European Society of Cardiology (ESC): Annual Congress

Ticagrelor tablets

Photo courtesy of AstraZeneca

ROME—The antiplatelet drugs prasugrel and ticagrelor produce similar early results in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), according to PRAGUE-18, the first randomized, head-to-head comparison of the drugs.

“Our findings confirm previous indirect—non-randomized—comparisons of these 2 drugs, based on analyses of various registries,” said study investigator Petr Widimsky MD, DSc, of Charles University in Prague, Czech Republic.

“Thus, both drugs are very effective and safe and significantly contribute to the excellent outcomes of patients with acute myocardial infarction in modern cardiology.”

Dr Widimsky presented results from PRAGUE-18 at ESC Congress 2016 (abstract 5028). This was an investigator-initiated study, so there was no industry support.

The trial included 1230 AMI patients who were randomized to receive prasugrel (n=634) or ticagrelor (n=596) prior to PCI. There were no significant differences in baseline characteristics between the treatment arms.

Randomization took place immediately after a patient’s arrival to the PCI center. Patients received prasugrel at 60 mg, followed by 10 mg per day (5 mg per day if they were older than 75 or weighed less than 60 kg) for 1 year. Patients received ticagrelor at 180 mg, followed by 90 mg twice a day for 1 year.

The study’s primary endpoint was the occurrence of death, re-infarction, urgent target vessel revascularization, stroke, prolonged hospitalization, or serious bleeding requiring transfusion at 7 days (or discharge if earlier).

The trial was halted prematurely, after an interim analysis showed no significant difference in the rate of the primary endpoint between the prasugrel and ticagrelor arms—4.0% and 4.1%, respectively (odds ratio=0.98, P=0.939).

Likewise, there was no significant difference between the treatment arms for any of the components of the primary endpoint.

The key secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke within 30 days. There was no significant difference in the rate of this endpoint between the prasugrel and ticagrelor arms—2.7% and 2.5%, respectively (odds ratio=1.06, P=0.864).

“This study did not show any difference between ticagrelor and prasugrel in the early phase of acute myocardial infarction treated by primary PCI,” Dr Widimsky concluded.

He and his colleagues are planning the final follow-up of this study at 1 year, which will be completed in 2017.

Ticagrelor tablets

Photo courtesy of AstraZeneca

ROME—The antiplatelet drugs prasugrel and ticagrelor produce similar early results in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), according to PRAGUE-18, the first randomized, head-to-head comparison of the drugs.

“Our findings confirm previous indirect—non-randomized—comparisons of these 2 drugs, based on analyses of various registries,” said study investigator Petr Widimsky MD, DSc, of Charles University in Prague, Czech Republic.

“Thus, both drugs are very effective and safe and significantly contribute to the excellent outcomes of patients with acute myocardial infarction in modern cardiology.”

Dr Widimsky presented results from PRAGUE-18 at ESC Congress 2016 (abstract 5028). This was an investigator-initiated study, so there was no industry support.

The trial included 1230 AMI patients who were randomized to receive prasugrel (n=634) or ticagrelor (n=596) prior to PCI. There were no significant differences in baseline characteristics between the treatment arms.

Randomization took place immediately after a patient’s arrival to the PCI center. Patients received prasugrel at 60 mg, followed by 10 mg per day (5 mg per day if they were older than 75 or weighed less than 60 kg) for 1 year. Patients received ticagrelor at 180 mg, followed by 90 mg twice a day for 1 year.

The study’s primary endpoint was the occurrence of death, re-infarction, urgent target vessel revascularization, stroke, prolonged hospitalization, or serious bleeding requiring transfusion at 7 days (or discharge if earlier).

The trial was halted prematurely, after an interim analysis showed no significant difference in the rate of the primary endpoint between the prasugrel and ticagrelor arms—4.0% and 4.1%, respectively (odds ratio=0.98, P=0.939).

Likewise, there was no significant difference between the treatment arms for any of the components of the primary endpoint.

The key secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke within 30 days. There was no significant difference in the rate of this endpoint between the prasugrel and ticagrelor arms—2.7% and 2.5%, respectively (odds ratio=1.06, P=0.864).

“This study did not show any difference between ticagrelor and prasugrel in the early phase of acute myocardial infarction treated by primary PCI,” Dr Widimsky concluded.

He and his colleagues are planning the final follow-up of this study at 1 year, which will be completed in 2017.

Ticagrelor tablets

Photo courtesy of AstraZeneca

ROME—The antiplatelet drugs prasugrel and ticagrelor produce similar early results in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), according to PRAGUE-18, the first randomized, head-to-head comparison of the drugs.

“Our findings confirm previous indirect—non-randomized—comparisons of these 2 drugs, based on analyses of various registries,” said study investigator Petr Widimsky MD, DSc, of Charles University in Prague, Czech Republic.

“Thus, both drugs are very effective and safe and significantly contribute to the excellent outcomes of patients with acute myocardial infarction in modern cardiology.”

Dr Widimsky presented results from PRAGUE-18 at ESC Congress 2016 (abstract 5028). This was an investigator-initiated study, so there was no industry support.

The trial included 1230 AMI patients who were randomized to receive prasugrel (n=634) or ticagrelor (n=596) prior to PCI. There were no significant differences in baseline characteristics between the treatment arms.

Randomization took place immediately after a patient’s arrival to the PCI center. Patients received prasugrel at 60 mg, followed by 10 mg per day (5 mg per day if they were older than 75 or weighed less than 60 kg) for 1 year. Patients received ticagrelor at 180 mg, followed by 90 mg twice a day for 1 year.

