Warfarin Therapy) trial to be "extremely powerful in knowing whether this type of therapy is warranted in a selected group of patients with atrial fibrillation."

• RELAX trial: Treatment for heart failure in patients with a normal ejection fraction hasn’t advanced significantly in 10-15 years, but the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial could change that, he said. Roughly half of patients with heart failure have a normal ejection fraction, which is increasingly common. The trial studied whether the phosphodiesterase inhibitor sildenafil (Viagra) can improve the relaxation functions of the heart and improve clinical outcomes in these patients who have preserved pumping action but fibroses and stiffness in the heart that produce the symptoms of heart failure.

"Will this new class of agents be a breakthrough in the treatment of a disease that is very important for public health, the cost of health care, and management of diseases?" he asked.

• TACT trial: Preliminary results of TACT (Randomized Comparison of High-dose Oral Vitamins vs. Placebo in the Trial to Assess Chelation Therapy), reported at the annual meeting of the American Heart Association last fall, suggested that chelation therapy for atherosclerosis might be beneficial. Investigators will report results of treatment with chelation, high-dose oral vitamins, or placebo, alone or in combination with each other. The results "could be a game changer," Dr. Quiñones said.

• HPS2-THRIVE trial: This study of whether adding niacin and laropiprant to statins is better than statins alone in preventing future myocardial infarction in patients with previous MI or heart disease failed to reach its primary endpoint, Merck announced in late 2012. But the data on more than 25,000 patients provides enough power for potentially useful subgroup analyses, ACC.13 cochair Dr. Christie M. Ballantyne said. The cohort as a whole had low LDL levels at the start of HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events, but U.S. adults tend to have high LDL levels. Subgroup analyses may or may not show a beneficial effect of niacin/laropiprant in some populations, though it will be impossible to say whether any effect is due to the niacin or to laropiprant, which is given to reduce the side effect of flushing caused by niacin, said Dr. Ballantyne, director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, Houston.

• PEITHO trial: Results of the PEITHO (Pulmonary Embolism Thrombolysis) study are of particular interest after tennis star Venus Williams had to drop off the competitive circuit due to pulmonary embolus. The study randomized about 1,000 patients with acute pulmonary embolism in 13 countries to anticoagulation treatment with heparin alone or to heparin plus the clot-busting agent tenecteplase. "The results will help guide therapy and probably will influence the next set of chest guidelines," said ACC.13 cochair Dr. Mark G. Davies, a senior member at the Methodist Hospital Research Institute, Houston.

• Off-pump CABG: A Monday morning session combines three late-breaking trials comparing off-pump and on-pump coronary artery bypass grafting (CABG) that "probably will lead to a very spirited discussion," Dr. Davies said. One of them – the PRAGUE-6 (Off-Pump Versus On-Pump Coronary Artery Bypass Graft Surgery in High-Risk Patients) trial – could be one of the most significant presentations at the meeting, he suggested. Elderly patients were the focus of the GOPCABE (German Off Pump Coronary Artery Bypass Grafting in Elderly Patients) study. In addition, 1-year results will be presented from the CORONARY (Coronary Artery Bypass Grafting Surgery Off or On Pump Revascularization) study.

• STREAM trial: Guidelines recommend that patients with acute ST-elevation MI who present to a facility that does not perform percutaneous coronary intervention be transferred to a PCI-capable facility if the procedure can be performed within 2 hours of first medical contact. But rural residents don’t live within a stone’s throw of a catheterization lab, and even urban traffic congestion can block this strategy. The multinational STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial compared this routine-transfer strategy with routine administration of a potent bolus dose of a fibrinolytic agent if PCI cannot be performed within 1 hour, instead of the usual 2-hour window.

"This gets to the question of whether we have embedded an unnecessary and potentially dangerous time delay in a patient’s total ischemic period by stipulating that all patients should be transferred routinely for primary PCI, and whether we’re not taking advantage of this 1-hour window of opportunity, said ACC Vice President Patrick T. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston. The field of STEMI has not seen a trial of this type for many years, he said.

A list of these and other late-breaking clinical trial presentations can be found on the ACC.13 website.

Dr. Quiñones and Dr. Davies reported having no financial disclosures. Dr. Ballantyne reported receiving speaker and consulting fees and research funds from many pharmaceutical companies. Dr. O’Gara has been on the data and safety monitoring board of Lantheus Medical Imaging.

s.boschert@elsevier.com

On Twitter @sherryboschert