Skip the Antiplatelet: OAC Alone Wins for AF Patients With Stable CAD

 A large meta-analysis finds that dropping antiplatelet therapy cuts cardiovascular mortality and bleeding — without raising ischemic risk.

March 2026  ·  Based on findings published in JACC

31%

lower cardiovascular mortality with OAC alone

54%

lower major bleeding risk

~6,000

patients across 6 randomized trials

For patients with atrial fibrillation (AF) who also have stable coronary artery disease (CAD), a long-debated clinical question may now have a definitive answer: oral anticoagulation alone is better than pairing it with an antiplatelet agent.

A new meta-analysis pooling data from six randomized controlled trials — including ADAPT AF-DES, AFIRE, OAC-ALONE, and others — found that OAC monotherapy delivered meaningful reductions in both cardiovascular death and major bleeding, with no increase in heart attacks, strokes, or stent thrombosis.

"The precision of the estimate is so good now that basically there is only harm in using two agents at the same time."

— Marco Valgimigli, MD, PhD, Cardiocentro Ticino Institute

The analysis, published in JACC, covered nearly 6,000 patients followed for up to 30 months. Compared with those on combination therapy, patients on OAC alone had a 31% lower risk of cardiovascular death and a 54% lower risk of major bleeding. Importantly, rates of major adverse cardiovascular events (MACE), MI, and stroke were statistically similar between groups — meaning the bleeding benefit came with no ischemic tradeoff.

In practical terms, the authors estimated that at one year, OAC monotherapy would prevent roughly 6 cardiovascular deaths and 15 major bleeding episodes per 1,000 patients, compared with combination therapy.

Co-author Duk-Woo Park, MD, of Asan Medical Center (Seoul) called the mortality finding the most notable result. Many clinicians have continued dual therapy out of concern about late ischemic events — but this data now challenges that rationale directly.

The findings apply specifically to patients who are beyond the acute post-PCI or post-ACS phase. As Park emphasized, the takeaway is not that antiplatelets are never needed — rather, once a patient has stabilized and is on long-term OAC, simplifying to monotherapy appears both safer and potentially more effective overall.

Valgimigli believes the evidence is now strong enough to influence clinical guidelines, calling for a shift to OAC monotherapy "as early as possible" — a recommendation the ongoing MATRIX-2 trial is expected to refine further.

Source: Gargiulo G, Piccolo R, Park D-W, et al. Anticoagulation alone or with antiaggregation in patients with coronary artery disease: meta-analysis of randomized trials. JACC. 2026; Epub ahead of print.