Discontinuation of anticoagulant treatment: From clinical trials to medication persistence

Abstract

Background: The new generation, non-vitamin K antagonist oral anticoagulants are used in an increasing frequency, partially replacing the vitamin K antagonists in several fields of anticoagulation. Efficacy of the preventive oral anticoagulant regime, however, may be compromised by patient non-compliance. Methods: The authors analyzed treatment discontinuation frequencies in phase 3 trials of anticoagulant treatment in non-valvular atrial fibrillation in a frequentist random effect metaanalysis and in Bayesian multiple treatment network comparison. Results: Frequency of discontinuations are heterogeneous and highly inconsistent (Chi2 test for heterogeneity p>0.001, I2 test for inconsistency 95.1%). Discontinuations were the most frequent with dabigatran followed by rivaroxaban, warfarin, edoxaban and apixaban. Rivaroxaban were less frequently discontinued when compared to the two doses of dabigatran. (OR 0.80; 95% CI: 0.71'0.91 versus 150 mg b.i.d., and OR: 0.77; 95% CI: 0.68'0.87 versus 110 mg b.i.d.). Conclusion: Important differences exist among the treatment adherence of different anticoagulant protocols. Discontinuation rates experienced during the clinical trials may predict the real life patient adherence.