Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.
A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.
Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).
“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.
The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”
The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”
All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.
Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.
The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.
The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
Guidelines upside down?
In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.
“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.
In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.
“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.
“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”
In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”