Double vs. Triple Antithrombotic Therapy in PCI and AF

Study Questions:

What are the safety and efficacy outcomes of double vs. triple antithrombotic therapy (DAT vs. TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome who are treated with percutaneous coronary intervention (PCI)?


The authors performed a systematic review and meta-analysis of published randomized clinical trials comparing nonvitamin K antagonist anticoagulant (NOAC) therapy in double (NOAC + single antiplatelet) versus triple (NOAC + dual antiplatelet) therapy. Four trials with 10,234 patients were included. The primary safety endpoint was ISTH major or clinically-relevant nonmajor (CRNM) bleeding. Individual efficacy outcomes included stent thrombosis, all-cause mortality, cardiovascular death, stroke, and overall major adverse clinical events.


DAT was associated with a significantly lower risk of major or CRNM bleeding as compared to TAT (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.56-0.78). DAT was associated with an increased risk of stent thrombosis as compared to TAT (RR, 1.59; 95% CI, 1.01-2.50). There was no difference in the risk of all-cause death or the composite of cardiovascular death, stroke, and major adverse cardiovascular events. Use of NOAC-based DAT was associated with a lower-risk of intracranial hemorrhage as compared to vitamin K antagonist-based TAT (RR, 0.33; 95% CI, 0.17-0.65).


The authors concluded that DAT, especially when using NOAC therapy, is associated with a reduction in bleeding as compared to TAT regimens. However, the authors also note that this benefit in bleeding may be offset by an increased risk of stent-related cardiac events.


Four recently completed randomized trials of a NOAC-based DAT versus a warfarin- or NOAC-based TAT strategy for patients with AF and PCI have each suggested benefit with fewer antithrombotic medications. This meta-analysis confirms this benefit, with a nearly 35% reduction in major and CRNM bleeding risk. It also identified an increased risk of stent thrombosis in the DAT-treated patients. However, it is important to compare the overall number of events: 435 major bleeding events vs. 85 stent thrombosis across the four trials of >10,000 patients. And, there was no difference in cardiovascular death or major adverse clinical events in the two treatment groups. Therefore, for the majority of patients, a DAT strategy using a NOAC is probably safest. But for patients at very high risk of stent thrombosis, a TAT strategy (even if just for a limited time) may be prudent.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Anticoagulation Management and Venothromboembolism, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS, Interventions and Vascular Medicine

Keywords: Acute Coronary Syndrome, Anticoagulants, Atrial Fibrillation, Fibrinolytic Agents, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Percutaneous Coronary Intervention, Secondary Prevention, Stents, Stroke, Thrombosis, Vitamin K, Warfarin, Vascular Diseases, Venous Thromboembolism

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