The study’s primary endpoint was the occurrence of death, re-infarction, urgent target vessel revascularization, stroke, prolonged hospitalization, or serious bleeding requiring transfusion at 7 days (or discharge if earlier).

The trial was halted prematurely, after an interim analysis showed no significant difference in the rate of the primary endpoint between the prasugrel and ticagrelor arms—4.0% and 4.1%, respectively (odds ratio=0.98, P=0.939).

Likewise, there was no significant difference between the treatment arms for any of the components of the primary endpoint.

The key secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke within 30 days. There was no significant difference in the rate of this endpoint between the prasugrel and ticagrelor arms—2.7% and 2.5%, respectively (odds ratio=1.06, P=0.864).

“This study did not show any difference between ticagrelor and prasugrel in the early phase of acute myocardial infarction treated by primary PCI,” Dr Widimsky concluded.

He and his colleagues are planning the final follow-up of this study at 1 year, which will be completed in 2017.

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

bjancin@frontlinemedcom.com

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

bjancin@frontlinemedcom.com

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

bjancin@frontlinemedcom.com

Three generations

of women in a family

ROME—According to researchers, a clinical decision rule can identify women who, after their first unprovoked venous thromboembolism (VTE), have a low risk of VTE recurrence and might safely discontinue anticoagulant therapy.

The researchers evaluated the HERDOO2 rule, which is named after the risk factors the rule employs to determine the likelihood of VTE recurrence, in the REVERSE II trial.

Results from the trial were presented at ESC Congress 2016 (abstract 5721).

According to the HERDOO2 rule, the following risk factors must be considered to determine a patient’s risk of VTE recurrence:

1. Hyperpigmentation, Edema, or Redness in either leg
2. D-dimer >250 μg/mL on anticoagulants
3. Obesity with body mass index >30 kg/m²
4. Older than age 65.

Women (but not men) are considered at low risk of VTE recurrence if they have 0 to 1 of these risk factors.

In the REVERSE II trial, researchers tested the HERDOO2 rule in 2779 male and female patients with a first unprovoked VTE who had completed 5 to 12 months of anticoagulant therapy.

After drop-outs and exclusions, 622 women were considered low-risk, based on HERDOO2 criteria, and the majority of these women (n=591) discontinued anticoagulant therapy.

Thirty-one low-risk women continued anticoagulant therapy, as did 1802 men and high-risk women (with 2 or more HERDOO2 criteria). Three hundred and twenty-three men and high-risk women discontinued anticoagulant therapy.

After a year of follow-up, low-risk women who had discontinued anticoagulants had a 3% rate of recurrent VTE per patient year, and low-risk women who continued anticoagulant therapy had no VTEs.

Among the men and high-risk women, the rate of recurrent VTE per patient year was 8.1% in patients who discontinued therapy and 1.6% in patients who continued to receive anticoagulant therapy.

“This is an important finding as, using our rule, over half of women with unprovoked VTE can safely discontinue anticoagulants and be spared the burdens, costs, and risks of life-long anticoagulation,” said study investigator Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.

“Since current consensus guidelines suggest anticoagulants should be continued indefinitely in all patients with unprovoked VTE and non-high bleeding risk, our results are potentially practice-changing.”

Dr Rodger noted, however, that questions remain regarding anticoagulation duration after a first unprovoked VTE.

“One is whether indefinite anticoagulation is required for men and high-risk women, [which] was not the primary focus of our study,” he said. “The second is in the subgroup of post-menopausal women aged 50 and above.”

“In this group, even those who were considered low-risk according to the HERDOO2 rule had a higher than expected rate of recurrent VTE (5.7%) when they discontinued anticoagulants. As such, further validation of HERDOO2 is required in this subset of post-menopausal women.”

Three generations

of women in a family

ROME—According to researchers, a clinical decision rule can identify women who, after their first unprovoked venous thromboembolism (VTE), have a low risk of VTE recurrence and might safely discontinue anticoagulant therapy.

The researchers evaluated the HERDOO2 rule, which is named after the risk factors the rule employs to determine the likelihood of VTE recurrence, in the REVERSE II trial.

Results from the trial were presented at ESC Congress 2016 (abstract 5721).

According to the HERDOO2 rule, the following risk factors must be considered to determine a patient’s risk of VTE recurrence:

1. Hyperpigmentation, Edema, or Redness in either leg
2. D-dimer >250 μg/mL on anticoagulants
3. Obesity with body mass index >30 kg/m²
4. Older than age 65.

Women (but not men) are considered at low risk of VTE recurrence if they have 0 to 1 of these risk factors.

In the REVERSE II trial, researchers tested the HERDOO2 rule in 2779 male and female patients with a first unprovoked VTE who had completed 5 to 12 months of anticoagulant therapy.

After drop-outs and exclusions, 622 women were considered low-risk, based on HERDOO2 criteria, and the majority of these women (n=591) discontinued anticoagulant therapy.

Thirty-one low-risk women continued anticoagulant therapy, as did 1802 men and high-risk women (with 2 or more HERDOO2 criteria). Three hundred and twenty-three men and high-risk women discontinued anticoagulant therapy.

After a year of follow-up, low-risk women who had discontinued anticoagulants had a 3% rate of recurrent VTE per patient year, and low-risk women who continued anticoagulant therapy had no VTEs.

