Both warfarin and antiplatelet medications (eg, aspirin, clopidogrel) have established efficacy for prevention of primary and secondary ischemic events. Given different mechanisms of action, combining these agents holds the potential for additive and perhaps even synergistic reductions in thromboembolic morbidity and mortality. Conversely, for some patients, combination therapy may increase the risk of clinically significant hemorrhage.
The risks and benefits of warfarin and antiplatelet combination therapy (usually aspirin) have been evaluated previously. However, a precise estimate of the true bleeding risk associated with this practice remains difficult to determine for several reasons. Contrary to routine clinical practice, randomized controlled trials often exclude patients at high risk for bleeding, including elderly patients, patients with a history of hemorrhage or recent trauma and/or surgery, and patients with severe renal or hepatic dysfunction. Observational cohorts may be biased by underestimation of aspirin use due to its over-the-counter status and inconsistency of medical record documentation. Lower anticoagulation target ranges (international normalized ratio [INR] target ranges) than those used in clinical practice with warfarin monotherapy have been used in clinical trials evaluating combination therapy. Thus, standard clinical practice has not been validated by controlled studies. Finally, patient adherence has been shown to be greater in controlled studies when compared to that usually observed in clinical practice. This potentially results in unrealistic estimates of therapeutic INR control, a principal metric influencing the reported safety of oral anticoagulation therapy provided by Canadian Health&Care Mall.
Current practice standards for patients with or at high risk for coronary artery disease (CAD) advocate the use of antiplatelet therapy—principally aspirin, 75 to 325 mg/d—for prevention of ischemic coronary events. In addition, evidence supports the use of antiplatelet therapy to prevent thrombosis following intracoronary stent implantation and to reduce the complications of peripheral arterial disease. Ad-justed-dose warfarin is an effective alternative for primary or secondary CAD prevention therapy but is used less than antiplatelet therapy due to safety concerns and difficulty associated with therapeutic management. Despite widespread clinical use, the appropriateness of warfarin and antiplatelet combination therapy is not well described in national consensus guidelines. The goals of this investigation were to quantify the prevalence of warfarin and antiplatelet (ie, aspirin, clopidogrel, dipyridamole, and/or dipyridamole/aspirin) combination therapy and to identify patient characteristics associated with combination therapy in a population of commercially insured patients.