Direct Oral Anticoagulants for Secondary Prevention After ACS

Study Questions:

What is the safety and efficacy of direct oral anticoagulant (DOAC) use in addition to antiplatelet therapy after acute coronary syndrome (ACS)?


The authors performed a systematic review and meta-analysis of randomized clinical trials comparing DOAC plus antiplatelet therapy to antiplatelet therapy alone in ACS patients. Six studies met the eligibility criteria. The main outcome was the composite of cardiovascular death, myocardial infarction, and stroke. The main safety outcome was major bleeding.


The six studies included 29,667 patients with ACS (49.1% with ST-segment elevation myocardial infarction [STEMI] and 50.7% with non–ST-elevation [NSTE]-ACS). The primary efficacy endpoint was lower in patients treated with DOAC medications as compared to antiplatelet therapy alone (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.77-0.93). This benefit was even greater for STEMI patients (OR, 0.76; 95% CI, 0.66-0.88), but did not reach statistical significance for NSTE-ACS patients (OR, 0.92; 95% CI, 0.78-1.09). DOAC medications were associated with a higher risk of major bleeding as compared to antiplatelet therapy alone (OR, 3.17; 95% CI, 2.27-4.42).


The authors concluded that there is a differential efficacy for DOAC plus antiplatelet therapy in ACS patients based on their initial clinical presentation.


This study combines different DOAC medications at different doses to try and understand if there is a differential risk benefit to DOAC plus antiplatelet therapy for STEMI versus NSTE-ACS patients. Although they identify that STEMI patients derived benefit from combined “triple therapy” while NSTE-ACS patients did not, this came with a significantly increased bleeding risk. The most attractive treatment option (rivaroxaban 2.5 mg BID plus antiplatelet therapy) based on study size, follow-up, and effect size, is not currently available in the United States. Further studies are needed to explore the mechanisms for benefit of “triple therapy” in STEMI patients that does not appear to exist for NSTE-ACS patients, as well as approaches to better balance efficacy and safety.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Prevention, Anticoagulation Management and ACS

Keywords: Acute Coronary Syndrome, Anticoagulants, Hemorrhage, Myocardial Infarction, Platelet Aggregation Inhibitors, Risk Assessment, Secondary Prevention, Stroke, Vascular Diseases

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