Among the men and high-risk women, the rate of recurrent VTE per patient year was 8.1% in patients who discontinued therapy and 1.6% in patients who continued to receive anticoagulant therapy.

“This is an important finding as, using our rule, over half of women with unprovoked VTE can safely discontinue anticoagulants and be spared the burdens, costs, and risks of life-long anticoagulation,” said study investigator Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.

“Since current consensus guidelines suggest anticoagulants should be continued indefinitely in all patients with unprovoked VTE and non-high bleeding risk, our results are potentially practice-changing.”

Dr Rodger noted, however, that questions remain regarding anticoagulation duration after a first unprovoked VTE.

“One is whether indefinite anticoagulation is required for men and high-risk women, [which] was not the primary focus of our study,” he said. “The second is in the subgroup of post-menopausal women aged 50 and above.”

“In this group, even those who were considered low-risk according to the HERDOO2 rule had a higher than expected rate of recurrent VTE (5.7%) when they discontinued anticoagulants. As such, further validation of HERDOO2 is required in this subset of post-menopausal women.”

Three generations

of women in a family

ROME—According to researchers, a clinical decision rule can identify women who, after their first unprovoked venous thromboembolism (VTE), have a low risk of VTE recurrence and might safely discontinue anticoagulant therapy.

The researchers evaluated the HERDOO2 rule, which is named after the risk factors the rule employs to determine the likelihood of VTE recurrence, in the REVERSE II trial.

Results from the trial were presented at ESC Congress 2016 (abstract 5721).

According to the HERDOO2 rule, the following risk factors must be considered to determine a patient’s risk of VTE recurrence:

1. Hyperpigmentation, Edema, or Redness in either leg
2. D-dimer >250 μg/mL on anticoagulants
3. Obesity with body mass index >30 kg/m²
4. Older than age 65.

Women (but not men) are considered at low risk of VTE recurrence if they have 0 to 1 of these risk factors.

In the REVERSE II trial, researchers tested the HERDOO2 rule in 2779 male and female patients with a first unprovoked VTE who had completed 5 to 12 months of anticoagulant therapy.

After drop-outs and exclusions, 622 women were considered low-risk, based on HERDOO2 criteria, and the majority of these women (n=591) discontinued anticoagulant therapy.

Thirty-one low-risk women continued anticoagulant therapy, as did 1802 men and high-risk women (with 2 or more HERDOO2 criteria). Three hundred and twenty-three men and high-risk women discontinued anticoagulant therapy.

After a year of follow-up, low-risk women who had discontinued anticoagulants had a 3% rate of recurrent VTE per patient year, and low-risk women who continued anticoagulant therapy had no VTEs.

Among the men and high-risk women, the rate of recurrent VTE per patient year was 8.1% in patients who discontinued therapy and 1.6% in patients who continued to receive anticoagulant therapy.

“This is an important finding as, using our rule, over half of women with unprovoked VTE can safely discontinue anticoagulants and be spared the burdens, costs, and risks of life-long anticoagulation,” said study investigator Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.

“Since current consensus guidelines suggest anticoagulants should be continued indefinitely in all patients with unprovoked VTE and non-high bleeding risk, our results are potentially practice-changing.”

Dr Rodger noted, however, that questions remain regarding anticoagulation duration after a first unprovoked VTE.

“One is whether indefinite anticoagulation is required for men and high-risk women, [which] was not the primary focus of our study,” he said. “The second is in the subgroup of post-menopausal women aged 50 and above.”

“In this group, even those who were considered low-risk according to the HERDOO2 rule had a higher than expected rate of recurrent VTE (5.7%) when they discontinued anticoagulants. As such, further validation of HERDOO2 is required in this subset of post-menopausal women.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.

Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.

Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).

“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.

The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.

MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.

“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.

CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.

Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.

His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.

Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.

Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).

“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.

The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.

MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.

“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.

CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.

Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.

His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.

Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.

Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).

“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.

The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.

MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.

“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.

CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.

Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.

His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Weekly lipoprotein apheresis in patients with highly refractory angina accompanied by high plasma lipoprotein(a) without elevated LDL cholesterol led to significantly improved myocardial blood flow in a randomized, blinded, sham-controlled clinical trial, Tina Khan, MD, reported at the annual congress of the European Society of Cardiology.

Participants also experienced clinically meaningful improvements in the secondary endpoints of quality of life, angina symptoms, exercise capacity, and atheroma burden, added Dr. Khan of Imperial College London.

Bruce Jancin/Frontline Medical News

Angina pectoris that is refractory to maximal pharmacologic, percutaneous, and surgical interventions is a major and growing problem. More than 100,000 new cases occur per year in the United States.

“We have a desperate need to develop new therapeutic options,” she said.

Lipoprotein(a), or Lp(a), is a potent independent cardiovascular risk factor. And it figures prominently in refractory angina. Indeed, 60% of the patients with refractory angina screened by Dr. Khan for her clinical trial had an isolated plasma Lp(a) level of 50 mg/dL or more, the threshold at which cardiovascular risk sharply increases. Statins have no effect on Lp(a) levels.

While a couple of observational cohort studies have suggested that reducing elevated Lp(a) in patients with cardiovascular disease is associated with a decrease in major adverse cardiovascular events, until now there have been no randomized controlled trials of apheresis as Lp(a)-lowering therapy in patients with refractory angina, according to Dr. Khan.

She presented a randomized, crossover design study in 20 patients with severe refractory angina and an Lp(a) in excess of 50 mg/dL but no elevation in LDL. They underwent 3 months of blinded weekly extracorporeal lipoprotein apheresis using a dextran sulfate filtration system or sham apheresis, followed by a month-long washout period. Participants were then crossed over to the other study arm to increase the statistical power of this small study.

