Switching between direct oral anticoagulants: a systematic review and meta-analysis

Crossover between direct oral anticoagulants (DOACs) has been underinvestigated, but happens frequently in clinical practice. It is still unknown whether DOACs have similar rates of switch, or whether some DOACs are more prone to be switched over time. We reviewed studies comparing DOAC-to-DOAC switch prevalence, and compared risk of switch depending on index DOAC through meta-analysis. Systematic review followed PRISMA guidelines and deposited protocol (PROSPERO#CRD42020152405). MEDLINE, EMBASE, and Cochrane-CENTRAL were searched up to 1/3/2020 for studies reporting on DOAC-to-DOAC switch. We determined by meta-analysis the pooled odds ratio (OR) for switch depending on index DOAC prescribed. Newcastle-Ottawa Scale was used for bias assessment. Among 221 results retrieved, 5 large studies (n = 259,308, mean age ranging 61.2-79.3) provided data on DOAC-to-DOAC switch. Studies were all large retrospective, observational and claims registry-based, with similar ascertainment of exposure and switch. Bias assessment revealed fair to high quality. Among DOACs, apixaban had consistently lower risk of DOAC-to-DOAC switch compared to dabigatran (OR 0.29, 95% CI 0.25-0.34) or rivaroxaban (OR 0.58, 95% CI 0.50-0.67), the former carrying a higher risk than the latter (OR 2.35, 95% CI 1.93-2.86). Results were robustly confirmed by sensitivity analysis. Apixaban might carry a lower risk of DOAC-to-DOAC switch compared to dabigatran and rivaroxaban. Further studies are needed to confirm long-term safety and effectiveness of switching paradigm.