Adherence to direct oral anticoagulants for non-valvular atrial fibrillation in real world settings: a systematic review and meta-analysis.
Problem
Unlike warfarin, direct oral anticoagulants (DOACs) for the prevention of stroke in patients with atrial fibrillation (AF) do not require INR monitoring, however medication adherence remains critical due to the short half-life (~12-24 hours) in the body. Uptake of DOACs is increasing but, in the absence of regular clinical contact, adherence remains a high priority in order to ensure their safety and efficacy. The rationale for the introduction of DOAC treatment over warfarin may be weakened if the benefits of less monitoring and a potentially better safety profile are accompanied by reduced efficacy due to lower adherence. Early clinical trials reported discontinuation rates of between 20-25%. Since then, studies have attempted to measure nonadherence in ‘real world’ settings using observational methodologies.
Approach
The aims were to quantify the extent of nonadherence to DOAC therapy for patients with atrial fibrillation, including rates of DOAC persistence or discontinuation, and to explore the determinants of nonadherence to DOACs.In this systematic review and meta-analysis searches were conducted in Medline, Embase, Elsevier, PsycINFO, and Web of Science, covering the period 1st January 2010 – 30th January 2018. English language observational studies were included if they comprised adults taking any type of DOAC for atrial fibrillation, and measured medication adherence (persistence, self-reported implementation or discontinuation) outcomes. Records were screened, quality assessed using CASP criteria and data extracted by at least two reviewers working independently using EPPIReviewer v4 software. In addition to adherence data, any data on reasons for DOAC discontinuation were also extracted. The review protocol has been registered on Prospero, ID number CRD42016032961.
Findings
13,002 records were identified by the searches after de-duplication and 10, 973 screened by multiple reviewers. 2,029 are currently undergoing screening to bring the review up to date. So far 42 papers have been identified for inclusion in the review. Meta-analyses of discontinuation and persistence rates are in progress but will be available for presentation. All remaining extracted data will be narratively synthesised.
Consequences
Understanding the extent of non-adherence to DOACs is a critical component of managing these medications in everyday practice, and will help inform decision making for clinicians when initiating anticoagulant treatment for the prevention of stroke with AF patients. It is imperative that we understand reasons for non-adherence to provide ‘whole person’ care and support patients appropriately in their medication taking.