The primary study endpoint was change in myocardial perfusion reserve as measured by cardiovascular magnetic resonance imaging at baseline and after 3 months of true or sham apheresis. The myocardial perfusion reserve index improved by a net of 0.63 after apheresis from a baseline of 1.45. This effect was strongly driven by a substantial increase in stress myocardial perfusion, with very little change in perfusion at rest.

Significant improvements were also recorded after apheresis in the secondary endpoints of change in carotid atheroma as reflected in total carotid wall volume, improvement on various domains of the Seattle Angina Questionnaire, physical limitations as scored on the SF-36, and exercise capacity as measured on the 6-minute walk test.

Discussant Peter Libby, MD, was effusive in his praise for Dr. Khan’s study.

Bruce Jancin/Frontline Medical News

“This is a wonderful example of how we may be able to offer new hope for patients and families with high Lp(a),” declared Dr. Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

He approved of the methodology and embraced what he called “the intriguing preliminary picture of benefit for lowering Lp(a).”

Most of all, he was pleased that Dr. Khan’s well conducted albeit small study has thrown a spotlight on Lp(a), which he characterized as a greatly underappreciated causal risk factor for a range of cardiovascular diseases.

“Lp(a) stands out like a Manhattan skyscraper as the major driver of calcific aortic stenosis, an epidemic that we see in our aging population,” he observed.

He added that topics worthy of further research with regard to Lp(a)-lowering apheresis as a treatment for refractory angina include the question of whether the mechanism of benefit involves structural changes in atherosclerosis or functional changes. And if it’s the latter, is it a matter of changes in microvascular function, macrovascular function, or a combination of the two?

Apheresis is extremely costly, inconvenient, and invasive, and there are only several dozen apheresis centers in the United States. So the future of Lp(a)-lowering to treat refractory angina, calcific aortic stenosis, and other cardiovascular conditions where elevated Lp(a) is an important player may lie in pharmacotherapy with the PCSK9 inhibitors, Dr. Libby predicted.

He cited “very promising” data showing that evolocumab (Repatha) and alirocumab (Praluent) lower Lp(a) in dose-dependent fashion. Ongoing very large clinical trials with hard clinical endpoints should eventually provide key information regarding the cardiovascular benefits of lowering Lp(a).

“We may be entering an era where we may be able to offer our patients and families – because this is often a familial problem – a non-apheresis approach to controlling what we are learning is a very important causal risk factor for atherosclerosis,” Dr. Libby said.

Patrick M. Moriarty, MD, said in a video interview that he was very intrigued by the results, and “not personally surprised.” They should stimulate interest in cardiologists to start measuring Lp(a) in their patients like those in this study, in whom the disease severity doesn’t match up with the clinical risk factors, said Dr. Moriarty of the University of Kansas, Kansas City.

Dr. Khan’s study was funded by the UK National Institute for Health Research. She reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ROME – Weekly lipoprotein apheresis in patients with highly refractory angina accompanied by high plasma lipoprotein(a) without elevated LDL cholesterol led to significantly improved myocardial blood flow in a randomized, blinded, sham-controlled clinical trial, Tina Khan, MD, reported at the annual congress of the European Society of Cardiology.

Participants also experienced clinically meaningful improvements in the secondary endpoints of quality of life, angina symptoms, exercise capacity, and atheroma burden, added Dr. Khan of Imperial College London.

Bruce Jancin/Frontline Medical News

Angina pectoris that is refractory to maximal pharmacologic, percutaneous, and surgical interventions is a major and growing problem. More than 100,000 new cases occur per year in the United States.

“We have a desperate need to develop new therapeutic options,” she said.

Lipoprotein(a), or Lp(a), is a potent independent cardiovascular risk factor. And it figures prominently in refractory angina. Indeed, 60% of the patients with refractory angina screened by Dr. Khan for her clinical trial had an isolated plasma Lp(a) level of 50 mg/dL or more, the threshold at which cardiovascular risk sharply increases. Statins have no effect on Lp(a) levels.

While a couple of observational cohort studies have suggested that reducing elevated Lp(a) in patients with cardiovascular disease is associated with a decrease in major adverse cardiovascular events, until now there have been no randomized controlled trials of apheresis as Lp(a)-lowering therapy in patients with refractory angina, according to Dr. Khan.

She presented a randomized, crossover design study in 20 patients with severe refractory angina and an Lp(a) in excess of 50 mg/dL but no elevation in LDL. They underwent 3 months of blinded weekly extracorporeal lipoprotein apheresis using a dextran sulfate filtration system or sham apheresis, followed by a month-long washout period. Participants were then crossed over to the other study arm to increase the statistical power of this small study.

The primary study endpoint was change in myocardial perfusion reserve as measured by cardiovascular magnetic resonance imaging at baseline and after 3 months of true or sham apheresis. The myocardial perfusion reserve index improved by a net of 0.63 after apheresis from a baseline of 1.45. This effect was strongly driven by a substantial increase in stress myocardial perfusion, with very little change in perfusion at rest.

Significant improvements were also recorded after apheresis in the secondary endpoints of change in carotid atheroma as reflected in total carotid wall volume, improvement on various domains of the Seattle Angina Questionnaire, physical limitations as scored on the SF-36, and exercise capacity as measured on the 6-minute walk test.

Discussant Peter Libby, MD, was effusive in his praise for Dr. Khan’s study.

