Risk-Benefit Tightrope for NOAC + DAPT Varies by ACS Type

February 14, 2018

Whether the reduced ischemic risk from adding a novel oral anticoagulant (NOAC) to antiplatelets in patients with acute coronary syndromes (ACS) is worth the increased hazard from major bleeding may depend on the type of ACS, a meta-analysis suggests.

The triple-antithrombotic therapy was followed by a significant drop in risk for cardiovascular (CV) death, MI, or stroke compared with dual-antiplatelet therapy (DAPT) in patients with acute ST-segment elevation MI (STEMI). It was also associated with more major bleeds, but on balance the benefit exceeded harm.

But in patients with ACS consisting of non-STEMI (NSTEMI) or unstable angina, there was no significant effect from NOAC plus DAPT compared with DAPT on the composite clinical endpoint. But here, too, there was a significant jump in risk for major bleeding.

In the STEMI patients, "we observed that the number needed to treat to prevent a thrombotic event was way lower than the number needed to harm to cause a major bleeding," Giulio G. Stefanini, MD, PhD, Humanitas University, Pieve Emanuele-Milan, Italy, told theheart.org | Medscape Cardiology.

"This means that their risk-benefit profile is more favorable than in NSTEMI-ACS patients, in whom the number needed to treat and the number needed to harm almost coincide," said Stefanini.

He is senior author on the meta-analysis encompassing almost 30,000 patients in six trials, published online February 7 in JAMA Cardiology with Mauro Chiarito, MD, Humanitas University, as lead author.

Across the whole study, the number needed to treat to prevent CV death, MI, or stroke was 84, compared with a number needed to harm with a major bleeding event of 105.

Table. Odds Ratios for Clinical Events, NOAC Plus DAPT vs DAPT Alone, Across 29,667 Patients With ACS in Meta-Analysisa

Clinical Endpoint OVERALL: OR (95% CI); P Value STEMI: OR (95% CI); P Value NSTEMI-ACS: OR (95% CI); P Value
CV death, MI, or stroke 0.85 (0.77–0.93); P<0.001 0.76 (0.66–0.88); P<0.001 0.92 (0.78–1.09); P=0.36
Major bleeding 3.17 (2.27–4.42); P<0.001 3.45 (1.95–6.09); P<0.001 2.19 (1.38-3.48); P<0.001
aIncluding the trials APPRAISE, APPRAISE 2, APPRAISE-J, ATLAS-ACS TIMI 46, ATLAS-ACS 2 TIMI 51, and REDEEM.

OR = odds ratio.

 

Solely among the 14,580 patients with STEMI, the number needed to treat to prevent an ischemic event was 63, compared with a number needed to harm with a major bleeding event of 96.

And for the 15,036 patients with NSTEMI-ACS, the number needed to treat was 130, similar to the number needed to harm of 137.

It isn't surprising that the STEMI patients benefited the most from a NOAC plus DAPT, Stefanini said, because they tend to have greater platelet reactivity, higher thrombus burden, and greater 1-year risk for thrombotic events compared with patients with NSTEMI-ACS. Yet the current results may be the first showing that the effects of such triple antithrombotic therapy may differ by type of ACS.

The findings are only hypothesis-generating, Stefanini acknowledged, but he proposed: "Among this high-risk population, meaning STEMI patients, we need to identify which may benefit the most from a more potent antithrombotic strategy. And this means we have to identify the patients who have the lower bleeding risk."

Stefanini reports receiving a research grant from Boston Scientific and speaking or consulting fees from Braun, Biosensors, Boston Scientific, and Edwards Lifesciences. Chiarito had no disclosures

JAMA Cardiol. Published online February 7, 2018. Abstract

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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