Hematology Times

Blood for transfusion

Photo from UAB Hospital

A class of small-molecule ice recrystallization inhibitors could improve the cryopreservation of red blood cells (RBCs) intended for transfusion, according to researchers.

The team said these molecules can decrease the time needed to thaw cryopreserved RBCs, thereby reducing transfusion wait times.

But the molecules also protect RBCs from injury during cryopreservation and reduce the risk of post-thaw hemolysis.

Robert N. Ben, PhD, of the University of Ottawa in Ontario, Canada, and his colleagues conducted this research and detailed the results in the journal ACS Omega.

The researchers began with a class of glucose-based molecules they had previously found to be cryoprotective.

The team set out to determine whether these molecules, known as O-aryl-glycosides, could potentially reduce the time needed to process frozen RBCs.

They found that changes in the structure of O-aryl-glycosides affect their ability to inhibit ice recrystallization and protect against cryoinjury. But 3 O-aryl-glycosides—β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal—proved particularly effective in these areas.

The researchers said low concentrations of β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal provided “high post-thaw RBC integrity” and reduced the needed concentration of glycerol from 40% to between 10% and 15%.

The highest post-thaw integrity observed in slow freezing conditions was with β-pBrPh-Glc and β-pBrPh-Gal. The post-thaw integrity was 65% with 55 mM of β-pBrPh-Gal and 67% with 30 mM of β-pBrPh-Glc.

The researchers noted that these molecules were “very effective” in rapid freezing conditions as well. And the addition of glycerol improved post-thaw RBC integrity.

Combining 30 mM of either molecule with 15% glycerol resulted in almost 95% post-thaw RBC integrity, whereas 15% glycerol alone provides 75% post-thaw integrity.

The researchers said 30 mM of β-pBrPh-Glc was even “highly effective” in preventing post-thaw hemolysis with a glycerol concentration of 10%. In this case, the post-thaw integrity was 67%, whereas 10% glycerol alone provides 23% post-thaw integrity.

The researchers noted that lowering the amount of glycerol needed during the cryopreservation process could help minimize the time required to prepare thawed RBCs for transfusion and provide patients with faster access to cryopreserved RBCs.

The team added that O-aryl-glycosides are structurally simple and amenable to large-scale preparation for use in cryopreservation.

Blood for transfusion

Photo from UAB Hospital

A class of small-molecule ice recrystallization inhibitors could improve the cryopreservation of red blood cells (RBCs) intended for transfusion, according to researchers.

The team said these molecules can decrease the time needed to thaw cryopreserved RBCs, thereby reducing transfusion wait times.

But the molecules also protect RBCs from injury during cryopreservation and reduce the risk of post-thaw hemolysis.

Robert N. Ben, PhD, of the University of Ottawa in Ontario, Canada, and his colleagues conducted this research and detailed the results in the journal ACS Omega.

The researchers began with a class of glucose-based molecules they had previously found to be cryoprotective.

The team set out to determine whether these molecules, known as O-aryl-glycosides, could potentially reduce the time needed to process frozen RBCs.

They found that changes in the structure of O-aryl-glycosides affect their ability to inhibit ice recrystallization and protect against cryoinjury. But 3 O-aryl-glycosides—β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal—proved particularly effective in these areas.

The researchers said low concentrations of β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal provided “high post-thaw RBC integrity” and reduced the needed concentration of glycerol from 40% to between 10% and 15%.

The highest post-thaw integrity observed in slow freezing conditions was with β-pBrPh-Glc and β-pBrPh-Gal. The post-thaw integrity was 65% with 55 mM of β-pBrPh-Gal and 67% with 30 mM of β-pBrPh-Glc.

The researchers noted that these molecules were “very effective” in rapid freezing conditions as well. And the addition of glycerol improved post-thaw RBC integrity.

Combining 30 mM of either molecule with 15% glycerol resulted in almost 95% post-thaw RBC integrity, whereas 15% glycerol alone provides 75% post-thaw integrity.

The researchers said 30 mM of β-pBrPh-Glc was even “highly effective” in preventing post-thaw hemolysis with a glycerol concentration of 10%. In this case, the post-thaw integrity was 67%, whereas 10% glycerol alone provides 23% post-thaw integrity.

The researchers noted that lowering the amount of glycerol needed during the cryopreservation process could help minimize the time required to prepare thawed RBCs for transfusion and provide patients with faster access to cryopreserved RBCs.

The team added that O-aryl-glycosides are structurally simple and amenable to large-scale preparation for use in cryopreservation.

Blood for transfusion

Photo from UAB Hospital

A class of small-molecule ice recrystallization inhibitors could improve the cryopreservation of red blood cells (RBCs) intended for transfusion, according to researchers.

The team said these molecules can decrease the time needed to thaw cryopreserved RBCs, thereby reducing transfusion wait times.

But the molecules also protect RBCs from injury during cryopreservation and reduce the risk of post-thaw hemolysis.

Robert N. Ben, PhD, of the University of Ottawa in Ontario, Canada, and his colleagues conducted this research and detailed the results in the journal ACS Omega.

The researchers began with a class of glucose-based molecules they had previously found to be cryoprotective.

The team set out to determine whether these molecules, known as O-aryl-glycosides, could potentially reduce the time needed to process frozen RBCs.

They found that changes in the structure of O-aryl-glycosides affect their ability to inhibit ice recrystallization and protect against cryoinjury. But 3 O-aryl-glycosides—β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal—proved particularly effective in these areas.

The researchers said low concentrations of β-PMP-Glc, β-pBrPh-Glc, and β-pBrPh-Gal provided “high post-thaw RBC integrity” and reduced the needed concentration of glycerol from 40% to between 10% and 15%.

The highest post-thaw integrity observed in slow freezing conditions was with β-pBrPh-Glc and β-pBrPh-Gal. The post-thaw integrity was 65% with 55 mM of β-pBrPh-Gal and 67% with 30 mM of β-pBrPh-Glc.

The researchers noted that these molecules were “very effective” in rapid freezing conditions as well. And the addition of glycerol improved post-thaw RBC integrity.

Combining 30 mM of either molecule with 15% glycerol resulted in almost 95% post-thaw RBC integrity, whereas 15% glycerol alone provides 75% post-thaw integrity.

The researchers said 30 mM of β-pBrPh-Glc was even “highly effective” in preventing post-thaw hemolysis with a glycerol concentration of 10%. In this case, the post-thaw integrity was 67%, whereas 10% glycerol alone provides 23% post-thaw integrity.

The researchers noted that lowering the amount of glycerol needed during the cryopreservation process could help minimize the time required to prepare thawed RBCs for transfusion and provide patients with faster access to cryopreserved RBCs.

The team added that O-aryl-glycosides are structurally simple and amenable to large-scale preparation for use in cryopreservation.

Micrograph showing MF

Two phase 3 trials have shown mixed results in myelofibrosis (MF) patients receiving the JAK inhibitor momelotinib, according to Gilead Sciences, Inc., the company developing the drug.

In the SIMPLIFY-1 study, momelotinib proved non-inferior to ruxolitinib when it came to the study’s primary endpoint but not its key secondary

endpoint.

In the SIMPLIFY-2 trial, momelotinib was not superior to best available therapy (BAT) with regard to the primary endpoint.

However, there were differences in favor of momelotinib when it came to some secondary endpoints.

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, Inc.

“We plan to discuss these results with regulatory authorities to determine the next steps.”

About the studies

The SIMPLIFY studies are randomized, phase 3 trials designed to evaluate momelotinib in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. The trials have the same primary and secondary endpoints.

The primary efficacy endpoint is splenic response rate at week 24 (SRR24), defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume at week 24, as measured by MRI or CT scan.

Secondary endpoints include:

• Response rate in total symptom score (TSS) at week 24, defined as the proportion of patients achieving ≥ 50% reduction in symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score diary
• The proportion of patients who are transfusion-independent at week 24, defined as no red blood cell transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks
• The proportion who are transfusion-dependent at week 24, defined as at least 4 units of red blood cell transfusion or hemoglobin level below 8 g/dL in the prior 8 weeks
• The rate of red blood cell transfusion through week 24.

SIMPLIFY-1 trial

In SIMPLIFY-1, a double-blind, active-controlled study, 432 MF patients who had not previously been treated with a JAK inhibitor were randomized (1:1) to receive momelotinib or ruxolitinib for 24 weeks.

The study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for SRR24. The incidence of SRR24 was 26.5% in the momelotinib arm and 29.0% in the ruxolitinib arm (95% CI: -11.2% to +5.6%; P=0.011).

However, non-inferiority was not achieved for the key secondary endpoint of response rate in TSS.

Greater improvements in all 3 anemia-related secondary endpoints—transfusion independence, transfusion dependence, and transfusion rate—were observed in patients receiving momelotinib compared to ruxolitinib.

