Incidence, Source, Determinants, And Prognostic Impact Of Major Bleeding In Outpatients With Chronic Heart Failure: Insights From The CARDIONOR Registry

Abstract

Risk, correlates, and consequences of major bleeding as well as the frequency of antithrombotic use in heart failure (HF) patients are largely unknown. We analyzed incident major bleeding during a 3-year follow-up in 2910 HF outpatients included in the prospective multicenter CARDIONOR registry. Major bleeding was defined as a type ≥ 3 bleed using the Bleeding Academic Research Consortium (BARC) definition and adjudicated by a blinded committee. Most patients were male (62%) with a mean age of 71.6 ± 12.8 years. The mean LVEF was 48 ± 13% with proportions being 50% for preserved, 24% for mid-range, and 26% for reduced LVEF. Altogether, 45% of the patients had a history of CAD. The NYHA class was ≥ 3 in 22.8% of the cases. There was a high prevalence of AF at inclusion (57.3%). At inclusion, most patients (89%) received at least one antithrombotic: anticoagulation (54%) and/or antiplatelet therapy (46%). Major bleeding occurred in 111 patients (3-year cumulative incidence: 3.6% [95%CI: 3.0-4.3]). Most events were BARC 3a (32.5%) or 3b (31.5%). Most frequent sites of bleeding were gastrointestinal (40.6%) and intracranial (27.9%). Anticoagulation was used in 82% of the patients at time of major bleeding. Variables associated with major bleeding were atrial fibrillation (P < 0.0001), diabetes (P = 0.012), and older age (P = 0.049). The incidence of bleeding was similar in HF patients with preserved, mid-range or reduced left ventricle ejection fraction (LVEF), with mild or severe HF symptoms, and with ischemic or non-ischemic HF. Major bleeding was strongly associated with mortality (adjusted hazard ratio: 5.63; 95% CI 4.37–7.24; P < 0.0001). In HF outpatients, major bleeding occurs at a stable rate of 1.2% annually and is associated with a dramatic increase in mortality. Most events occur in patients receiving anticoagulation. The risk of bleeding is similar in patients with preserved, mid-range, or reduced LVEF.