Bruce Jancin/Frontline Medical News

“This is a wonderful example of how we may be able to offer new hope for patients and families with high Lp(a),” declared Dr. Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

He approved of the methodology and embraced what he called “the intriguing preliminary picture of benefit for lowering Lp(a).”

Most of all, he was pleased that Dr. Khan’s well conducted albeit small study has thrown a spotlight on Lp(a), which he characterized as a greatly underappreciated causal risk factor for a range of cardiovascular diseases.

“Lp(a) stands out like a Manhattan skyscraper as the major driver of calcific aortic stenosis, an epidemic that we see in our aging population,” he observed.

He added that topics worthy of further research with regard to Lp(a)-lowering apheresis as a treatment for refractory angina include the question of whether the mechanism of benefit involves structural changes in atherosclerosis or functional changes. And if it’s the latter, is it a matter of changes in microvascular function, macrovascular function, or a combination of the two?

Apheresis is extremely costly, inconvenient, and invasive, and there are only several dozen apheresis centers in the United States. So the future of Lp(a)-lowering to treat refractory angina, calcific aortic stenosis, and other cardiovascular conditions where elevated Lp(a) is an important player may lie in pharmacotherapy with the PCSK9 inhibitors, Dr. Libby predicted.

He cited “very promising” data showing that evolocumab (Repatha) and alirocumab (Praluent) lower Lp(a) in dose-dependent fashion. Ongoing very large clinical trials with hard clinical endpoints should eventually provide key information regarding the cardiovascular benefits of lowering Lp(a).

“We may be entering an era where we may be able to offer our patients and families – because this is often a familial problem – a non-apheresis approach to controlling what we are learning is a very important causal risk factor for atherosclerosis,” Dr. Libby said.

Patrick M. Moriarty, MD, said in a video interview that he was very intrigued by the results, and “not personally surprised.” They should stimulate interest in cardiologists to start measuring Lp(a) in their patients like those in this study, in whom the disease severity doesn’t match up with the clinical risk factors, said Dr. Moriarty of the University of Kansas, Kansas City.

Dr. Khan’s study was funded by the UK National Institute for Health Research. She reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ROME – Weekly lipoprotein apheresis in patients with highly refractory angina accompanied by high plasma lipoprotein(a) without elevated LDL cholesterol led to significantly improved myocardial blood flow in a randomized, blinded, sham-controlled clinical trial, Tina Khan, MD, reported at the annual congress of the European Society of Cardiology.

Participants also experienced clinically meaningful improvements in the secondary endpoints of quality of life, angina symptoms, exercise capacity, and atheroma burden, added Dr. Khan of Imperial College London.

Bruce Jancin/Frontline Medical News

Angina pectoris that is refractory to maximal pharmacologic, percutaneous, and surgical interventions is a major and growing problem. More than 100,000 new cases occur per year in the United States.

“We have a desperate need to develop new therapeutic options,” she said.

Lipoprotein(a), or Lp(a), is a potent independent cardiovascular risk factor. And it figures prominently in refractory angina. Indeed, 60% of the patients with refractory angina screened by Dr. Khan for her clinical trial had an isolated plasma Lp(a) level of 50 mg/dL or more, the threshold at which cardiovascular risk sharply increases. Statins have no effect on Lp(a) levels.

While a couple of observational cohort studies have suggested that reducing elevated Lp(a) in patients with cardiovascular disease is associated with a decrease in major adverse cardiovascular events, until now there have been no randomized controlled trials of apheresis as Lp(a)-lowering therapy in patients with refractory angina, according to Dr. Khan.

She presented a randomized, crossover design study in 20 patients with severe refractory angina and an Lp(a) in excess of 50 mg/dL but no elevation in LDL. They underwent 3 months of blinded weekly extracorporeal lipoprotein apheresis using a dextran sulfate filtration system or sham apheresis, followed by a month-long washout period. Participants were then crossed over to the other study arm to increase the statistical power of this small study.

The primary study endpoint was change in myocardial perfusion reserve as measured by cardiovascular magnetic resonance imaging at baseline and after 3 months of true or sham apheresis. The myocardial perfusion reserve index improved by a net of 0.63 after apheresis from a baseline of 1.45. This effect was strongly driven by a substantial increase in stress myocardial perfusion, with very little change in perfusion at rest.

Significant improvements were also recorded after apheresis in the secondary endpoints of change in carotid atheroma as reflected in total carotid wall volume, improvement on various domains of the Seattle Angina Questionnaire, physical limitations as scored on the SF-36, and exercise capacity as measured on the 6-minute walk test.

Discussant Peter Libby, MD, was effusive in his praise for Dr. Khan’s study.

Bruce Jancin/Frontline Medical News

“This is a wonderful example of how we may be able to offer new hope for patients and families with high Lp(a),” declared Dr. Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

He approved of the methodology and embraced what he called “the intriguing preliminary picture of benefit for lowering Lp(a).”

Most of all, he was pleased that Dr. Khan’s well conducted albeit small study has thrown a spotlight on Lp(a), which he characterized as a greatly underappreciated causal risk factor for a range of cardiovascular diseases.

“Lp(a) stands out like a Manhattan skyscraper as the major driver of calcific aortic stenosis, an epidemic that we see in our aging population,” he observed.

He added that topics worthy of further research with regard to Lp(a)-lowering apheresis as a treatment for refractory angina include the question of whether the mechanism of benefit involves structural changes in atherosclerosis or functional changes. And if it’s the latter, is it a matter of changes in microvascular function, macrovascular function, or a combination of the two?