However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these 3 secondary endpoints.

During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness, and nausea.

The most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache, and dizziness.

Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade), compared to 5% of ruxolitinib-treated patients. There was no grade 3 or higher peripheral neuropathy in momelotinib-treated patients, but there was 1 case in the ruxolitinib arm.

SIMPLIFY-2 trial

In SIMPLIFY-2, 156 patients previously treated with, but not refractory to, ruxolitinib were randomized (2:1) to receive momelotinib or BAT for 24 weeks.

Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib. The remainder of patients received chemotherapy, interferon, corticosteroids, other therapies, or some combination thereof.

The study’s primary endpoint was not met. Momelotinib did not prove superior to BAT with regard to SRR24. The incidence of SRR24 was 6.7% in the momelotinib arm and 5.8% in the BAT arm (95% CI: -8.9% to +10.2%; P=0.90).

Differences in favor of momelotinib were observed for the secondary endpoints of TSS and transfusion independence. However, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Gilead did not release safety data from this trial. The company said detailed results from both SIMPLIFY studies will be submitted for presentation at upcoming scientific conferences.

Micrograph showing MF

Two phase 3 trials have shown mixed results in myelofibrosis (MF) patients receiving the JAK inhibitor momelotinib, according to Gilead Sciences, Inc., the company developing the drug.

In the SIMPLIFY-1 study, momelotinib proved non-inferior to ruxolitinib when it came to the study’s primary endpoint but not its key secondary

endpoint.

In the SIMPLIFY-2 trial, momelotinib was not superior to best available therapy (BAT) with regard to the primary endpoint.

However, there were differences in favor of momelotinib when it came to some secondary endpoints.

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, Inc.

“We plan to discuss these results with regulatory authorities to determine the next steps.”

About the studies

The SIMPLIFY studies are randomized, phase 3 trials designed to evaluate momelotinib in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. The trials have the same primary and secondary endpoints.

The primary efficacy endpoint is splenic response rate at week 24 (SRR24), defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume at week 24, as measured by MRI or CT scan.

Secondary endpoints include:

• Response rate in total symptom score (TSS) at week 24, defined as the proportion of patients achieving ≥ 50% reduction in symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score diary
• The proportion of patients who are transfusion-independent at week 24, defined as no red blood cell transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks
• The proportion who are transfusion-dependent at week 24, defined as at least 4 units of red blood cell transfusion or hemoglobin level below 8 g/dL in the prior 8 weeks
• The rate of red blood cell transfusion through week 24.

SIMPLIFY-1 trial

In SIMPLIFY-1, a double-blind, active-controlled study, 432 MF patients who had not previously been treated with a JAK inhibitor were randomized (1:1) to receive momelotinib or ruxolitinib for 24 weeks.

The study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for SRR24. The incidence of SRR24 was 26.5% in the momelotinib arm and 29.0% in the ruxolitinib arm (95% CI: -11.2% to +5.6%; P=0.011).

However, non-inferiority was not achieved for the key secondary endpoint of response rate in TSS.

Greater improvements in all 3 anemia-related secondary endpoints—transfusion independence, transfusion dependence, and transfusion rate—were observed in patients receiving momelotinib compared to ruxolitinib.

However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these 3 secondary endpoints.

During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness, and nausea.

The most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache, and dizziness.

Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade), compared to 5% of ruxolitinib-treated patients. There was no grade 3 or higher peripheral neuropathy in momelotinib-treated patients, but there was 1 case in the ruxolitinib arm.

SIMPLIFY-2 trial

In SIMPLIFY-2, 156 patients previously treated with, but not refractory to, ruxolitinib were randomized (2:1) to receive momelotinib or BAT for 24 weeks.

Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib. The remainder of patients received chemotherapy, interferon, corticosteroids, other therapies, or some combination thereof.

The study’s primary endpoint was not met. Momelotinib did not prove superior to BAT with regard to SRR24. The incidence of SRR24 was 6.7% in the momelotinib arm and 5.8% in the BAT arm (95% CI: -8.9% to +10.2%; P=0.90).

Differences in favor of momelotinib were observed for the secondary endpoints of TSS and transfusion independence. However, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Gilead did not release safety data from this trial. The company said detailed results from both SIMPLIFY studies will be submitted for presentation at upcoming scientific conferences.

Micrograph showing MF

Two phase 3 trials have shown mixed results in myelofibrosis (MF) patients receiving the JAK inhibitor momelotinib, according to Gilead Sciences, Inc., the company developing the drug.

In the SIMPLIFY-1 study, momelotinib proved non-inferior to ruxolitinib when it came to the study’s primary endpoint but not its key secondary

endpoint.

In the SIMPLIFY-2 trial, momelotinib was not superior to best available therapy (BAT) with regard to the primary endpoint.

However, there were differences in favor of momelotinib when it came to some secondary endpoints.

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, Inc.

“We plan to discuss these results with regulatory authorities to determine the next steps.”

About the studies

The SIMPLIFY studies are randomized, phase 3 trials designed to evaluate momelotinib in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. The trials have the same primary and secondary endpoints.

The primary efficacy endpoint is splenic response rate at week 24 (SRR24), defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume at week 24, as measured by MRI or CT scan.

Secondary endpoints include:

• Response rate in total symptom score (TSS) at week 24, defined as the proportion of patients achieving ≥ 50% reduction in symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score diary
• The proportion of patients who are transfusion-independent at week 24, defined as no red blood cell transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks
• The proportion who are transfusion-dependent at week 24, defined as at least 4 units of red blood cell transfusion or hemoglobin level below 8 g/dL in the prior 8 weeks
• The rate of red blood cell transfusion through week 24.

SIMPLIFY-1 trial

In SIMPLIFY-1, a double-blind, active-controlled study, 432 MF patients who had not previously been treated with a JAK inhibitor were randomized (1:1) to receive momelotinib or ruxolitinib for 24 weeks.

The study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for SRR24. The incidence of SRR24 was 26.5% in the momelotinib arm and 29.0% in the ruxolitinib arm (95% CI: -11.2% to +5.6%; P=0.011).

However, non-inferiority was not achieved for the key secondary endpoint of response rate in TSS.

Greater improvements in all 3 anemia-related secondary endpoints—transfusion independence, transfusion dependence, and transfusion rate—were observed in patients receiving momelotinib compared to ruxolitinib.

However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these 3 secondary endpoints.

During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness, and nausea.

The most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache, and dizziness.

Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade), compared to 5% of ruxolitinib-treated patients. There was no grade 3 or higher peripheral neuropathy in momelotinib-treated patients, but there was 1 case in the ruxolitinib arm.

SIMPLIFY-2 trial

In SIMPLIFY-2, 156 patients previously treated with, but not refractory to, ruxolitinib were randomized (2:1) to receive momelotinib or BAT for 24 weeks.

Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib. The remainder of patients received chemotherapy, interferon, corticosteroids, other therapies, or some combination thereof.

The study’s primary endpoint was not met. Momelotinib did not prove superior to BAT with regard to SRR24. The incidence of SRR24 was 6.7% in the momelotinib arm and 5.8% in the BAT arm (95% CI: -8.9% to +10.2%; P=0.90).

Differences in favor of momelotinib were observed for the secondary endpoints of TSS and transfusion independence. However, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Gilead did not release safety data from this trial. The company said detailed results from both SIMPLIFY studies will be submitted for presentation at upcoming scientific conferences.

A nurse and a doctor

caring for a patient in

an intensive care unit

The American Association of Critical-Care Nurses (AACN) has released updated resources aimed at helping nurses prevent serious complications facing critically ill patients.

The resources, or “practice alerts,” address venous thromboembolism (VTE), delirium, and catheter-associated urinary tract infections (CAUTIs).

Each alert outlines the scope of the problem, summarizes the expected nursing practice, and provides supporting evidence and research.

These documents are available on the AACN website.

The VTE practice alert, “Preventing Venous Thromboembolism in Adults,” notes that VTE affects approximately 900,000 adult patients in the US annually and results in an estimated 300,000 deaths. Furthermore, VTE prevalence is predicted to more than double in the next 35 years.

The document also reviews risk factors for VTE and methods of VTE prophylaxis, including medications and compression devices.

The CAUTI practice alert, “Prevention of Catheter-Associated Urinary Tract Infections in Adults,” notes that urinary tract infections are the most common healthcare-associated infection, and prolonged indwelling catheterization is the major risk factor for CAUTIs.

The document outlines preliminary and ongoing assessment, documentation, and adherence to infection control protocols.

The delirium practice alert, “Assessment and Management of Delirium Across the Life Span,” states that delirium affects up to 80% of critically ill patients in the US, with associated annual costs between $4 billion and $16 billion.

