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.