Apheresis is extremely costly, inconvenient, and invasive, and there are only several dozen apheresis centers in the United States. So the future of Lp(a)-lowering to treat refractory angina, calcific aortic stenosis, and other cardiovascular conditions where elevated Lp(a) is an important player may lie in pharmacotherapy with the PCSK9 inhibitors, Dr. Libby predicted.

He cited “very promising” data showing that evolocumab (Repatha) and alirocumab (Praluent) lower Lp(a) in dose-dependent fashion. Ongoing very large clinical trials with hard clinical endpoints should eventually provide key information regarding the cardiovascular benefits of lowering Lp(a).

“We may be entering an era where we may be able to offer our patients and families – because this is often a familial problem – a non-apheresis approach to controlling what we are learning is a very important causal risk factor for atherosclerosis,” Dr. Libby said.

Patrick M. Moriarty, MD, said in a video interview that he was very intrigued by the results, and “not personally surprised.” They should stimulate interest in cardiologists to start measuring Lp(a) in their patients like those in this study, in whom the disease severity doesn’t match up with the clinical risk factors, said Dr. Moriarty of the University of Kansas, Kansas City.

Dr. Khan’s study was funded by the UK National Institute for Health Research. She reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

Apixaban tablets

Photo courtesy of Pfizer

and Bristol-Myers Squibb

ROME—Novel oral anticoagulants (NOACs) are as effective as warfarin for preventing stroke but may cause less intracranial hemorrhage (ICH) in patients with atrial fibrillation, according to research presented at ESC Congress 2016.

For this study, investigators compared 3 NOACs—dabigatran, rivaroxaban, and apixaban—to warfarin in a “real-world” setting.

They found that patients had a similar risk of stroke regardless of which drug they received.

However, the risk of ICH was lower with dabigatran and apixaban than with warfarin. There was no significant difference in ICH risk between warfarin and rivaroxaban.

Laila Staerk, PhD, of Gentofte Hospital Copenhagen University Hospital in Hellerup, Denmark, presented these results at the congress as abstract 1875.* The study was supported by Velux Foundations.

“There has been a need to investigate safety and effectiveness of NOACs versus warfarin in a ‘real-world’ population, and our Danish registries provide this opportunity,” Dr Staerk said.

The study included 43,299 atrial fibrillation patients from Danish nationwide administrative registries. Roughly 42% of the patients were taking warfarin, 29% were taking dabigatran, 16% were taking apixaban, and 13% were taking rivaroxaban.

“The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials,” Dr Staerk said.

During follow-up, stroke occurred in 1054 patients, and there were 261 intracranial bleeds.

The risk of having a stroke within 1 year was similar between the treatment groups. The absolute standardized risk was 2.01% for warfarin, 2.06% for rivaroxaban, 2.12% for dabigatran, and 2.46% for apixaban.

At 1 year, the standardized absolute risk of ICH was significantly lower in patients treated with dabigatran or apixaban—0.26% and 0.40%, respectively—than in those treated with warfarin—0.60% (P<0.05). The standardized absolute risk of ICH was 0.47% with rivaroxaban, which was not significantly different than the risk with warfarin.

“The results suggest that, although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute 1-year risk of intracranial bleeding,” Dr Staerk said.

“Our results complement the large, randomized, phase 3 trials by providing ‘real-world’ data on stroke and intracranial bleeding with NOACs versus warfarin since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials.”

“Registry studies have some limitations, such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head, randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation.”

*Information in the abstract differs from that presented at the meeting.

Apixaban tablets

Photo courtesy of Pfizer

and Bristol-Myers Squibb

ROME—Novel oral anticoagulants (NOACs) are as effective as warfarin for preventing stroke but may cause less intracranial hemorrhage (ICH) in patients with atrial fibrillation, according to research presented at ESC Congress 2016.

For this study, investigators compared 3 NOACs—dabigatran, rivaroxaban, and apixaban—to warfarin in a “real-world” setting.

They found that patients had a similar risk of stroke regardless of which drug they received.

However, the risk of ICH was lower with dabigatran and apixaban than with warfarin. There was no significant difference in ICH risk between warfarin and rivaroxaban.

Laila Staerk, PhD, of Gentofte Hospital Copenhagen University Hospital in Hellerup, Denmark, presented these results at the congress as abstract 1875.* The study was supported by Velux Foundations.

“There has been a need to investigate safety and effectiveness of NOACs versus warfarin in a ‘real-world’ population, and our Danish registries provide this opportunity,” Dr Staerk said.

The study included 43,299 atrial fibrillation patients from Danish nationwide administrative registries. Roughly 42% of the patients were taking warfarin, 29% were taking dabigatran, 16% were taking apixaban, and 13% were taking rivaroxaban.

“The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials,” Dr Staerk said.

During follow-up, stroke occurred in 1054 patients, and there were 261 intracranial bleeds.

The risk of having a stroke within 1 year was similar between the treatment groups. The absolute standardized risk was 2.01% for warfarin, 2.06% for rivaroxaban, 2.12% for dabigatran, and 2.46% for apixaban.

At 1 year, the standardized absolute risk of ICH was significantly lower in patients treated with dabigatran or apixaban—0.26% and 0.40%, respectively—than in those treated with warfarin—0.60% (P<0.05). The standardized absolute risk of ICH was 0.47% with rivaroxaban, which was not significantly different than the risk with warfarin.