The document reviews risk factors for pediatric and adult patients and the use of validated tools to assess for delirium.

According to AACN, each practice alert is supported by authoritative evidence and seeks to ensure excellence in practice along with promotion of a safe and humane work environment.

Topics address both nursing and interprofessional activities of importance for patients in acute and critical care environments. Some alerts include additional resources for staff education and performance-improvement activities.

A nurse and a doctor

caring for a patient in

an intensive care unit

The American Association of Critical-Care Nurses (AACN) has released updated resources aimed at helping nurses prevent serious complications facing critically ill patients.

The resources, or “practice alerts,” address venous thromboembolism (VTE), delirium, and catheter-associated urinary tract infections (CAUTIs).

Each alert outlines the scope of the problem, summarizes the expected nursing practice, and provides supporting evidence and research.

These documents are available on the AACN website.

The VTE practice alert, “Preventing Venous Thromboembolism in Adults,” notes that VTE affects approximately 900,000 adult patients in the US annually and results in an estimated 300,000 deaths. Furthermore, VTE prevalence is predicted to more than double in the next 35 years.

The document also reviews risk factors for VTE and methods of VTE prophylaxis, including medications and compression devices.

The CAUTI practice alert, “Prevention of Catheter-Associated Urinary Tract Infections in Adults,” notes that urinary tract infections are the most common healthcare-associated infection, and prolonged indwelling catheterization is the major risk factor for CAUTIs.

The document outlines preliminary and ongoing assessment, documentation, and adherence to infection control protocols.

The delirium practice alert, “Assessment and Management of Delirium Across the Life Span,” states that delirium affects up to 80% of critically ill patients in the US, with associated annual costs between $4 billion and $16 billion.

The document reviews risk factors for pediatric and adult patients and the use of validated tools to assess for delirium.

According to AACN, each practice alert is supported by authoritative evidence and seeks to ensure excellence in practice along with promotion of a safe and humane work environment.

Topics address both nursing and interprofessional activities of importance for patients in acute and critical care environments. Some alerts include additional resources for staff education and performance-improvement activities.

A nurse and a doctor

caring for a patient in

an intensive care unit

The American Association of Critical-Care Nurses (AACN) has released updated resources aimed at helping nurses prevent serious complications facing critically ill patients.

The resources, or “practice alerts,” address venous thromboembolism (VTE), delirium, and catheter-associated urinary tract infections (CAUTIs).

Each alert outlines the scope of the problem, summarizes the expected nursing practice, and provides supporting evidence and research.

These documents are available on the AACN website.

The VTE practice alert, “Preventing Venous Thromboembolism in Adults,” notes that VTE affects approximately 900,000 adult patients in the US annually and results in an estimated 300,000 deaths. Furthermore, VTE prevalence is predicted to more than double in the next 35 years.

The document also reviews risk factors for VTE and methods of VTE prophylaxis, including medications and compression devices.

The CAUTI practice alert, “Prevention of Catheter-Associated Urinary Tract Infections in Adults,” notes that urinary tract infections are the most common healthcare-associated infection, and prolonged indwelling catheterization is the major risk factor for CAUTIs.

The document outlines preliminary and ongoing assessment, documentation, and adherence to infection control protocols.

The delirium practice alert, “Assessment and Management of Delirium Across the Life Span,” states that delirium affects up to 80% of critically ill patients in the US, with associated annual costs between $4 billion and $16 billion.

The document reviews risk factors for pediatric and adult patients and the use of validated tools to assess for delirium.

According to AACN, each practice alert is supported by authoritative evidence and seeks to ensure excellence in practice along with promotion of a safe and humane work environment.

Topics address both nursing and interprofessional activities of importance for patients in acute and critical care environments. Some alerts include additional resources for staff education and performance-improvement activities.

Warfarin tablets

NEW ORLEANS—Many US patients who are candidates for treatment with oral anticoagulants (OACs) are not actually receiving these drugs, a large study suggests.

Investigators analyzed information on nearly 1.6 million hospital admissions of patients with atrial fibrillation who were candidates for OAC treatment according to guideline recommendations.

The data showed that only 46% of these patients actually received an OAC at discharge.

“This low rate of OAC use in hospitalized patients highlights an important opportunity to improve care in atrial fibrillation patients,” said Sean Pokorney, MD, of Duke University School of Medicine in Durham, North Carolina.

Dr Pokorney and his colleagues presented this research at the American Heart Association Scientific Sessions (abstract 17636).

The study was supported by Janssen Scientific Affairs, and some of the study’s investigators reported financial relationships with Janssen.

The investigators analyzed data on 1,579,456 hospital admissions across the US, occurring between January 2010 and June 2015, in which patients were treated for atrial fibrillation. The information was taken from the Premier Healthcare Database, which includes data for 1 in 5 hospital discharges in the US.

The patients analyzed were at least 40 years old and stayed in the hospital for at least 1 day. They also had a CHA₂DS₂-VASc stroke risk score of 2 or higher and were therefore candidates for treatment with an OAC, according to guideline recommendations from the American Heart Association and American College of Cardiology.

The CHA₂DS₂-VASc stroke risk score considers several factors, including age, sex, and history of congestive heart failure, stroke, diabetes, hypertension, and vascular disease.

“[I]n certain cases, it may not be safe for patients with a high stroke risk score to take blood thinners because of complications that could arise,” Dr Pokorney noted. “Still, we think 50% is too low and that there are thousands of preventable strokes happening in the United States each year because of the low rates of OAC usage.”

Dr Pokorney noted that use of OACs hovered just below 50% across several subgroups in the study.

OAC use by subgroup

The proportion of OAC use was:

• 46% overall
• 47% for patients with prior stroke
• 45% for females
• 46% for non-whites
• 47% for patients with hypertension
• 49% for those with diabetes
• 45% for patients with chronic kidney disease
• 35% for those with dementia
• 38% for patients with a history of falls
• 47% for those younger than 55
• 50% for ages 55-64 and 65-74
• 49% for ages 75-84
• 38% for patients 85 and older.

“This study identified a gap in care and is a critical first step in raising questions about how we can optimize the OAC decision-making process that atrial fibrillation patients and their providers are engaging in during a hospital stay and at the point of discharge,” Dr Pokorney said.

Barriers to OAC use

Dr Pokorney and his colleagues hope to conduct further research to determine what barriers to OAC use might exist. Dr Pokorney said possible barriers could include:

• A lack of understanding about atrial fibrillation and the risk of stroke or fear of using OACs among patients
• Knowledge deficits about stroke prevention or overemphasis of the risks of OACs among healthcare providers
• A view that OAC use is an outpatient issue, rather than an inpatient issue, among healthcare providers and systems.

Study limitations

The data showed whether patients were provided an OAC during their hospital stays. For the purposes of the study, the investigators assumed that those inpatients who were on an OAC within 24 hours of hospital discharge were also prescribed an OAC upon discharge.

However, there was no way to verify that a prescription was indeed made or filled after discharge. Additionally, although the investigators tried to exclude patients who were not candidates for OACs because of the risk of complications, there is the possibility that some remained in the study’s sample.

Warfarin tablets

NEW ORLEANS—Many US patients who are candidates for treatment with oral anticoagulants (OACs) are not actually receiving these drugs, a large study suggests.

Investigators analyzed information on nearly 1.6 million hospital admissions of patients with atrial fibrillation who were candidates for OAC treatment according to guideline recommendations.

The data showed that only 46% of these patients actually received an OAC at discharge.

“This low rate of OAC use in hospitalized patients highlights an important opportunity to improve care in atrial fibrillation patients,” said Sean Pokorney, MD, of Duke University School of Medicine in Durham, North Carolina.

Dr Pokorney and his colleagues presented this research at the American Heart Association Scientific Sessions (abstract 17636).

The study was supported by Janssen Scientific Affairs, and some of the study’s investigators reported financial relationships with Janssen.

The investigators analyzed data on 1,579,456 hospital admissions across the US, occurring between January 2010 and June 2015, in which patients were treated for atrial fibrillation. The information was taken from the Premier Healthcare Database, which includes data for 1 in 5 hospital discharges in the US.

The patients analyzed were at least 40 years old and stayed in the hospital for at least 1 day. They also had a CHA₂DS₂-VASc stroke risk score of 2 or higher and were therefore candidates for treatment with an OAC, according to guideline recommendations from the American Heart Association and American College of Cardiology.

The CHA₂DS₂-VASc stroke risk score considers several factors, including age, sex, and history of congestive heart failure, stroke, diabetes, hypertension, and vascular disease.

“[I]n certain cases, it may not be safe for patients with a high stroke risk score to take blood thinners because of complications that could arise,” Dr Pokorney noted. “Still, we think 50% is too low and that there are thousands of preventable strokes happening in the United States each year because of the low rates of OAC usage.”

