Experts debate long-term DAPT for patients with prior MI

BOSTON — The optimal duration of dual antiplatelet therapy continues to be debated, and two experts at the Cardiometabolic Health Congress deliberated the pros and cons of long-term therapy in patients with prior MI.

Long-term dual antiplatelet therapy (DAPT) in patients with prior MI brings with it an increased risk of bleeding, but that is outweighed by an absolute risk reduction in ischemic events, according to A. Michael Lincoff, MD, director of the Cleveland Clinic Coordinating Center for Clinical Research. Lincoff said continuing DAPT beyond the recommend 12 months, possibly with a lower dose anti-clotting agent, was more effective than aspirin therapy alone.

A. Michael Lincoff

Interest in long-term DAPT follows the recent publication of the PEGASUS-TIMI 54 trial, which examined long-term ticagrelor (Brilinta, AstraZeneca) plus aspirin in patients with prior MI who were not in the typical window for acute therapy, Lincoff said. In PEGASUS-TIMI 54, participants were randomly assigned 60 mg or 90 mg ticagrelor plus aspirin or matching placebo. Those assigned ticagrelor exhibited a significant reduction in ischemic events during a 16-month period with both doses.

“Now, this was associated with an increased risk of bleeding … but what was important, was that the higher dose (90 mg) … actually had the higher risk as compared to the lower dose (60 mg) — and thus leading to the idea that we step down on the intensity of the therapy for long-term,” Lincoff said.

A recent meta-analysis of trials that evaluated longer-term therapies in patients with prior MI, including PEGASUS-TIMI 54 and CHARISMA, yielded similar results, according to Lincoff.

“When these trials are combined, the story is quite consistent,” he said. “There is a reduction in ischemic events … with an absolute risk reduction in ischemic events of about 1.1 events per 100 patients treated.” However, “this does come at an increased risk of bleeding, and it’s about a twofold increased risk. So there is an off-setting, but, in general, we consider these bleeding events, although important, not as important as the irreversible events of death, MI, stent thrombosis, etc.”

Debating the opposite position, John W. Eikelboom, MBBS, MSc, associate professor at McMaster University, Hamilton, Ontario, Canada, said use of long-term DAPT is hardly a settled argument.

“It’s time for a reality check,” Eikelboom said. “Should [DAPT] be continued indefinitely in patients with prior MI? Absolutely not.”

Eikelboom acknowledged that there is a rationale for treating with long-term DAPT “hinting at a benefit,” but individual trials, he said, provide no evidence of a net benefit for extended therapy. While long-term DAPT may prevent recurrent MI and stent thrombosis, it can also increase bleeding risk and does not improve survival. He cited a recent meta-analysis published in the European Heart Journal that failed to show that long-term treatment with “expensive, potent medications” improves survival, a key measure of net benefit.

“We don’t have quality-of-life data, but the two things we care about are being alive and being well,” Eikelboom said. “Why treat when we have no evidence that either of those two criteria are met?”

Results of the DAPT trial, however, did show a reduction in relative risk for MI, stroke and stent thrombosis in patients continuing the therapy for 30 months compared with patients taking aspirin alone. However, there was no reduction in CV mortality, and a doubling of non-CV mortality, he said. A subsequent meta-analysis of DAPT trials showed a neutral effect on CV death, Eikelboom said.

“Extended DAPT reduces some important events, but increases other important events and does not produce a net benefit for our patients if used long-term,” Eikelboom said. “Routine extended DAPT costs money, it adds to the burden of pill taking … and in the absence of a net benefit, it is a distraction from other worthwhile therapies.” – by Regina Schaffer

Editor’s note: The stances taken by each debater were for educational purposes and do not necessarily reflect their own views.

Reference:

Eikelboom JW, Lincoff AM. Expert debates in antithrombotic therapy. Presented at: Cardiometabolic Health Congress; Oct. 21-24, 2015; Boston.

Disclosure: Eikelboom reports receiving honoraria and research support from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen and Pfizer. Lincoff reports receiving research grants from AstraZeneca, CSL Laboratories, Eli Lilly, Regado, Roche, Takeda and Vivus through his institution.