More Bleeding With Prolonged Dual Antiplatelet Therapy

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

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

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

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

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

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

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.