By David Douglas
NEW YORK (Reuters Health) - 28/6/2019
A regimen of vitamin K antagonists (VKAs) plus dual antiplatelet therapy (DAPT) is best avoided in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), according to a network meta-analysis of randomized controlled trials.
As Dr. Renato D. Lopes of Duke Clinical Research Institute, Durham, North Carolina, told Reuters Health by email, "after this comprehensive study in a challenging field of antithrombotic therapies . . . we learned that less is more. A double regimen that includes a P2Y12 inhibitor and a non-VKA oral anticoagulant (NOAC) - instead of warfarin - gives us the best net clinical benefit and aspirin can be safely discontinued for most patients." The new research, online June 19 in JAMA Cardiology, looked at four trials involving more than 10,000 patients.
The overall prevalence of acute coronary syndrome (ACS) varied from 28% to 61%. The patients' mean age ranged from 70 to 72 years and 20% to 29% were women. Most were at high risk for thromboembolic and bleeding events.
Compared with a reference regimen of VKA plus DAPT (a P2Y12 inhibitor plus aspirin), the odds ratio (OR) for major bleeding was 0.58 for VKA plus a P2Y12 inhibitor (95% confidence interval, 0.31 to 1.08). For a NOAC plus P2Y12 inhibitor, it was 0.49 (95% CI, 0.30 to 0.82) and for a NOAC plus DAPT, 0.70 (95% CI, 0.38 to 1.23).
Corresponding ORs for major adverse cardiovascular events (MACE) were 0.96, 1.02 and 0.94, all spanning unity.
"Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE," the team writes.
"So," concluded Dr. Lopes, "longer-term triple therapy is not needed for the majority of patients. If one decides to use triple therapy and keep aspirin longer for more uncommon cases, then it is better to do it with a NOAC as the oral anticoagulant and not with warfarin."
Dr. Marc Peter Bonaca, director of Vascular Research at the University of Colorado School of Medicine, in Aurora, told Reuters Health by email, "I think this is an important paper and clearly shows that dropping an antiplatelet agent (aspirin) reduces bleeding. This is reassuring from a safety perspective and shows consistency between the trials."
"What remains uncertain is what the cost is in terms of ischemic benefit. It would stand to reason that less potent strategies (e.g. dropping aspirin) might increase MACE risk yet none of the individual trials or this meta-analysis excludes a MACE hazard from dropping aspirin," said Dr. Bonaca, who was not involved in the work.
"In fact," he concluded, "the OR for MACE have upper confidence intervals of 1.45 to 1.47 meaning the strategy could be more than 40% worse from an ischemic perspective. So for high-bleeding-risk patients, dropping aspirin will reduce bleeding. For high-ischemic-risk patients at a low risk of bleeding, the risk of dropping aspirin remains uncertain."
The study had no commercial funding.
JAMA Cardiol 2019.