Dr Pokorney noted that use of OACs hovered just below 50% across several subgroups in the study.

OAC use by subgroup

The proportion of OAC use was:

• 46% overall
• 47% for patients with prior stroke
• 45% for females
• 46% for non-whites
• 47% for patients with hypertension
• 49% for those with diabetes
• 45% for patients with chronic kidney disease
• 35% for those with dementia
• 38% for patients with a history of falls
• 47% for those younger than 55
• 50% for ages 55-64 and 65-74
• 49% for ages 75-84
• 38% for patients 85 and older.

“This study identified a gap in care and is a critical first step in raising questions about how we can optimize the OAC decision-making process that atrial fibrillation patients and their providers are engaging in during a hospital stay and at the point of discharge,” Dr Pokorney said.

Barriers to OAC use

Dr Pokorney and his colleagues hope to conduct further research to determine what barriers to OAC use might exist. Dr Pokorney said possible barriers could include:

• A lack of understanding about atrial fibrillation and the risk of stroke or fear of using OACs among patients
• Knowledge deficits about stroke prevention or overemphasis of the risks of OACs among healthcare providers
• A view that OAC use is an outpatient issue, rather than an inpatient issue, among healthcare providers and systems.

Study limitations

The data showed whether patients were provided an OAC during their hospital stays. For the purposes of the study, the investigators assumed that those inpatients who were on an OAC within 24 hours of hospital discharge were also prescribed an OAC upon discharge.

However, there was no way to verify that a prescription was indeed made or filled after discharge. Additionally, although the investigators tried to exclude patients who were not candidates for OACs because of the risk of complications, there is the possibility that some remained in the study’s sample.

Warfarin tablets

NEW ORLEANS—Many US patients who are candidates for treatment with oral anticoagulants (OACs) are not actually receiving these drugs, a large study suggests.

Investigators analyzed information on nearly 1.6 million hospital admissions of patients with atrial fibrillation who were candidates for OAC treatment according to guideline recommendations.

The data showed that only 46% of these patients actually received an OAC at discharge.

“This low rate of OAC use in hospitalized patients highlights an important opportunity to improve care in atrial fibrillation patients,” said Sean Pokorney, MD, of Duke University School of Medicine in Durham, North Carolina.

Dr Pokorney and his colleagues presented this research at the American Heart Association Scientific Sessions (abstract 17636).

The study was supported by Janssen Scientific Affairs, and some of the study’s investigators reported financial relationships with Janssen.

The investigators analyzed data on 1,579,456 hospital admissions across the US, occurring between January 2010 and June 2015, in which patients were treated for atrial fibrillation. The information was taken from the Premier Healthcare Database, which includes data for 1 in 5 hospital discharges in the US.

The patients analyzed were at least 40 years old and stayed in the hospital for at least 1 day. They also had a CHA₂DS₂-VASc stroke risk score of 2 or higher and were therefore candidates for treatment with an OAC, according to guideline recommendations from the American Heart Association and American College of Cardiology.

The CHA₂DS₂-VASc stroke risk score considers several factors, including age, sex, and history of congestive heart failure, stroke, diabetes, hypertension, and vascular disease.

“[I]n certain cases, it may not be safe for patients with a high stroke risk score to take blood thinners because of complications that could arise,” Dr Pokorney noted. “Still, we think 50% is too low and that there are thousands of preventable strokes happening in the United States each year because of the low rates of OAC usage.”

Dr Pokorney noted that use of OACs hovered just below 50% across several subgroups in the study.

OAC use by subgroup

The proportion of OAC use was:

• 46% overall
• 47% for patients with prior stroke
• 45% for females
• 46% for non-whites
• 47% for patients with hypertension
• 49% for those with diabetes
• 45% for patients with chronic kidney disease
• 35% for those with dementia
• 38% for patients with a history of falls
• 47% for those younger than 55
• 50% for ages 55-64 and 65-74
• 49% for ages 75-84
• 38% for patients 85 and older.

“This study identified a gap in care and is a critical first step in raising questions about how we can optimize the OAC decision-making process that atrial fibrillation patients and their providers are engaging in during a hospital stay and at the point of discharge,” Dr Pokorney said.

Barriers to OAC use

Dr Pokorney and his colleagues hope to conduct further research to determine what barriers to OAC use might exist. Dr Pokorney said possible barriers could include:

• A lack of understanding about atrial fibrillation and the risk of stroke or fear of using OACs among patients
• Knowledge deficits about stroke prevention or overemphasis of the risks of OACs among healthcare providers
• A view that OAC use is an outpatient issue, rather than an inpatient issue, among healthcare providers and systems.

Study limitations

The data showed whether patients were provided an OAC during their hospital stays. For the purposes of the study, the investigators assumed that those inpatients who were on an OAC within 24 hours of hospital discharge were also prescribed an OAC upon discharge.

However, there was no way to verify that a prescription was indeed made or filled after discharge. Additionally, although the investigators tried to exclude patients who were not candidates for OACs because of the risk of complications, there is the possibility that some remained in the study’s sample.

Piglet

Photo courtesy of USDA

Bioengineers have developed an injectable material that may provide a better way to stop bleeding in injured patients, even those taking anticoagulants and individuals with coagulopathy.

The so-called shear-thinning biomaterial (STB) is composed of gelatin and silicate nanoplatelet hydrogel.

It can be injected through a catheter or needle to occlude blood vessels.

The STB demonstrated efficacy in vitro and in experiments with mice and pigs.

“This work is an example of how bioengineering can help address the challenges that clinicians and patients face,” said Ali Khademhosseini, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“Our work thus far has been in the lab, but we are on a translational path to bring this new biomaterial for embolization to the clinic to improve patient care.”

Dr Khademhosseini and his colleagues described their work with STB in Science Translational Medicine.

The researchers noted that trauma or injury often leads to excessive bleeding that can result in death.

Embolic materials, such as metallic coils or liquid embolic agents, are commonly used to block injured blood vessels and stem bleeding, but these materials can cause complications such as coil migration or breakthrough bleeding.

Because these materials rely on intrinsic thrombosis, they are often ineffective in patients with severe bleeding disorders or those on anticoagulation therapy.

In search of a safer and more effective alternative, Dr Khademhosseini and his colleagues developed their STB.

The STB can be flowed into a blood vessel using a catheter, but the material is able to maintain its shape once inside the vessel, obstructing the vessel without relying on the formation of a blood clot.

In vitro, the STB performed just as well as metallic coils and was able to withstand high pressures without fragmenting or being dislodged in explant vessels.

The STB was even effective in stemming anticoagulated blood flow in vitro, suggesting that it could potentially be used in patients with bleeding disorders or those on anticoagulants.

The STB successfully blocked arteries and veins in mice and pigs, forming an impenetrable cast of the vessels that remained in place for up to 24 days.

The researchers said some of the beneficial properties of the STB include its ability to withstand pressure within the blood vessel, remain at the site of injection, and naturally degrade over time.

In addition, the STB attracted cells to migrate and deposit themselves at the site of the STB, helping to block the vessel.

The researchers noted that the individual component materials that make up the STB have been previously used in humans, which may mean a quicker path to regulatory approval.

Piglet

Photo courtesy of USDA

Bioengineers have developed an injectable material that may provide a better way to stop bleeding in injured patients, even those taking anticoagulants and individuals with coagulopathy.

The so-called shear-thinning biomaterial (STB) is composed of gelatin and silicate nanoplatelet hydrogel.

It can be injected through a catheter or needle to occlude blood vessels.

The STB demonstrated efficacy in vitro and in experiments with mice and pigs.

“This work is an example of how bioengineering can help address the challenges that clinicians and patients face,” said Ali Khademhosseini, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“Our work thus far has been in the lab, but we are on a translational path to bring this new biomaterial for embolization to the clinic to improve patient care.”

Dr Khademhosseini and his colleagues described their work with STB in Science Translational Medicine.

The researchers noted that trauma or injury often leads to excessive bleeding that can result in death.

Embolic materials, such as metallic coils or liquid embolic agents, are commonly used to block injured blood vessels and stem bleeding, but these materials can cause complications such as coil migration or breakthrough bleeding.

Because these materials rely on intrinsic thrombosis, they are often ineffective in patients with severe bleeding disorders or those on anticoagulation therapy.

In search of a safer and more effective alternative, Dr Khademhosseini and his colleagues developed their STB.

The STB can be flowed into a blood vessel using a catheter, but the material is able to maintain its shape once inside the vessel, obstructing the vessel without relying on the formation of a blood clot.

In vitro, the STB performed just as well as metallic coils and was able to withstand high pressures without fragmenting or being dislodged in explant vessels.

