Incidence, Source, Determinants, and Prognostic Impact of Major Bleeding in Outpatients With Stable Coronary Artery Disease

Study Questions:

What is the incidence and impact on outcome of bleeding in patients with stable coronary artery disease (CAD) who are at least 1 year past any coronary events (any myocardial infarction [MI] or revascularization)?


This was a prospective multicenter study of 4,184 consecutive patients with stable CAD. Stable CAD was defined as documentation of CAD with no MI and/or any coronary revascularization for at least 1 year at inclusion. Participants had a 2-year clinical follow-up. The objectives of the analysis were to determine the incidence, source, determinants, and prognostic impact of major bleeding in the cohort. Bleeding events were classified using the Bleeding Academic Research Consortium (BARC) definition; major bleeding was defined as all BARC type ≥3 events.


There were 51 major bleeding events during the 2-year follow-up (0.6 per 100 patient-years); in most cases (54.9%), the site of bleeding was gastrointestinal. In adjusted analyses, major bleeding was significantly associated with mortality (hazard ratio, 2.89; 95% confidence interval, 1.73-4.83; p < 0.0001). Older age, diabetes mellitus, and lower estimated glomerular filtration rate (eGFR) were independent predictors of major bleeding in multivariable analysis. A substantial proportion of patients received dual antiplatelet treatment with aspirin and clopidogrel (n = 861; 20.8%); 11.1% of patients received a vitamin K antagonist (VKA). Most patients receiving a VKA were also prescribed an antiplatelet agent (n = 342). The increased risk of bleeding associated with VKA treatment was particularly evident when VKA was combined with antiplatelet therapy (APT); furthermore, the risk of cardiovascular death, MI, or nonhemorrhagic stroke was not different in those who received VKA and APT, versus those receiving VKA alone.


Although major bleeding events are rare (0.6%/year) in patients with stable CAD, they are an independent predictor of death. The concomitant use of oral anticoagulation and APT increased risk of bleeding in this analysis without decreasing risk for ischemic events.


The authors deliver an important message that cautions against the long-term use of APT in patients with stable CAD receiving a VKA. Current European and American guidelines suggest the use of VKA monotherapy in patients with atrial fibrillation and stable vascular disease (i.e., >1 year with no acute events), highlighting the risks associated with concomitant use of VKA and APT. The current analysis adds strength to these recommendations, demonstrating increased bleeding (without reduction in ischemic events) in patients receiving both VKA and APT.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Incidence, Coronary Artery Disease, Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Anticoagulants, Atrial Fibrillation, Glomerular Filtration Rate, Ticlopidine, Aspirin, Hemorrhage, Diabetes Mellitus

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