Medication adherence assessment and reporting in cardiovascular randomised controlled trials

Abstract Background Despite the knowledge that suboptimal adherence to medications may have an impact on the impact of treatment interventions, the assessment and reporting of medication adherence in cardiovascular randomised controlled trials has not been well studied. In this review we sought to study the differences in medication adherence assessment and reporting in cardiovascular randomised controlled trials (RCTs) comparing interventional procedures to medical therapy alone in four major cardiovascular conditions: coronary disease (CAD), atrial fibrillation (AF), heart failure (HF) and hypertension (HTN). Methods Comprehensive searches of PUBMED/MEDLINE, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials (CENTRAL) were performed. Two independent authors screened and extracted general study data, adherence assessment methodology and adherence reporting characteristics from eligible RCTs. Results A total of 568 studies (257 HTN, 120 HF, 116 CAD and 75 AF RCTs) published between 2014–2019 were included in the review. Overall, only 44.7% of RCTs assessed adherence, 14.1% defined “good” adherence and 21.1% reported adherence results. HTN and CAD trials performed significantly better than HF and AF studies in all three parameters. Compared to drug trials, procedural trials were significantly less likely to assess adherence (21.1% vs 45.7%, p<0.001), define good adherence (7% vs 15.5%, p<0.001) or report adherence results (10.5% vs 21.3%, p=0.046). Adherence assessment practices were further significantly influenced by funding, placebo status and study outcome. Pill count/return of packaging was the most utilised method (49.5%) and direct observation the least utilised (1.1%). Adherence was calculated in 55.9% of RCTs with studies using different formulas and setting different thresholds for “good” adherence but most setting this at 80% adherence. Adherence reporting practices also varied significantly between RCTs. Most studies (53%) that assessed adherence, did not in fact report their results. Conclusion Our findings expose significant inconsistencies in adherence assessment and reporting practices amongst cardiovascular RCTs. This is a systemic problem with important implications on research quality and reliability. We therefore recommend the incorporation of mandatory adherence assessment and reporting into international reporting guidelines for RCTs such as the CONSORT statement. We also propose a grading system which once validated may be used to appraise standards of adherence assessment and reporting in RCTs. Funding Acknowledgement Type of funding sources: None.