Antithrombotic Therapy to Minimize Total Events After ACS or PCI in Atrial Fibrillation: Insights From AUGUSTUS.

Limited data exist on the optimal antithrombotic strategy to minimize total bleeding and ischemic events for patients with recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) and atrial fibrillation (AF).The authors sought to identify the antithrombotic regimen that minimized total major or clinically relevant nonmajor bleeding events, ischemic events, and hospitalizations after ACS or PCI in AF.We conducted a secondary analysis of AUGUSTUS (Open-label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), a 2×2 factorial, randomized trial evaluating apixaban vs a vitamin K antagonist (VKA) and aspirin vs placebo in patients with AF and ACS or PCI who were on P2Y₁₂ inhibitor therapy. We determined the incidence of total major or clinically relevant nonmajor bleeding events in patients receiving at least 1 dose of study therapy, total ischemic events, and total hospitalizations among patients randomized to each antithrombotic strategy.Over 6 months of follow-up, 573 of 4,568 (12.5%) patients experienced at least 1 bleeding event while on study drug; among them, 110 (19.2%) had multiple bleeding events. Compared with those with 1 bleeding event, patients with multiple bleeding events were more likely to be on a high-potency P2Y₁₂ inhibitor (prasugrel or ticagrelor vs clopidogrel). Of the 4,614 randomized participants, 219 (4.7%) had at least 1 ischemic event, among whom 75 (34.2%) had multiple ischemic events. At least 1 hospitalization occurred in 1,125 (24.4%) patients; among them, 384 (34.1%) had multiple hospitalizations. Apixaban, compared with VKA, significantly reduced the risk of total bleeding (rate ratio [RR]: 0.66; 95% CI: 0.55-0.80). Apixaban had similar rates of total ischemic events (RR: 0.83; 95% CI: 0.58-1.20) and total hospitalizations (RR: 0.90; 95% CI: 0.79-1.03) compared with VKA. Aspirin, compared with placebo, significantly increased the risk of total bleeding (RR: 2.14; 95% CI: 1.75-2.60). The rates of total ischemic events (RR: 0.75; 95% CI: 0.52-1.08) and total hospitalizations (RR: 1.11; 95% CI: 0.97-1.27) with aspirin and placebo were similar.Among patients with AF and recent ACS or PCI, apixaban significantly reduced total bleeding risk compared with VKA. Aspirin doubled total bleeding risk compared with placebo without a significant change in total ischemic events. Based on this assessment of total events, our findings support the use of apixaban plus a low-potency P2Y₁₂ inhibitor (ie, clopidogrel) without aspirin as the standard therapy for this high-risk patient population. (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart; NCT02415400).

Duke Scholars

Author Renato Delascio Lopes Medicine, Cardiology

Author Christopher Bull Granger Medicine, Cardiology

Author John Hunter Peel Alexander Medicine, Cardiology

Author Daniel Wojdyla  

Author William Schuyler Jones Medicine, Cardiology