The Prevalence and Risks of Inappropriate Combination of Aspirin and Warfarin in Clinical Practice: Results From WARFARIN-TR Study

Background: The use of warfarin and aspirin in combination is restricted to limited patients under relevant guidelines. Aims: To evaluate the prevalence of the inappropriate combination of aspirin and warfarin therapy in daily practice and its risks. Study Design: Cross-sectional study. Methods: The awareness, efficacy, safety, and time in the therapeutic range of warfarin in the Turkish population study is a multi-center observational study that includes 4987 patients using warfarin for any reason between January 1, 2014, and December 31, 2014. To determine the prevalence of inappropriate combination use in daily practice, all patients who had a history of atherosclerotic disease (ischemic heart disease, peripheral artery disease) or cerebrovascular disease (n=1498) were excluded. The data of 3489 patients were analyzed. We defined inappropriate combination as all patients who received aspirin and warfarin regardless of the indication for warfarin use, under the direction of the European Society of Cardiology guideline recommendation. Results: The mean age of patients was 59.2±13.8 years (41.8% male). The prevalence of the inappropriate use of warfarin and aspirin combination was 20.0%. The prevalence of combination therapy in patients with a primary indication for mechanical heart valve, non-valvular atrial fibrillation, and other reasons was 20.5%, 18.7%, and 21.0%, respectively. Multivariate logistic regression analysis revealed that age (odds ratio, 1.009; 95% confidence interval, 1.002-1.015; p=0.010), heart failure (odds ratio, 1.765; 95% confidence interval, 1.448-2.151; p<0.001), smoking (odds ratio, 1.762; 95% confidence interval, 1.441-1.153; p<0.010), chronic kidney disease (odds ratio, 2.057; 95% confidence interval, 1.494-2.833; p<0.001), and deep vein thrombosis (odds ratio, 0.463; 95% confidence interval, 0.229-0.718; p=0.001) were independent predictors of combination therapy (r2=0.66). The mean time in therapeutic range of patients receiving combination therapy was significantly lower than in those on warfarin monotherapy (51.6±27.05 vs. 54.7±23.93; p=0.006). Overall, 19.4% (n=677) of patients had a bleeding event (major bleeding 13.0%, n=88) within a year. Percentages of patients with combination therapy were significantly higher in patients with major bleeding than in patients without major bleeding (29.5% vs. 19.7%; p=0.023). Conclusion: Our study demonstrated that 20.0% of patients taking warfarin use concomitant aspirin inappropriately in daily practice. Patients receiving aspirin with warfarin were demonstrated to have more comorbidities, lower time in therapeutic range levels, and higher bleeding rates.