Impact of anemia on major bleeding in patients taking oral anticoagulants for nonvalvular atrial fibrillation

Background Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real‐world settings. Methods We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0–12.9 g/dL; women: Hb of 11.0–11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all‐cause mortality. Results Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p < .001), and HAS‐BLED score was significantly higher in the anemic patients ( p < .001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49–2.58) and 1.48 (1.17–1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39–0.99) and 1.03 (0.76–1.39). Conclusions The severity of anemia in the patients with NVAF on OACs was associated with major bleeding.