Bleeding Complications in Patients on NSAIDS and Warfarin, Cox-2 Inhibitor and Warfarin and Warfarin alone

Abstract

The majority of patients requiring warfarin therapy are older and the incidence of comorbidities such as arthritis-related pain is high. These patients frequently require the use of non-selective non-steroidal anti-inflammatory drugs (NSAID) or selective inhibitors of cyclo-oxygenase 2 (COX-2 inhibitors). The concern with combined therapy is an increase in major bleeding events. PURPOSE: We compared the rates of major bleeding complications in two groups of patients: (1) COX-2 inhibitor plus warfarin, (2) NSAID plus warfarin, with a third group: (3) warfarin alone. METHODS: Retrospective analysis was performed using data from our physician supervised Coumadin Clinic. We identified 109 patients taking warfarin plus NSAIDs and 42 patients taking COX-2 inhibitors plus warfarin. We compared rates of bleeding complications in these groups with 255 patients on warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death. RESULTS: In the warfarin-only group the rate for major bleeding events was 3.53% compared to 4.76% in the warfarin plus COX-2 inhibitor group, (p=0.695). In the warfarin + NSAID group the rate for major bleeding events was 2.75% compared to 3.54% in the warfarin only group (p=0.703). CONCLUSIONS: There was a mild but insignificant increase in the rate for major bleeding events in patients taking COX-2 inhibitors and warfarin compared to those taking warfarin alone. There were fewer major bleeding events in the NSAIDs and warfarin group compared to those taking warfarin alone however the decrease was not significant. Preliminary analysis suggests the cautious use of NSAIDs or COX-2 inhibitors in combination with warfarin is not associated with a statistically or clinically significant increased risk of major bleeding events compared to warfarin alone in patients managed carefully in a coumadin clinic.