Clot-prevention Therapies: No Clear Answer

Dual antiplatelet blood-thinning therapy (DAPT) immediately after stenting with a drug-eluting device has been shown to prevent major cardiac events and stent thrombosis in most patients. Current American College of Cardiology and American Heart Association guidelines recommend 12 months of therapy post-stenting. But out of concern over potential risks of continuing the drugs longer, or even indefinitely, the US Food and Drug Administration (FDA) asked device manufacturers to study the longer-term consequences of the therapy.

Dual antiplatelet blood-thinning therapy (DAPT) immediately after stenting with a drug-eluting device has been shown to prevent major cardiac events and stent thrombosis in most patients. Current American College of Cardiology and American Heart Association guidelines recommend 12 months of therapy post-stenting.

But out of concern over potential risks of continuing the drugs longer, or even indefinitely, the US Food and Drug Administration (FDA) asked device manufacturers to study the longer-term consequences of the therapy.

In results presented today at the American Heart Association Scientific Sessions in Chicago, IL, researchers who led four international studies, generally described by the FDA as a public/private partnership, reported their findings.

The results provided no simple answer for clinicians wondering how long to continue DAPT—defined as a combination of aspirin and an anti-clotting drug after patients had the intervention.

European researchers who presented their results said in a question-and-answer session that the results, which showed increased risk of bleeding the longer the drugs were continued, would likely influence them to discontinue therapy -- though they differed on at what point. They also stressed that each case needs to be evaluated by the physician, rather than done by following a guideline.

The US researchers were more likely to say they would be inclined to continue DAPT as long as patients were doing well. “It’s not the first time Europeans and doctors here have looked at the same studies and come to different conclusions,” said Kirk Garratt,MD, a cardiology at Lenox Hill Hospital in New York, N in an interview after his presentation. Garratt reported on the TAXUS Liberte Post-Approval Study. In that study, researchers looked at long-term safety and efficacy data for the TAXUS Liberte paclitaxel-eluting stent followed by therapy with prasugrel and aspirin in a broad spectrum of patients.

Though the therapy can result in bleeding, Garratt and colleagues reported only a slight increase in the number of patients who had long-term vs. short-term therapy. “Most bleeds were of moderate intensity, and none were intracranial or lethal,” he said.

Reporting on a related study in Germany, known as ISAR, Stefanie Schulz-Schupke and colleagues reported on safety data for patients getting clopidogrel after drug-eluting stent implantation after 6 months of therapy, vs. 12 months.

The ISAR study also found patients had a higher risk of bleeding at 12 months (7%) than they did at 6 months (3%) with 40 patients having significant bleeds at the 12-month mark, vs. 20 patients at 6 months.

Responding to questions after the presentation, Schulz-Schupke said “In Germany we think it’s safer to shorten the therapy.”

In a third study, conducted by The Harvard Clinical Research Institute and named DAPT, researchers reported on results of giving patients who got a drug-eluting stent a regimen of aspirin and a thienopyridine/ antiplatelet therapy vs. aspirin alone. The study involved only FDA-approved coronary stents. They tracked poor outcomes including stent thrombosis, heart attacks, and stroke.

The findings were reported today by Laura Mauri, MD, MSc, ahead of publication in the New England Journal of Medicine. Mauri, an interventional cardiologist at Brigham and Women’s Hospital, said the results led her and colleagues to believe “the benefits of continuing dual antiplatelet therapy for 30 months were quite remarkable, and that it reduced the relative risk of stent-related blood clots by 71%. “The treatment benefit was larger than anticipated,” Mauri said.

In a second European study, known as ITALIC, researchers concluded that bleeding and thrombosis rates “were not significantly different” between patients who got DAPT for 6 months vs. 24 months, but they concluded that 6 months of DAPT “was non-inferior to 24 months,” as long as patients responded well to aspirin.

Representatives of the FDA were present at the session, and congratulated participants on their studies, but said they were still weighing the data.