The STB was even effective in stemming anticoagulated blood flow in vitro, suggesting that it could potentially be used in patients with bleeding disorders or those on anticoagulants.

The STB successfully blocked arteries and veins in mice and pigs, forming an impenetrable cast of the vessels that remained in place for up to 24 days.

The researchers said some of the beneficial properties of the STB include its ability to withstand pressure within the blood vessel, remain at the site of injection, and naturally degrade over time.

In addition, the STB attracted cells to migrate and deposit themselves at the site of the STB, helping to block the vessel.

The researchers noted that the individual component materials that make up the STB have been previously used in humans, which may mean a quicker path to regulatory approval.

Piglet

Photo courtesy of USDA

Bioengineers have developed an injectable material that may provide a better way to stop bleeding in injured patients, even those taking anticoagulants and individuals with coagulopathy.

The so-called shear-thinning biomaterial (STB) is composed of gelatin and silicate nanoplatelet hydrogel.

It can be injected through a catheter or needle to occlude blood vessels.

The STB demonstrated efficacy in vitro and in experiments with mice and pigs.

“This work is an example of how bioengineering can help address the challenges that clinicians and patients face,” said Ali Khademhosseini, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“Our work thus far has been in the lab, but we are on a translational path to bring this new biomaterial for embolization to the clinic to improve patient care.”

Dr Khademhosseini and his colleagues described their work with STB in Science Translational Medicine.

The researchers noted that trauma or injury often leads to excessive bleeding that can result in death.

Embolic materials, such as metallic coils or liquid embolic agents, are commonly used to block injured blood vessels and stem bleeding, but these materials can cause complications such as coil migration or breakthrough bleeding.

Because these materials rely on intrinsic thrombosis, they are often ineffective in patients with severe bleeding disorders or those on anticoagulation therapy.

In search of a safer and more effective alternative, Dr Khademhosseini and his colleagues developed their STB.

The STB can be flowed into a blood vessel using a catheter, but the material is able to maintain its shape once inside the vessel, obstructing the vessel without relying on the formation of a blood clot.

In vitro, the STB performed just as well as metallic coils and was able to withstand high pressures without fragmenting or being dislodged in explant vessels.

The STB was even effective in stemming anticoagulated blood flow in vitro, suggesting that it could potentially be used in patients with bleeding disorders or those on anticoagulants.

The STB successfully blocked arteries and veins in mice and pigs, forming an impenetrable cast of the vessels that remained in place for up to 24 days.

The researchers said some of the beneficial properties of the STB include its ability to withstand pressure within the blood vessel, remain at the site of injection, and naturally degrade over time.

In addition, the STB attracted cells to migrate and deposit themselves at the site of the STB, helping to block the vessel.

The researchers noted that the individual component materials that make up the STB have been previously used in humans, which may mean a quicker path to regulatory approval.

The team designed a structure

with 6 arms that can be folded

and encased in a capsule.

Photo by Melanie Gonick/MIT

A new device can provide long-term, controlled drug release, according to research published in Science Translational Medicine.

Researchers tested this device—a 6-armed structure encased in a capsule—by loading it with ivermectin, an antiparasitic drug that disrupts malaria transmission by killing infected mosquitoes.

When administered to pigs, the device safely stayed in the stomach, slowly releasing ivermectin for up to 14 days.

Researchers believe this type of lasting drug delivery could help bolster the success of malaria elimination campaigns, which rely on treatment adherence and cost-effective approaches that reach large, rural populations.

The team also believes this device could be used to treat a range of other diseases, particularly those in which treatment adherence may be an issue.

“We want to make it as easy as possible for people to take their medications over a sustained period of time,” said study author C. Giovanni Traverso, MB, BChir, PhD, of the Massachusetts Institute of Technology (MIT) in Cambridge.

“When patients have to remember to take a drug every day or multiple times a day, we start to see less and less adherence to the regimen. Being able to swallow a capsule once a week or once a month could change the way we think about delivering medications.”

This research has led to the launch of Lyndra, a company that is developing this technology with a focus on diseases for which patients would benefit the most from sustained drug delivery. This includes neuropsychiatric disorders, HIV, diabetes, and epilepsy.

Designing, testing the device

To provide long-term drug delivery, the researchers designed a star-shaped device with 6 arms that can be folded inward and encased in a smooth capsule.

Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down.

After the capsule is swallowed, stomach acid dissolves the outer layer, allowing the 6-armed device to unfold.

Once the device expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract.

The drug is gradually released over a period of several days. After that, the linkers that join the arms to the core of the device dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract.

In pigs, the device slowly released ivermectin for up to 14 days without causing injury to the stomach or obstructing the passage of food, before breaking apart and passing safely out of the body.

Modeling the impact

The researchers used mathematical modeling to predict the potential impact of this drug delivery method.

The data suggested that if the device were used to deliver ivermectin, it could increase the efficacy of mass drug administration campaigns designed to fight malaria.

“What we showed is that we stand to significantly amplify the effect of those campaigns,” Dr Traverso said. “The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication.”

Potential applications

“Until now, oral drugs would almost never last for more than a day,” said study author Robert Langer, ScD, of MIT.

“This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders. There are a lot of exciting things this could someday enable.”

“This is a platform into which you can incorporate any drug,” added Mousa Jafari, PhD, of MIT. “This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration.”

This type of delivery could also help researchers run better clinical trials by making it easier for patients to take the drugs, said Shiyi Zhang, PhD, of MIT.

“It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs because, currently, a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies,” he said.

The team designed a structure

with 6 arms that can be folded

and encased in a capsule.

Photo by Melanie Gonick/MIT

A new device can provide long-term, controlled drug release, according to research published in Science Translational Medicine.

Researchers tested this device—a 6-armed structure encased in a capsule—by loading it with ivermectin, an antiparasitic drug that disrupts malaria transmission by killing infected mosquitoes.

When administered to pigs, the device safely stayed in the stomach, slowly releasing ivermectin for up to 14 days.

Researchers believe this type of lasting drug delivery could help bolster the success of malaria elimination campaigns, which rely on treatment adherence and cost-effective approaches that reach large, rural populations.

The team also believes this device could be used to treat a range of other diseases, particularly those in which treatment adherence may be an issue.

“We want to make it as easy as possible for people to take their medications over a sustained period of time,” said study author C. Giovanni Traverso, MB, BChir, PhD, of the Massachusetts Institute of Technology (MIT) in Cambridge.

“When patients have to remember to take a drug every day or multiple times a day, we start to see less and less adherence to the regimen. Being able to swallow a capsule once a week or once a month could change the way we think about delivering medications.”

This research has led to the launch of Lyndra, a company that is developing this technology with a focus on diseases for which patients would benefit the most from sustained drug delivery. This includes neuropsychiatric disorders, HIV, diabetes, and epilepsy.

Designing, testing the device

To provide long-term drug delivery, the researchers designed a star-shaped device with 6 arms that can be folded inward and encased in a smooth capsule.

Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down.

After the capsule is swallowed, stomach acid dissolves the outer layer, allowing the 6-armed device to unfold.

Once the device expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract.

The drug is gradually released over a period of several days. After that, the linkers that join the arms to the core of the device dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract.

In pigs, the device slowly released ivermectin for up to 14 days without causing injury to the stomach or obstructing the passage of food, before breaking apart and passing safely out of the body.

Modeling the impact

The researchers used mathematical modeling to predict the potential impact of this drug delivery method.

The data suggested that if the device were used to deliver ivermectin, it could increase the efficacy of mass drug administration campaigns designed to fight malaria.

“What we showed is that we stand to significantly amplify the effect of those campaigns,” Dr Traverso said. “The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication.”

Potential applications

“Until now, oral drugs would almost never last for more than a day,” said study author Robert Langer, ScD, of MIT.

“This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders. There are a lot of exciting things this could someday enable.”

“This is a platform into which you can incorporate any drug,” added Mousa Jafari, PhD, of MIT. “This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration.”

This type of delivery could also help researchers run better clinical trials by making it easier for patients to take the drugs, said Shiyi Zhang, PhD, of MIT.

“It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs because, currently, a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies,” he said.

The team designed a structure

with 6 arms that can be folded

and encased in a capsule.

Photo by Melanie Gonick/MIT

A new device can provide long-term, controlled drug release, according to research published in Science Translational Medicine.

Researchers tested this device—a 6-armed structure encased in a capsule—by loading it with ivermectin, an antiparasitic drug that disrupts malaria transmission by killing infected mosquitoes.

When administered to pigs, the device safely stayed in the stomach, slowly releasing ivermectin for up to 14 days.

Researchers believe this type of lasting drug delivery could help bolster the success of malaria elimination campaigns, which rely on treatment adherence and cost-effective approaches that reach large, rural populations.

