Abstract / Summary
Medication nonadherence in patients with myocardial infarction (MI) is a key obstacle to managing cardiovascular disease. However, there is a lack of studies, particularly randomized controlled trials (RCTs), focusing on objective measures of medication adherence behavior. This study aimed to (1) characterize daily medication adherence behavior and dose consistency using objective digital bottle cap data in patients post-MI enrolled in the Dapagliflozin in Patients with Myocardial Infarction (DAPA-MI) RCT, (2) identify patient and contextual factors associated with nonadherence, and (3) assess whether dose consistency is associated with adherence over time. DAPA-MI was a phase 3, double-blind, placebo-controlled RCT evaluating the effect of 10 mg of dapagliflozin versus a placebo given once daily, in addition to standard-of-care therapy, on adults hospitalized for MI. This post hoc analysis used 733,490 timepoints from a digital bottle cap that recorded when study drug bottles were opened. Adherence and dose consistency were evaluated using mixed-effects regression. Adherence was defined at the patient-day level as at least one bottle opening on a given day. Dose consistency was derived from the day-to-day variation in timing of the first recorded opening event. Digital cap data were linked with demographic, clinical, behavioral, and contextual variables to assess factors associated with nonadherence and lower dose consistency over time. In total, 2429 participants were included in the analysis. Features associated with lower adherence included age <40 years (odds ratio [OR] 0.47, 99.9% CI 0.23-0.98), current smokers (OR 0.67, 99.9% CI 0.51-0.87), nonworking days, and serious adverse events. Higher adherence was associated with the New York Heart Association (NYHA) functional class III/IV (OR 1.48, 99.9% CI 1.18-1.86), low (<15 min) 7-day average time variance (OR 1.99, 99.9% CI 1.78-2.23), and morning medication use. Lower dose consistency was observed in patients aged 40-50 years (dose consistency ratio [DCR] 1.23, 99.9% CI 1.03-1.47), in current smokers (DCR 1.16, 99.9% CI 1.03-1.31), and on weekends, while patients with severe angina grading (DCR 0.83, 99.9% CI 0.74-0.94) or morning medication use (DCR 0.88, 99.9% CI 0.86-0.90) had higher dose consistency. Patients with early high dose consistency tended to maintain better adherence over time, whereas missed-dose streaks and routine disruptions were associated with worsening consistency. This study demonstrated the value of objective, continuous digital medication adherence behavior monitoring within a large RCT. Unlike studies relying on self-reported or prescription data, it quantified both adherence and dose consistency at scale, revealing a strong association between them. The findings indicate that temporal irregularity of medication taking may serve as a practical behavioral marker for identifying patients at increased risk of future nonadherence. These findings may advance medication adherence behavior research and inform behavior change interventions, remote monitoring strategies, and predictive adherence models.