In U.S. and European studies, treatment with warfarin plus antiplatelet agents was associated with serious bleeding episodes.
Increasingly, patients are receiving antiplatelet agents plus warfarin when indications exist for both (e.g., atrial fibrillation and coronary stenting). In two studies, researchers examined bleeding complications in such patients.
Italian researchers followed 127 consecutive patients who underwent percutaneous coronary intervention with stenting (resulting in treatment with aspirin plus a thienopyridine [clopidogrel or ticlopidine]) and who also were receiving warfarin (e.g., for atrial fibrillation or prosthetic heart valves). During an average of 6 months on triple therapy (2 antiplatelet drugs plus warfarin), six patients experienced major bleeding complications, which resulted in three deaths related to intracranial bleeding.
In a study from the Kaiser HMO in Colorado, investigators examined bleeding complications among 2560 patients who received warfarin alone and 1623 patients who received both warfarin and an antiplatelet drug (primarily aspirin) during a 6-month period. Major hemorrhage occurred in 1% of patients on warfarin alone and in 2% of those on combination therapy — a significant difference. After adjustment for comorbidities and demographic variables, risk for major hemorrhage still was doubled with combination therapy compared with warfarin alone.
Comment: Not surprisingly, these studies indicate that warfarin plus antiplatelet therapy is associated with substantial risk for serious bleeding. The key question, not addressed directly in these studies, is whether benefits of combination therapies outweigh harms in selected groups of patients. Until that question is answered — ideally by randomized trials — clinicians should use combination antithrombotic therapies only when they believe the indications are compelling.
Triple therapy (warfarin, aspirin, and clopidogrel) could be particularly hazardous. Howard C. Herrmann, MD, deputy editor of Journal Watch Cardiology and director of interventional cardiology at the University of Pennsylvania, suggests that temporary interruption of warfarin therapy should be considered after stenting, particularly in patients at relatively low risk for thromboembolism (JW Cardiol Jun 4 2008). Similarly, the duration of dual antiplatelet therapy in stent recipients who also require anticoagulation should be minimized.
— Allan S. Brett, MD
Published in Journal Watch General Medicine June 26, 2008
Citation(s):
Rogacka R et al. Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oral anticoagulation. J Am Coll Cardiol Intv 2008 Feb 1; 1:56.