The team also believes this device could be used to treat a range of other diseases, particularly those in which treatment adherence may be an issue.

“We want to make it as easy as possible for people to take their medications over a sustained period of time,” said study author C. Giovanni Traverso, MB, BChir, PhD, of the Massachusetts Institute of Technology (MIT) in Cambridge.

“When patients have to remember to take a drug every day or multiple times a day, we start to see less and less adherence to the regimen. Being able to swallow a capsule once a week or once a month could change the way we think about delivering medications.”

This research has led to the launch of Lyndra, a company that is developing this technology with a focus on diseases for which patients would benefit the most from sustained drug delivery. This includes neuropsychiatric disorders, HIV, diabetes, and epilepsy.

Designing, testing the device

To provide long-term drug delivery, the researchers designed a star-shaped device with 6 arms that can be folded inward and encased in a smooth capsule.

Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down.

After the capsule is swallowed, stomach acid dissolves the outer layer, allowing the 6-armed device to unfold.

Once the device expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract.

The drug is gradually released over a period of several days. After that, the linkers that join the arms to the core of the device dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract.

In pigs, the device slowly released ivermectin for up to 14 days without causing injury to the stomach or obstructing the passage of food, before breaking apart and passing safely out of the body.

Modeling the impact

The researchers used mathematical modeling to predict the potential impact of this drug delivery method.

The data suggested that if the device were used to deliver ivermectin, it could increase the efficacy of mass drug administration campaigns designed to fight malaria.

“What we showed is that we stand to significantly amplify the effect of those campaigns,” Dr Traverso said. “The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication.”

Potential applications

“Until now, oral drugs would almost never last for more than a day,” said study author Robert Langer, ScD, of MIT.

“This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders. There are a lot of exciting things this could someday enable.”

“This is a platform into which you can incorporate any drug,” added Mousa Jafari, PhD, of MIT. “This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration.”

This type of delivery could also help researchers run better clinical trials by making it easier for patients to take the drugs, said Shiyi Zhang, PhD, of MIT.

“It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs because, currently, a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies,” he said.

Study authors Hui Ding

and Patrick Harran with

a model of DZ-2384

Photo courtesy of

Reed Hutchinson/UCLA

A new compound holds promise for treating leukemia and other cancers, according to researchers.

The compound, DZ-2384, is a synthetic version of diazonamide A, a toxin isolated from a marine animal.

DZ-2384 is a microtubule-targeting agent (MTA). It binds to and alters the stability of microtubules, disrupting the normal function of the mitotic spindle and arresting cell-cycle progression at mitosis, ultimately leading to cell death.

However, researchers found that DZ-2384 behaves somewhat differently from other MTAs.

They reported these findings in Science Translational Medicine. The research was supported, in part, by Diazon Pharmaceuticals Inc.

The researchers tested DZ-2384 in mouse models of various cancers, including adult Philadelphia chromosome–negative acute lymphocytic leukemia.

In animals receiving DZ-2384, tumors shrank as much as or more than when a conventional MTA was used, but with much less toxicity at effective doses.

In particular, animals receiving DZ-2384 had markedly less peripheral neuropathy than those that received docetaxel, a conventional MTA. Peripheral neuropathy is one of the chief side effects of MTAs and can prompt treatment discontinuation.

“We have good reason to expect that human clinical trials of DZ-2384 will show that, at doses effective for treating a person’s cancer, there will be much less risk of the peripheral neuropathy that can force clinicians to stop treatment,” said study author Patrick Harran, PhD, of the University of California, Los Angeles.

Dr Harran believes clinical trials of DZ-2384 could begin within 2 years.

How this study began

Dr Harran began his work with diazonamides as a fundamental chemistry research problem.

In 1991, a group of researchers described diazonamides A and B, which they had isolated from the marine animal Diazona chinensis.

But Dr Harran and his colleagues found the described structure of diazonamide A was incorrect. In 2001, the team published a study that corrected the chemical structure of diazonamide A, and, 2 years later, they had synthesized the true structure in their lab.

Next, they began studying what the molecule might be doing to stop cells from dividing. In 2007, they discovered that the synthetic diazonamides they had produced minimized undesirable toxic effects that are commonly associated with chemotherapy.

Specifically, the compounds had an unusually large therapeutic window. In experiment after experiment, Dr Harran said, the researchers found that synthetic diazonamides’ therapeutic window was at least 10 times larger than that of traditional MTAs.

A key finding

In 2015, researchers prepared a form of DZ-2384 that was engineered with a molecular-scale “tracking device” so they could monitor its activity and better understand how it worked.

That helped the team confirm what they had come to suspect: that the compound binds to tubulin, which is a building block of mitotic spindles and a common target of MTAs.

Armed with this information, the researchers used X-ray crystallography to determine the structure of DZ-2384 bound to tubulin.

Their work offers a possible explanation for how DZ-2384 could disrupt dynamic tubulin polymers during cell division but spare those polymers in resting cells like neurons in the peripheral nervous system.

And that is what appears to allow the compound to attack growing cancer cells while minimizing damage to healthy cells.

Study authors Hui Ding

and Patrick Harran with

a model of DZ-2384

Photo courtesy of

Reed Hutchinson/UCLA

A new compound holds promise for treating leukemia and other cancers, according to researchers.

The compound, DZ-2384, is a synthetic version of diazonamide A, a toxin isolated from a marine animal.

DZ-2384 is a microtubule-targeting agent (MTA). It binds to and alters the stability of microtubules, disrupting the normal function of the mitotic spindle and arresting cell-cycle progression at mitosis, ultimately leading to cell death.

However, researchers found that DZ-2384 behaves somewhat differently from other MTAs.

They reported these findings in Science Translational Medicine. The research was supported, in part, by Diazon Pharmaceuticals Inc.

The researchers tested DZ-2384 in mouse models of various cancers, including adult Philadelphia chromosome–negative acute lymphocytic leukemia.

In animals receiving DZ-2384, tumors shrank as much as or more than when a conventional MTA was used, but with much less toxicity at effective doses.

In particular, animals receiving DZ-2384 had markedly less peripheral neuropathy than those that received docetaxel, a conventional MTA. Peripheral neuropathy is one of the chief side effects of MTAs and can prompt treatment discontinuation.

“We have good reason to expect that human clinical trials of DZ-2384 will show that, at doses effective for treating a person’s cancer, there will be much less risk of the peripheral neuropathy that can force clinicians to stop treatment,” said study author Patrick Harran, PhD, of the University of California, Los Angeles.

Dr Harran believes clinical trials of DZ-2384 could begin within 2 years.

How this study began

Dr Harran began his work with diazonamides as a fundamental chemistry research problem.

In 1991, a group of researchers described diazonamides A and B, which they had isolated from the marine animal Diazona chinensis.

But Dr Harran and his colleagues found the described structure of diazonamide A was incorrect. In 2001, the team published a study that corrected the chemical structure of diazonamide A, and, 2 years later, they had synthesized the true structure in their lab.

Next, they began studying what the molecule might be doing to stop cells from dividing. In 2007, they discovered that the synthetic diazonamides they had produced minimized undesirable toxic effects that are commonly associated with chemotherapy.

Specifically, the compounds had an unusually large therapeutic window. In experiment after experiment, Dr Harran said, the researchers found that synthetic diazonamides’ therapeutic window was at least 10 times larger than that of traditional MTAs.

A key finding

In 2015, researchers prepared a form of DZ-2384 that was engineered with a molecular-scale “tracking device” so they could monitor its activity and better understand how it worked.

That helped the team confirm what they had come to suspect: that the compound binds to tubulin, which is a building block of mitotic spindles and a common target of MTAs.

Armed with this information, the researchers used X-ray crystallography to determine the structure of DZ-2384 bound to tubulin.

Their work offers a possible explanation for how DZ-2384 could disrupt dynamic tubulin polymers during cell division but spare those polymers in resting cells like neurons in the peripheral nervous system.

And that is what appears to allow the compound to attack growing cancer cells while minimizing damage to healthy cells.

Study authors Hui Ding

and Patrick Harran with

a model of DZ-2384

Photo courtesy of

Reed Hutchinson/UCLA

A new compound holds promise for treating leukemia and other cancers, according to researchers.

The compound, DZ-2384, is a synthetic version of diazonamide A, a toxin isolated from a marine animal.

DZ-2384 is a microtubule-targeting agent (MTA). It binds to and alters the stability of microtubules, disrupting the normal function of the mitotic spindle and arresting cell-cycle progression at mitosis, ultimately leading to cell death.

However, researchers found that DZ-2384 behaves somewhat differently from other MTAs.

They reported these findings in Science Translational Medicine. The research was supported, in part, by Diazon Pharmaceuticals Inc.

