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Outcomes Associated with Combined Antiplatelet and Anticoagulant Therapy

Samuel Johnson, PharmD, Kaiser Permanente Colorado, Clinical Pharmacy Services, samuel.g.johnson@kp.org,No financial or other potential conflicts of interest exist., Kristina Rogers, PharmD, Kaiser Permanente Colorado, Clinical Pharmacy Services, kristina.r.rogers@kp.org, No financial or other potential conflicts of interest exist., Thomas Delate, PhD, Kaiser Permanente Colorado, Clinical Pharmacy Research Team, tom.delate@kp.org, No financial or other potential conflicts of interest exist

Abstract

BackgroundUse of antiplatelet therapy in combination with oral anticoagulants remains controversial. The objective of this study was to estimate and compare incident adverse and coronary event rates between patients receiving warfarin monotherapy or warfarin and antiplatelet combined therapy.

MethodsThis was a retrospective, longitudinal pharmacoepidemiologic analysis. Adult patients receiving warfarin managed by an anticoagulation service who had documented antiplatelet (aspirin, clopidogrel, and/or dipyridamole) use (combination therapy cohort) or non-use (monotherapy cohort) were identified as of September 30, 2005. Utilizing integrated, electronic medical records, anticoagulation-related adverse events (death, hemorrhage, thrombosis) and coronary events were identified during a six-month follow-up (October 2005 through March 2006). Proportions of events were compared between cohorts. Independent associations between the cohorts and the outcomes were assessed with adjustment for potential confounding factors.

ResultsData from 2,560 monotherapy and 1,623 combination therapy cohort patients were analyzed. Patients in the combination therapy cohort were more likely to have had anticoagulation-related hemorrhages (4.2% vs. 2.0%, unadjusted p<0.001) and coronary events (0.9% vs. 0.3%, unadjusted p=0.009) but not death (0.1% vs. 0.2%, unadjusted p=0.186) or thrombotic events (0.3% vs. 0.4%, unadjusted p=0.812). With adjustment, combined warfarin and antiplatelet use was independently associated with hemorrhagic (OR=2.75; 95% CI 1.44, 5.28) but not coronary (OR=0.99; 95% CI 0.37, 2.62) events.

ConclusionsAt the population level, the hemorrhagic risk associated with warfarin therapy combined with antiplatelet therapy appears to outweigh the benefits. These findings suggest that clinicians should carefully consider risks and benefits when recommending combined antiplatelet therapy for patients on warfarin who do not meet evidence-based criteria for such therapy.

Key Words: anticoagulation • antiplatelet • aspirin • pharmacy • warfarin