麻豆传媒

WASHINGTON -- Limiting the length of triple therapy for stent patients who require anticoagulation does not increase the benefit or reduce the risk in this population, researchers reported.

The ISAR-TRIPLE investigators compared a 6-week regimen of warfarin, aspirin, and clopidogrel to a 6-month regimen and at 9 months found the the incidence of major adverse cardiovascular events (MACE) plus major bleeding was 9.8% in the 6-week group and 8.8% in the 6-month arm.

Only 4.3% of patients in the control group and 4% of those in the 6-week group met the prespecified secondary endpoints of cardiac death, myocardial infarction, stent thrombosis, or ischemic stroke. the study's lead investigator from Deutsches Herzzentrum, Munich and Klinikum der Universität Munich, said that difference, too, was not significant.

Sarafoff reported the results from the tudy in a late-breaking clinical trial session at the meeting here.

He noted that patients with atrial fibrillation, pulmonary embolism, deep vein thrombosis, or mechanical valves pose a clinical challenge when they require percutaneous coronary interventions because, "physicians are in a clinical dilemma as to what to prescribe," given the need for both antiplatelet and anticoagulant protection.

It is well-recognized that the risk of stent thrombosis is greatest in the weeks immediately following PCI, whereas the risk of bleeding increases with the length of therapy and intensity of anticoagulation.

Sarafoff and colleagues investigated the treatment length issue in a prospective, randomized, open-label trial in an effort to determine the optimal duration of triple-therapy after stent implantation.

They recruited 614 from September 2008 through December 2013. All patients had DES and randomization to 6 weeks, or 6 months of triple therapy was done after implantation.

Sarafoff said the trial was built on the finding from the WOEST trial, which investigated the use of aspirin after stenting.

In ISAR-TRIPLE, all patients received aspirin and warfarin as background therapy. The critical question was the discontinuation of the antiplatelet therapy -- clopidogrel -- at 6 weeks or 6 months.

Addressing the bleeding issue, Sarafoff said there were no differences in BARC measures between the two groups. However, in a post-hoc landmark analysis, researchers found a reduction in the 6-week group in BARC bleeding with the shorter therapy group: 20% versus 27%.

Researchers found no clear differences in patient characteristics. The average age of patients was 74, roughly 25% were women, and a third presented with acute coronary syndrome.

There were, however, more MIs in the 6-week group -- 2% versus zero in the 6-month arm -- but Sarafoff told 麻豆传媒, "we think this was likely the play of chance."

said the study design might have been improved by delaying randomization until the very last moment, to avoid the risk of distorting "the signal to noise ratio." Stables served as a TCT discussant for the study.

Sarafoff conceded that randomization at 6 weeks would have given a clearer picture of what happened; however, he noted that randomization at 6 weeks would have been more difficult to perform in an investigative trial because it requires more manpower and time.

"I'm very surprised that there's no difference in bleeding," said Bern University Hospital. He added that he could see no explanation. In clinical practice bleeding under triple therapy is supported by large scale observational data. "My take-home from this is that I'd rather shorten triple therapy in order to avoid the risk of bleeding."

A closer look at outcomes in the early stages of the study, between baseline and 6 weeks, with respect to cardiac death, myocardial infarction stent thrombosis, and ischemic stroke, showed a slightly higher incidence in the 6-week group in comparison with the 6-month group.

However , of the University of Paris, said he believed the differences were mostly due to the study's low numbers. In lower-power studies, attention to confidence intervals is important, he notes. In trials like this one that are low-powered, readers should be wary about overinterpreting the shape of the curve.

"The reality is you're just seeing noise. A couple of patients going either way gives an apparent separation of the curve."

Asked what impact this might have on practice, Steg said, "We can't have definitive guidance on the basis of under-powered studies. The best we can do is pool them with other studies and try to get some sense of where to go."

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