WASHINGTON, D.C.—Six weeks of triple therapy to provide anticoagulation to patients treated with drug-eluting stents was not superior to six months, according to results of the ISAR-TRIPLE trial presented Sept. 15 at the Transcatheter Cardiovascular Therapeutics scientific session. Panelists suggested sample size was a problem.
Nikolaus Sarafoff, MD, of Deutsches Herzzentrum in Munich, outlined the conundrum cardiologists face when treating patients who have atrial fibrillation or otherwise need oral anticoagulants who also are in need of coronary stenting. Dual antiplatelet therapy is better than oral anticoagulation for reducing cardiac events with stenting, while oral anticoagulants beat out dual antiplatelet therapy for reducing the risk of stroke and embolism.
“What to do when a patient has a coronary stent implantation and atrial fibrillation?” he asked. “We have to add both of these therapies. This triple therapy is known to increase the risk of bleeding.”
ISAR-TRIPLE investigators set out to define the optimal duration of triple therapy by randomizing patients to six weeks or six months of clopidogrel (Plavix, Brisotol Myers-Squibb/Sanofi Aventis) plus concomitant aspirin and oral anticoagulation with vitamin K antagonists after implantation with a drug-eluting stent.
They enrolled 307 patients in each arm. More than a quarter of patients in the six-week group continued clopidogrel after six weeks, though.
The primary endpoint was a composite of death, MI, definite stent thrombosis, stroke or TIMI major bleeding at nine months. At nine months, the rate of the primary endpoint was 9.8 percent in the six week group and 8.8 percent in the six month group. “This was not statically different,” Sarafoff observed.
“Six weeks triple therapy is not superior to six months triple therapy with regard to net outcomes,” he said. “Shortening the duration of triple therapy neither reduced the incidence of major bleeding nor increased the incidence of ischemic events.”
The researchers noted that the incidence of MI was higher in the six-week group, but Sarafoff attributed that finding to chance.
Several panelists focused on the sample size of the study. “The number of patients is too small to be conclusive that we can stop safely at six weeks,” said Freek W.A. Verheught, MD, a cardiology professor at Onze Lieve Vrouwe Gasthuis in Amsterdam. Recent guidelines call of six months of therapy, he added.
Gregg Stone, MD, co-director of the Medical Research and Education Division at the Cardiovascular Research Foundation (CRF) and a director at New York-Presbyterian Hospital/Columbia University Medical Center, said the crossover may have diluted differences and that the study may be underpowered. He recommended randomizing patients at six weeks.
Moderator Roxana Mehran, MD, CRF’s chief scientific officer and a professor at Mount Sinai School of Medicine in New York City, emphasized the challenge of conducting such randomized trials. The study underscores “how difficult it is to enroll patients and keep them to the regimen that they are assigned to.”