The researchers tested DZ-2384 in mouse models of various cancers, including adult Philadelphia chromosome–negative acute lymphocytic leukemia.

In animals receiving DZ-2384, tumors shrank as much as or more than when a conventional MTA was used, but with much less toxicity at effective doses.

In particular, animals receiving DZ-2384 had markedly less peripheral neuropathy than those that received docetaxel, a conventional MTA. Peripheral neuropathy is one of the chief side effects of MTAs and can prompt treatment discontinuation.

“We have good reason to expect that human clinical trials of DZ-2384 will show that, at doses effective for treating a person’s cancer, there will be much less risk of the peripheral neuropathy that can force clinicians to stop treatment,” said study author Patrick Harran, PhD, of the University of California, Los Angeles.

Dr Harran believes clinical trials of DZ-2384 could begin within 2 years.

How this study began

Dr Harran began his work with diazonamides as a fundamental chemistry research problem.

In 1991, a group of researchers described diazonamides A and B, which they had isolated from the marine animal Diazona chinensis.

But Dr Harran and his colleagues found the described structure of diazonamide A was incorrect. In 2001, the team published a study that corrected the chemical structure of diazonamide A, and, 2 years later, they had synthesized the true structure in their lab.

Next, they began studying what the molecule might be doing to stop cells from dividing. In 2007, they discovered that the synthetic diazonamides they had produced minimized undesirable toxic effects that are commonly associated with chemotherapy.

Specifically, the compounds had an unusually large therapeutic window. In experiment after experiment, Dr Harran said, the researchers found that synthetic diazonamides’ therapeutic window was at least 10 times larger than that of traditional MTAs.

A key finding

In 2015, researchers prepared a form of DZ-2384 that was engineered with a molecular-scale “tracking device” so they could monitor its activity and better understand how it worked.

That helped the team confirm what they had come to suspect: that the compound binds to tubulin, which is a building block of mitotic spindles and a common target of MTAs.

Armed with this information, the researchers used X-ray crystallography to determine the structure of DZ-2384 bound to tubulin.

Their work offers a possible explanation for how DZ-2384 could disrupt dynamic tubulin polymers during cell division but spare those polymers in resting cells like neurons in the peripheral nervous system.

And that is what appears to allow the compound to attack growing cancer cells while minimizing damage to healthy cells.

Bivalirudin

Photo from Business Wire

NEW ORLEANS—Two types of anticoagulant therapy produce comparable outcomes for patients undergoing percutaneous coronary intervention (PCI), according to a new study.

The study was designed to determine which of 2 treatment methods—heparin combined with a short-term (less than 6 hours) infusion of tirofiban, or short-term periprocedural bivalirudin—was more effective.

Results showed that the 1-year risk of death, myocardial infarction, and urgent target vessel revascularization (UTVR) was not significantly different between the 2 treatment methods.

The incidence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding at 30 days was also similar between the treatment groups.

Results of this study were presented at the American Heart Association Scientific Sessions (abstract 15074). The study was funded by an unrestricted grant from the Medicure Corporation.

“Bivalirudin has been considered the gold standard for reducing bleeding during percutaneous coronary intervention, but our study shows heparin plus short-term tirofiban is just as good and possibly better,” said study investigator J. Brent Muhlestein, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.

“The results certainly justify a randomized clinical trial to explore identified trends.”

Dr Muhlestein and his colleagues studied data on patients who underwent PCI between January 2013 and December 2015.

Of the 857 patients enrolled in the study, 402 received heparin plus short-term tirofiban treatment, and 455 received bivalirudin. The patients were between the ages of 51 and 78.

Results

At 30 days, the incidence of TIMI major bleeding was 1.2% for patients treated with heparin and tirofiban and 3.1% for bivalirudin-treated patients (P=0.10).

Also at 30 days, the incidence of death was 0.7% in the heparin/tirofiban group and 1.9% in the bivalirudin group (P=0.23). The incidence of myocardial infarction was 0.5% and 0.7%, respectively (P=1.00). And the incidence of UTVR was 0% and 0.7%, respectively (P=0.25).

At 1 year, the incidence of death was 3.4% for patients treated with heparin and tirofiban and 5.5% for bivalirudin-treated patients (P=0.42).

The incidence of myocardial infarction at 1 year was 2.9% and 3.0%, respectively (P=1.00). And the incidence of UTVR was 2.0% and 1.5%, respectively (P=0.67).

In multivariable analysis, the odds ratio (OR) for 30-day TIMI major bleeding (heparin/tirofiban vs bivalirudin) was 0.41 (P=0.11).

The OR for death at 1 year was 0.50 (P=0.33). The OR for non-fatal myocardial infarction at 1 year was 1.09 (P=0.91). And the OR for UTVR at 1 year was 1.23 (P=0.84).

Bivalirudin

Photo from Business Wire

NEW ORLEANS—Two types of anticoagulant therapy produce comparable outcomes for patients undergoing percutaneous coronary intervention (PCI), according to a new study.

The study was designed to determine which of 2 treatment methods—heparin combined with a short-term (less than 6 hours) infusion of tirofiban, or short-term periprocedural bivalirudin—was more effective.

Results showed that the 1-year risk of death, myocardial infarction, and urgent target vessel revascularization (UTVR) was not significantly different between the 2 treatment methods.

The incidence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding at 30 days was also similar between the treatment groups.

Results of this study were presented at the American Heart Association Scientific Sessions (abstract 15074). The study was funded by an unrestricted grant from the Medicure Corporation.

“Bivalirudin has been considered the gold standard for reducing bleeding during percutaneous coronary intervention, but our study shows heparin plus short-term tirofiban is just as good and possibly better,” said study investigator J. Brent Muhlestein, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.

“The results certainly justify a randomized clinical trial to explore identified trends.”

Dr Muhlestein and his colleagues studied data on patients who underwent PCI between January 2013 and December 2015.

Of the 857 patients enrolled in the study, 402 received heparin plus short-term tirofiban treatment, and 455 received bivalirudin. The patients were between the ages of 51 and 78.

Results

At 30 days, the incidence of TIMI major bleeding was 1.2% for patients treated with heparin and tirofiban and 3.1% for bivalirudin-treated patients (P=0.10).

Also at 30 days, the incidence of death was 0.7% in the heparin/tirofiban group and 1.9% in the bivalirudin group (P=0.23). The incidence of myocardial infarction was 0.5% and 0.7%, respectively (P=1.00). And the incidence of UTVR was 0% and 0.7%, respectively (P=0.25).

At 1 year, the incidence of death was 3.4% for patients treated with heparin and tirofiban and 5.5% for bivalirudin-treated patients (P=0.42).

The incidence of myocardial infarction at 1 year was 2.9% and 3.0%, respectively (P=1.00). And the incidence of UTVR was 2.0% and 1.5%, respectively (P=0.67).

In multivariable analysis, the odds ratio (OR) for 30-day TIMI major bleeding (heparin/tirofiban vs bivalirudin) was 0.41 (P=0.11).

The OR for death at 1 year was 0.50 (P=0.33). The OR for non-fatal myocardial infarction at 1 year was 1.09 (P=0.91). And the OR for UTVR at 1 year was 1.23 (P=0.84).

Bivalirudin

Photo from Business Wire

NEW ORLEANS—Two types of anticoagulant therapy produce comparable outcomes for patients undergoing percutaneous coronary intervention (PCI), according to a new study.

The study was designed to determine which of 2 treatment methods—heparin combined with a short-term (less than 6 hours) infusion of tirofiban, or short-term periprocedural bivalirudin—was more effective.

Results showed that the 1-year risk of death, myocardial infarction, and urgent target vessel revascularization (UTVR) was not significantly different between the 2 treatment methods.

The incidence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding at 30 days was also similar between the treatment groups.

Results of this study were presented at the American Heart Association Scientific Sessions (abstract 15074). The study was funded by an unrestricted grant from the Medicure Corporation.

“Bivalirudin has been considered the gold standard for reducing bleeding during percutaneous coronary intervention, but our study shows heparin plus short-term tirofiban is just as good and possibly better,” said study investigator J. Brent Muhlestein, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.

“The results certainly justify a randomized clinical trial to explore identified trends.”

Dr Muhlestein and his colleagues studied data on patients who underwent PCI between January 2013 and December 2015.

Of the 857 patients enrolled in the study, 402 received heparin plus short-term tirofiban treatment, and 455 received bivalirudin. The patients were between the ages of 51 and 78.

Results

At 30 days, the incidence of TIMI major bleeding was 1.2% for patients treated with heparin and tirofiban and 3.1% for bivalirudin-treated patients (P=0.10).