“The results suggest that, although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute 1-year risk of intracranial bleeding,” Dr Staerk said.

“Our results complement the large, randomized, phase 3 trials by providing ‘real-world’ data on stroke and intracranial bleeding with NOACs versus warfarin since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials.”

“Registry studies have some limitations, such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head, randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation.”

*Information in the abstract differs from that presented at the meeting.

Apixaban tablets

Photo courtesy of Pfizer

and Bristol-Myers Squibb

ROME—Novel oral anticoagulants (NOACs) are as effective as warfarin for preventing stroke but may cause less intracranial hemorrhage (ICH) in patients with atrial fibrillation, according to research presented at ESC Congress 2016.

For this study, investigators compared 3 NOACs—dabigatran, rivaroxaban, and apixaban—to warfarin in a “real-world” setting.

They found that patients had a similar risk of stroke regardless of which drug they received.

However, the risk of ICH was lower with dabigatran and apixaban than with warfarin. There was no significant difference in ICH risk between warfarin and rivaroxaban.

Laila Staerk, PhD, of Gentofte Hospital Copenhagen University Hospital in Hellerup, Denmark, presented these results at the congress as abstract 1875.* The study was supported by Velux Foundations.

“There has been a need to investigate safety and effectiveness of NOACs versus warfarin in a ‘real-world’ population, and our Danish registries provide this opportunity,” Dr Staerk said.

The study included 43,299 atrial fibrillation patients from Danish nationwide administrative registries. Roughly 42% of the patients were taking warfarin, 29% were taking dabigatran, 16% were taking apixaban, and 13% were taking rivaroxaban.

“The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials,” Dr Staerk said.

During follow-up, stroke occurred in 1054 patients, and there were 261 intracranial bleeds.

The risk of having a stroke within 1 year was similar between the treatment groups. The absolute standardized risk was 2.01% for warfarin, 2.06% for rivaroxaban, 2.12% for dabigatran, and 2.46% for apixaban.

At 1 year, the standardized absolute risk of ICH was significantly lower in patients treated with dabigatran or apixaban—0.26% and 0.40%, respectively—than in those treated with warfarin—0.60% (P<0.05). The standardized absolute risk of ICH was 0.47% with rivaroxaban, which was not significantly different than the risk with warfarin.

“The results suggest that, although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute 1-year risk of intracranial bleeding,” Dr Staerk said.

“Our results complement the large, randomized, phase 3 trials by providing ‘real-world’ data on stroke and intracranial bleeding with NOACs versus warfarin since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials.”

“Registry studies have some limitations, such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head, randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation.”

*Information in the abstract differs from that presented at the meeting.

ROME—A short-term course of dual antiplatelet therapy (DAPT) may be non-inferior to a longer course in patients who have a certain type of drug-eluting stent (DES), according to research presented at ESC Congress 2016.

Patients in this study, known as NIPPON, had the Nobori bioabsorbable abluminal-coated stent and received 6 months or 18 months of DAPT, which consisted of aspirin plus clopidogrel or ticlopidine.

The results showed similar rates of net adverse clinical and cerebrovascular events, as well as similar rates of bleeding complications, whether patients received DAPT for 6 months or 18 months.

“Based on these findings, a combination of short[-term] DAPT and a newer DES with bioabsorbable abluminal coating should be able to minimize the incidence of thrombotic events and bleeding complications simultaneously,” said Masato Nakamura, MD, PhD, of Toho University Ohashi Medical Center in Tokyo, Japan.

However, Dr Nakamura also noted that this study had limitations, so the results should be interpreted with caution.

Dr Nakamura presented the results at the congress as abstract 2218.

The study enrolled 3775 patients with coronary artery disease or acute myocardial infarction who had undergone percutaneous coronary intervention and stent placement at 130 Japanese institutions.

All patients had received the Nobori bioabsorbable abluminal-coated stent, with DAPT consisting of aspirin (81–162 mg/day) combined with clopidogrel (75 mg/day) or ticlopidine (200 mg/day).

An interim analysis of the study data showed slow enrolment and substantially lower events than expected, so the study was terminated early.

Dr Nakamura presented results from the first 2772 patients to be followed for at least 18 months.

There was no significant difference in the occurrence of the primary endpoint—net adverse clinical and cerebrovascular events—among patients randomized to either short-term or long-term DAPT—1.92% and 1.45%, respectively—confirming the non-inferiority of short-term therapy.

The rate of bleeding events was similar between the treatment arms as well—0.73% in the long-term arm and 0.96% in the short-term arm—as was the rate of stent thrombosis—0.07% in both arms.

“The results of the present study should be interpreted with caution before trying to draw firm conclusions,” Dr Nakamura said. “The interpretation of the NIPPON trial is complicated by the fact that the event rate was lower than the expected incidence of the primary endpoint in both groups. Therefore, the statistical power may not have been adequate to fully assess the risk of [the] primary endpoint.”

Dr Nakamura also noted that the follow-up period may not have been long enough to draw conclusions about the optimum duration of DAPT for patients with DES.

Furthermore, the early termination of the study, in conjunction with the enrollment of relatively low-risk subjects, suggests the study’s results may not be generalizable to high-risk patients. Similarly, as antiplatelet therapy was mainly limited to clopidogrel, the use of more potent antiplatelet agents may have led to different conclusions.

This study was funded by Associations for Establishment of Evidence in Interventions Studies. Dr Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi Sankyo.

ROME—A short-term course of dual antiplatelet therapy (DAPT) may be non-inferior to a longer course in patients who have a certain type of drug-eluting stent (DES), according to research presented at ESC Congress 2016.

