While rare, major bleeding events in patients with stable coronary artery disease (CAD) are independent predictors of death, according to a new study.

Researchers prospectively analyzed 4,184 consecutive patients with stable CAD from the CORONOR study who were free from any myocardial infarction (MI) or coronary revascularization for more than a year at the time of inclusion. The majority of patients were male, aged 66.9 ± 11.5 years, and had undergone at least one coronary revascularization procedure before inclusion in the analysis. The majority of patients (n = 2,798) received single antiplatelet therapy.

To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with stable CAD, the researchers used a number of statistical analytics.

A total of 271 deaths (119 cardiovascular and 152 non-cardiovascular) were reported at follow-up, along with 91 MIs and 48 strokes. The combined clinical endpoint was reported in 226 patients, with 51 major bleeding events during follow-up. Gastrointestinal bleeding was the primary bleeding site in 54.9% of the cases. When used as a time-dependent variable, major bleeding was linked with a significant increase in mortality (HR = 6.78; p < 0.0001). This association remained significant when adjusting for a number of other factors (HR = 2.89; p < 0.0001), including age, sex, diabetes, prior heart failure, and estimate glomerular filtration rate.

Vitamin K antagonists were associated with increased bleeding risk, especially when combined with antiplatelet therapy. The results were enough for the authors to urge caution in the use of some combinations of antiplatelet therapies.

"For the clinician, the important take-home message is to avoid long-term use of antiplatelet agents in combination with oral anticoagulation in stable CAD patients, and to consider coprescription of a proton-pump inhibitor, given that many events in these patients are related to gastrointestinal bleeding," they wrote, adding that the results were not generalizable to patients within 1 year of an MI or coronary revascularization.

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Hamon M, Lemesle G, Tricot O, et al. J Am Coll Cardiol. 2014;64:1430-36.

Keywords: Vitamin K, Coronary Artery Disease, Myocardial Infarction, Stroke, Follow-Up Studies, Platelet Aggregation Inhibitors, Heart Failure, Glomerular Filtration Rate, Hemorrhage, Diabetes Mellitus

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