The Risk of Emergency Intestinal Bleeding Among Users of Acenocoumarin: A Population-Based Cohort Study

Abstract

In spite of a 10-13 fold increased risk of bleeding, standard doses of coumarin with a target prothrombin time of 2.7-4.5 INR (International Normalized Ratio) are chronically used in the Netherlands by 4-5% of the adult population forty to eighty years old, mainly for the secondary prevention of myocardial infarction. The Dutch Thrombosis Services, who monitor these patients, use less rigorous criteria than the standard studies do. It would not, therefore, be too much of a surprise if the numbers of bleeding complications in practice would be much higher than expected from the standard papers so far. To answer this question the authors studied emergency intestinal bleedings in a population-based cohort study of chronic acenocoumarin users (813 person years) and their age-matched and population-based controls (17,620 person years). Of 142 first bleedings serious enough to require immediate sigmoidoscopy, 35 were connected with acenocoumarin (25%). The overall incidences in the acenocoumarin cohort and the age-matched controls were, respectively, 4.3 and 0.6 bleedings/100 person years, RR (relative risk) 7.09, p < 0.0001. The acenocoumarin bleeders and their controls had symmetric clinical diagnoses and levels of hemoglobin. However, acenocoumarin bleeders were significantly older and more frequently males. The sex- and age-adjusted RRs were, however, only slightly different from the crude data, suggesting no major influence of these asymmetries on the overall results. Prothrombin times in the acenocoumarin bleeders were frequently higher than the target range. In the subjects initially excluded from the controls because they used alternative compounds that enhance bleedings, incidences of bleedings were calculated as well. The incidences were 0.6 bleeding/100 person years (RR 1.01, ns) for the patients receiving NSAIDS (nonsteroidal antiinflammatory drugs); 1.5 (RR 2.50, p < 0.05) for aspirin; and 1.6 (RR 2.67, 0.05 < p < 0.1) for dipyridamole. The authors conclude that in an adult population of 5% acenocoumarin users, about 25% of the emergency intestinal bleedings are connected with coumarin. The numbers of coumarin bleedings are 4-6 times higher than reported so far. They also demonstrate that the risk of bleeding from coumarin far exceeds the risks from alternative oral antithrombotic agents, such as aspirin and dipyridamole.