Patients in this study, known as NIPPON, had the Nobori bioabsorbable abluminal-coated stent and received 6 months or 18 months of DAPT, which consisted of aspirin plus clopidogrel or ticlopidine.

The results showed similar rates of net adverse clinical and cerebrovascular events, as well as similar rates of bleeding complications, whether patients received DAPT for 6 months or 18 months.

“Based on these findings, a combination of short[-term] DAPT and a newer DES with bioabsorbable abluminal coating should be able to minimize the incidence of thrombotic events and bleeding complications simultaneously,” said Masato Nakamura, MD, PhD, of Toho University Ohashi Medical Center in Tokyo, Japan.

However, Dr Nakamura also noted that this study had limitations, so the results should be interpreted with caution.

Dr Nakamura presented the results at the congress as abstract 2218.

The study enrolled 3775 patients with coronary artery disease or acute myocardial infarction who had undergone percutaneous coronary intervention and stent placement at 130 Japanese institutions.

All patients had received the Nobori bioabsorbable abluminal-coated stent, with DAPT consisting of aspirin (81–162 mg/day) combined with clopidogrel (75 mg/day) or ticlopidine (200 mg/day).

An interim analysis of the study data showed slow enrolment and substantially lower events than expected, so the study was terminated early.

Dr Nakamura presented results from the first 2772 patients to be followed for at least 18 months.

There was no significant difference in the occurrence of the primary endpoint—net adverse clinical and cerebrovascular events—among patients randomized to either short-term or long-term DAPT—1.92% and 1.45%, respectively—confirming the non-inferiority of short-term therapy.

The rate of bleeding events was similar between the treatment arms as well—0.73% in the long-term arm and 0.96% in the short-term arm—as was the rate of stent thrombosis—0.07% in both arms.

“The results of the present study should be interpreted with caution before trying to draw firm conclusions,” Dr Nakamura said. “The interpretation of the NIPPON trial is complicated by the fact that the event rate was lower than the expected incidence of the primary endpoint in both groups. Therefore, the statistical power may not have been adequate to fully assess the risk of [the] primary endpoint.”

Dr Nakamura also noted that the follow-up period may not have been long enough to draw conclusions about the optimum duration of DAPT for patients with DES.

Furthermore, the early termination of the study, in conjunction with the enrollment of relatively low-risk subjects, suggests the study’s results may not be generalizable to high-risk patients. Similarly, as antiplatelet therapy was mainly limited to clopidogrel, the use of more potent antiplatelet agents may have led to different conclusions.

This study was funded by Associations for Establishment of Evidence in Interventions Studies. Dr Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi Sankyo.

ROME—A short-term course of dual antiplatelet therapy (DAPT) may be non-inferior to a longer course in patients who have a certain type of drug-eluting stent (DES), according to research presented at ESC Congress 2016.

Patients in this study, known as NIPPON, had the Nobori bioabsorbable abluminal-coated stent and received 6 months or 18 months of DAPT, which consisted of aspirin plus clopidogrel or ticlopidine.

The results showed similar rates of net adverse clinical and cerebrovascular events, as well as similar rates of bleeding complications, whether patients received DAPT for 6 months or 18 months.

“Based on these findings, a combination of short[-term] DAPT and a newer DES with bioabsorbable abluminal coating should be able to minimize the incidence of thrombotic events and bleeding complications simultaneously,” said Masato Nakamura, MD, PhD, of Toho University Ohashi Medical Center in Tokyo, Japan.

However, Dr Nakamura also noted that this study had limitations, so the results should be interpreted with caution.

Dr Nakamura presented the results at the congress as abstract 2218.

The study enrolled 3775 patients with coronary artery disease or acute myocardial infarction who had undergone percutaneous coronary intervention and stent placement at 130 Japanese institutions.

All patients had received the Nobori bioabsorbable abluminal-coated stent, with DAPT consisting of aspirin (81–162 mg/day) combined with clopidogrel (75 mg/day) or ticlopidine (200 mg/day).

An interim analysis of the study data showed slow enrolment and substantially lower events than expected, so the study was terminated early.

Dr Nakamura presented results from the first 2772 patients to be followed for at least 18 months.

There was no significant difference in the occurrence of the primary endpoint—net adverse clinical and cerebrovascular events—among patients randomized to either short-term or long-term DAPT—1.92% and 1.45%, respectively—confirming the non-inferiority of short-term therapy.

The rate of bleeding events was similar between the treatment arms as well—0.73% in the long-term arm and 0.96% in the short-term arm—as was the rate of stent thrombosis—0.07% in both arms.

“The results of the present study should be interpreted with caution before trying to draw firm conclusions,” Dr Nakamura said. “The interpretation of the NIPPON trial is complicated by the fact that the event rate was lower than the expected incidence of the primary endpoint in both groups. Therefore, the statistical power may not have been adequate to fully assess the risk of [the] primary endpoint.”

Dr Nakamura also noted that the follow-up period may not have been long enough to draw conclusions about the optimum duration of DAPT for patients with DES.

Furthermore, the early termination of the study, in conjunction with the enrollment of relatively low-risk subjects, suggests the study’s results may not be generalizable to high-risk patients. Similarly, as antiplatelet therapy was mainly limited to clopidogrel, the use of more potent antiplatelet agents may have led to different conclusions.

This study was funded by Associations for Establishment of Evidence in Interventions Studies. Dr Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi Sankyo.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.