BACKGROUND: 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).
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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).
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Internal Medicine | |
| Cardiology |  |
In patients with AF and ACS/PCI, optimal therapy seems to be a DOAC (here it's apixaban) and a P2Y inhibitor without aspirin. Not shocking news.
These results are important for managing patients with AF and ACS/PCI. I expect we will be seeing many more of these patients on apixaban and clopidogrel as standard therapy. The remaining question may be how long to maintain DOAC + clopidogrel in these patients.
