Atrial-fibrillation patients with a recent acute coronary syndrome or percutaneous coronary intervention should be given apixaban and a P2Y12 inhibitor without aspirin for the first 6 months, new study results suggest. Ralf E. Harskamp, MD, PhD, of Academic Medical Center, Amsterdam, and colleagues presented these findings from a post hoc analysis of the AUGUSTUS trial in a paper published online Monday and in the Feb. 8 issue of the Journal of the American College of Cardiology. AUGUSTUS was a 2x2 factorial trial that randomized patients with atrial fibrillation (AF) who had acute coronary syndrome (ACS) or who underwent percutaneous coronary intervention (PCI) to receive apixaban or a vitamin K antagonist (VKA), and to receive aspirin or a placebo, for 6 months. It found that the use of a P2Y12 inhibitor with an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without a significant difference in the incidence of ischemic events as compared with regimens that included a VKA or aspirin. In the post hoc analysis, baseline risk for bleeding were assessed using HAS-BLED scores, and baseline risk for stroke was assessed with CHA2DS2-VASc scores, at time of randomization. The authors defined both HAS-BLED and CHA2DS2-VASc scores ≤2 as low risk and scores ≥3 as high risk, based on consensus guidelines for bleeding and stroke risk in AF patients. Of 4,614 patients enrolled in AUGUSTUS, 4,386 were included in the current analysis; 228 were excluded because of missing data required to calculate HAS-BLED or CHA2DS2-VASc scores. The patients’ median age at baseline was 71 years, and the cohort was predominantly white (92.6%) and male (70.6%). Patients with higher bleeding risk also had higher stroke risk , and the reverse was also true (P < 0.001). Patients with high bleeding and stroke risk were more likely to have been taking oral anticoagulants before enrollment and less often received prasugrel or ticagrelor compared with those with lower bleeding or stroke risk. Among patients with ACS as the index event, those with high bleeding or stroke risk were more often medically managed compared with those with lower risk profiles. Of the 4,386 analyzed patients, 66.8% had HAS-BLED ≥3 and 81.7% had CHA2DS2-VASc ≥3. Bleeding rates were lower with apixaban than VKA regardless of patients’ baseline risk (HAS-BLED ≤2 – hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.41-0.78; HAS-BLED ≥3 – HR 0.72, 95% CI: 0.59-0.88. Aspirin increased bleeding irrespective of baseline risk (HAS-BLED ≤2 – HR: 1.86; 95% CI: 1.36-2.56; HAS-BLED ≥3 – HR: 1.81; 95% CI: 1.47-2.23). Apixaban lowered the risk of death or hospitalization in comparison with VKA regardless of stroke risk (CHA2DS2-VASc ≤2 – HR 0.92, 95% CI: 0.67-1.25; HR: 0.82; CHA2DS2-VASc ≥3 – 95% CI: 0.73-0.94). There was no significant interaction between treatment effect and stroke or bleeding risk. Harskamp and colleagues concluded that an antithrombotic regimen including apixaban is associated with less bleeding and hospitalization compared with a regimen with VKA or aspirin, regardless of baseline bleeding or stroke risk. These findings support the use of apixaban, and possibly other direct oral anticoagulants, and a P2Y12 inhibitor without aspirin for most patients with AF who present with ACS or undergo PCI, the authors wrote. In an accompanying editorial, Pascal Vranckx, MD, PhD, from Jessa Ziekenhuis and Hasselt University, Belgium, and colleagues, wrote that it was not surprising that the authors found no difference in outcomes across bleeding and stroke risk categories because neither the HAS-BLED nor CHA2DS2-VASc scores were designed to guide antithrombotic regimens in patients like those in the AUGUSTUS trial. “As such, risk scores based on baseline variables, even when useful to improve the accuracy of the prognostic assumptions affecting clinical decisions, cannot be considered a clear-cut decision rule or a substitute for case-by-case critical judgment,” the editorialists write. The AUGUSTUS trial was supported by Bristol Myers Squibb and Pfizer. Sources: Harskamp RE, Fanaroff AC, Lopes RD, et al. Antithrombotic Therapy in Patients With Atrial Fibrillation After Acute Coronary Syndromes or Percutaneous Intervention. J Am Coll Cardiol 2022;79:417–427. Vranckx P, Angiolillo DJ, Valgimigli M. Patients With Atrial Fibrillation and PCI or ACS: Does Predicted Risk Matter? J Am Coll Cardiol 2022;79:428–431. Image Credit: Soni's – stock.adobe.com