Dual antithrombotic therapy combined with the blood thinner dabigatran and a P2Y inhibitor could be a more effective—and less risky—alternative to standard care in atrial fibrillation (AFib) patients undergoing percutaneous coronary intervention (PCI), a study published this month in the New England Journal of Medicine reports.
The national standard of care for AFib patients who undergo PCI is triple antithrombotic therapy with warfarin, plus two antiplatelet agents, lead author Christopher P. Cannon, MD, and colleagues wrote in the study, but that course of action can be risky and result in major bleeding events. Recent studies outlined the possible harmful effects of this triple-therapy approach, suggesting the need to identify safer methods of controlling post-PCI and AFib symptoms in tandem.
“In determining the best approach for antithrombotic therapy in patients with atrial fibrillation who are undergoing PCI, if can be difficult to balance the prevention of thrombosis with the risk of bleeding,” Cannon and co-authors wrote. “Oral anticoagulation is indicated in patients with atrial fibrillation for the prevention of stroke and systemic embolism, whereas dual antiplatelet therapy with a P2Y inhibitor plus aspirin is indicated in patients who are undergoing PCI with stent implantation for the prevention of cardiovascular events, including stent thrombosis.”
The researchers recruited 2,725 patients with AFib who were at least 18 years old and had undergone PCI with a bare-metal or drug-eluting stent within 120 hours of the study’s baseline. Between July 2014 and October 2016, these patients underwent randomization at 414 sites across 41 countries, where they either received standard care following their procedure or participated in Cannon et al.’s dual-therapy theory over the course of a year. In the latter cases, patients followed a regimen of dual therapy plus dabigatran, a P2Y inhibitor (either clopidogrel or ticagrelor) and no aspirin.
Cannon’s team found the incidence of the study’s primary endpoint—a major or clinically relevant nonmajor bleeding event during an average 14-month follow-up—was 15.4 percent in their 110-mg dual-therapy group, while that figure was 26.9 percent in the triple-therapy group. Just over 20 percent of patients in the 150-mg dual-therapy group experienced a relevant bleeding event, while the corresponding triple-therapy group’s rate was nearly 6 percent higher, at 25.7 percent. The rate of serious adverse events like myocardial infarction, stroke, systemic embolism or unplanned revascularization didn’t differ significantly between groups, the authors wrote.
The rates of major and total bleeding were significantly lower in both dual-therapy groups than in either triple-therapy group, Cannon and colleagues wrote, resulting in as much as a 48 percent difference in risk between the two.
“The management of atrial fibrillation in patients who have undergone PCI for the treatment of coronary artery disease is a common and difficult challenge,” Jonathan P. Piccini, MD, MHS, and W. Schuyler Jones, MD, wrote in an NEJM editorial accompanying the study. “Although triple therapy may prevent ischemic events, it also has the potential to cause considerable harm in many patients.”
Piccini and Jones wrote that while it’s obvious dual therapy results in decreased risk of major bleeding events, those benefits could come at the cost of a possibly increased risk for other cardiovascular complications and ischemic events.
“No single trial has been adequately powered to completely rule out an increase in ischemic events with dual therapy versus triple therapy,” the doctors wrote. “However, the consistency across these three major trials and the significantly lower risk of bleeding with dual therapy make it hard to argue that triple therapy should be used routinely. The aggregate evidence suggests that the net clinical benefit of dual therapy should give cardiologists confidence to drop aspirin when they are using a contemporary PCI strategy with drug-eluting stents. Moving forward, the key questions will be: What combination of drugs should be included in dual therapy, and how will we test this strategy?”