Also at 30 days, the incidence of death was 0.7% in the heparin/tirofiban group and 1.9% in the bivalirudin group (P=0.23). The incidence of myocardial infarction was 0.5% and 0.7%, respectively (P=1.00). And the incidence of UTVR was 0% and 0.7%, respectively (P=0.25).

At 1 year, the incidence of death was 3.4% for patients treated with heparin and tirofiban and 5.5% for bivalirudin-treated patients (P=0.42).

The incidence of myocardial infarction at 1 year was 2.9% and 3.0%, respectively (P=1.00). And the incidence of UTVR was 2.0% and 1.5%, respectively (P=0.67).

In multivariable analysis, the odds ratio (OR) for 30-day TIMI major bleeding (heparin/tirofiban vs bivalirudin) was 0.41 (P=0.11).

The OR for death at 1 year was 0.50 (P=0.33). The OR for non-fatal myocardial infarction at 1 year was 1.09 (P=0.91). And the OR for UTVR at 1 year was 1.23 (P=0.84).

Smiling baby

Photo by Petr Kratochvil

After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic

leukemia (ALL).

The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.

This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).

“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.

“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”

That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.

However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.

The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.

“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”

That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.

So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.

The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.

The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.

Smiling baby

Photo by Petr Kratochvil

After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic

leukemia (ALL).

The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.

This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).

“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.

“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”

That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.

However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.

The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.

“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”

That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.

So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.

The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.

The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.

Smiling baby

Photo by Petr Kratochvil

After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic

leukemia (ALL).

The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.

This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).

“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.

“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”

That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.

However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.

The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.

“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”

That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.

So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.

The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.

The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.

Rivaroxaban

NEW ORLEANS—Results of the PIONEER AF-PCI trial suggest certain patients may have a lower risk of bleeding if they receive rivaroxaban rather than a vitamin K antagonist (VKA).

The study showed that patients with nonvalvular atrial fibrillation (NVAF) who underwent percutaneous coronary intervention (PCI) with stenting had a lower risk of clinically significant bleeding if they received rivaroxaban plus antiplatelet therapy rather than a VKA plus antiplatelet therapy.

However, the trial showed no significant difference between the treatment groups when it came to the risk of cardiovascular events.

These results were presented at the American Heart Association’s Scientific Sessions 2016 and simultaneously published in NEJM.

The trial was supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals.

“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” said study investigator C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.

“This trial, which tested 2 entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with antiplatelet therapy is successful in minimizing bleeding while preventing clotting.”

The trial included 2124 patients with NVAF who had undergone PCI with stenting. They were randomized to receive, in a 1:1:1 ratio:

• Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1)
• Very-low-dose rivaroxaban (2.5 mg twice daily) plus dual antiplatelet therapy (DAPT) for 1, 6, or 12 months (group 2)
• Standard therapy with a dose-adjusted VKA (once daily) plus DAPT for 1, 6, or 12 months (group 3).

Key endpoints

The study’s primary safety endpoint was clinically significant bleeding, which was a composite of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria, minor bleeding according to TIMI criteria, and bleeding requiring medical attention.

At 1 year, the rate of clinically significant bleeding was significantly lower in the 2 rivaroxaban groups than in the VKA group—16.8% in group 1, 18.0% in group 2, and 26.7% in group 3.

The hazard ratio for group 1 compared to group 3 was 0.59 (P<0.001). And the hazard ratio for group 2 compared to group 3 was 0.63 (P<0.001).

The researchers said this reduction in bleeding for the 2 rivaroxaban groups was consistent across multiple subgroups of patients.

The study’s key efficacy endpoint was major adverse cardiovascular events, which was a composite of death from cardiovascular causes, myocardial infarction, and stroke.

There was no significant difference between the groups with regard to this endpoint. It occurred in 6.5% of the patients in group 1, 5.6% in group 2, and 6.0% in group 3 (P>0.05 for both comparisons).

“For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care,” Dr Gibson said.

“Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study, with significantly less bleeding and numerically similar efficacy when compared to warfarin [VKA] with dual antiplatelet therapy.”

Rivaroxaban

NEW ORLEANS—Results of the PIONEER AF-PCI trial suggest certain patients may have a lower risk of bleeding if they receive rivaroxaban rather than a vitamin K antagonist (VKA).

The study showed that patients with nonvalvular atrial fibrillation (NVAF) who underwent percutaneous coronary intervention (PCI) with stenting had a lower risk of clinically significant bleeding if they received rivaroxaban plus antiplatelet therapy rather than a VKA plus antiplatelet therapy.

However, the trial showed no significant difference between the treatment groups when it came to the risk of cardiovascular events.

These results were presented at the American Heart Association’s Scientific Sessions 2016 and simultaneously published in NEJM.

The trial was supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals.

“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” said study investigator C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.

“This trial, which tested 2 entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with antiplatelet therapy is successful in minimizing bleeding while preventing clotting.”

The trial included 2124 patients with NVAF who had undergone PCI with stenting. They were randomized to receive, in a 1:1:1 ratio:

• Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1)
• Very-low-dose rivaroxaban (2.5 mg twice daily) plus dual antiplatelet therapy (DAPT) for 1, 6, or 12 months (group 2)
• Standard therapy with a dose-adjusted VKA (once daily) plus DAPT for 1, 6, or 12 months (group 3).

Key endpoints

The study’s primary safety endpoint was clinically significant bleeding, which was a composite of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria, minor bleeding according to TIMI criteria, and bleeding requiring medical attention.

At 1 year, the rate of clinically significant bleeding was significantly lower in the 2 rivaroxaban groups than in the VKA group—16.8% in group 1, 18.0% in group 2, and 26.7% in group 3.

The hazard ratio for group 1 compared to group 3 was 0.59 (P<0.001). And the hazard ratio for group 2 compared to group 3 was 0.63 (P<0.001).

The researchers said this reduction in bleeding for the 2 rivaroxaban groups was consistent across multiple subgroups of patients.

The study’s key efficacy endpoint was major adverse cardiovascular events, which was a composite of death from cardiovascular causes, myocardial infarction, and stroke.

There was no significant difference between the groups with regard to this endpoint. It occurred in 6.5% of the patients in group 1, 5.6% in group 2, and 6.0% in group 3 (P>0.05 for both comparisons).

“For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care,” Dr Gibson said.

“Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study, with significantly less bleeding and numerically similar efficacy when compared to warfarin [VKA] with dual antiplatelet therapy.”

Rivaroxaban

NEW ORLEANS—Results of the PIONEER AF-PCI trial suggest certain patients may have a lower risk of bleeding if they receive rivaroxaban rather than a vitamin K antagonist (VKA).

The study showed that patients with nonvalvular atrial fibrillation (NVAF) who underwent percutaneous coronary intervention (PCI) with stenting had a lower risk of clinically significant bleeding if they received rivaroxaban plus antiplatelet therapy rather than a VKA plus antiplatelet therapy.

However, the trial showed no significant difference between the treatment groups when it came to the risk of cardiovascular events.

These results were presented at the American Heart Association’s Scientific Sessions 2016 and simultaneously published in NEJM.

The trial was supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals.

“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” said study investigator C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.

“This trial, which tested 2 entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with antiplatelet therapy is successful in minimizing bleeding while preventing clotting.”

The trial included 2124 patients with NVAF who had undergone PCI with stenting. They were randomized to receive, in a 1:1:1 ratio:

• Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1)
• Very-low-dose rivaroxaban (2.5 mg twice daily) plus dual antiplatelet therapy (DAPT) for 1, 6, or 12 months (group 2)
• Standard therapy with a dose-adjusted VKA (once daily) plus DAPT for 1, 6, or 12 months (group 3).

Key endpoints

The study’s primary safety endpoint was clinically significant bleeding, which was a composite of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria, minor bleeding according to TIMI criteria, and bleeding requiring medical attention.

At 1 year, the rate of clinically significant bleeding was significantly lower in the 2 rivaroxaban groups than in the VKA group—16.8% in group 1, 18.0% in group 2, and 26.7% in group 3.

The hazard ratio for group 1 compared to group 3 was 0.59 (P<0.001). And the hazard ratio for group 2 compared to group 3 was 0.63 (P<0.001).

The researchers said this reduction in bleeding for the 2 rivaroxaban groups was consistent across multiple subgroups of patients.

The study’s key efficacy endpoint was major adverse cardiovascular events, which was a composite of death from cardiovascular causes, myocardial infarction, and stroke.

There was no significant difference between the groups with regard to this endpoint. It occurred in 6.5% of the patients in group 1, 5.6% in group 2, and 6.0% in group 3 (P>0.05 for both comparisons).

“For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care,” Dr Gibson said.

“Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study, with significantly less bleeding and numerically similar efficacy when compared to warfarin [VKA] with dual antiplatelet therapy.”