ABSTRACTIntroductionAtrial cardiopathy may be associated with an increased risk of stroke independent of atrial fibrillation (AF). In the ARCADIA trial, apixaban was not superior to aspirin in preventing recurrent stroke among patients with a cryptogenic stroke and atrial cardiopathy. We aimed to determine whether the presence of at least one premature atrial complex (PAC), a known harbinger of AF and stroke, would enhance the ability to identify individuals most likely to benefit from apixaban.MethodsIn ARCADIA, atrial cardiopathy was defined by NT‐proBNP > 250 pg/mL, a P‐wave terminal force greater than 5000 μV × ms in lead V1, or a left atrial diameter index ≥ 3 cm/m² on echocardiogram. For the current analysis, the presence of any PAC on the baseline 12‐lead ECG was substituted for the less atrial‐specific NT‐proBNP criterion. The presence of any PAC was also assessed as a sole atrial cardiopathy criterion.ResultsOf the 1015 patients randomized in ARCADIA, 85 had at least one PAC. The revised atrial cardiopathy criteria were met by 593 patients; 301 were randomized to apixaban and 292 to aspirin. The annualized recurrent stroke rates were 3.1% for apixaban versus 4.4% for aspirin (HR 0.71, 95% CI: 0.38–1.34, p = 0.29). No differences in risk of recurrent stroke among participants with PACs, compared to those without PACs, were observed.ConclusionIn patients enrolled in the ARCARDIA trial, utilizing the presence of PACs as a potential marker of atrial cardiopathy did not reveal definitive evidence of benefit of apixaban compared to aspirin.Trial Registration: ClinicalTrials.gov identifier: NCT03192215.