Cardioprotective medication adherence in Western Australians in the first year after myocardial infarction: restricted cubic spline analysis of adherence-outcome relationships

Abstract

Adherence to cardioprotective medications following myocardial infarction (MI) is commonly assessed using a binary threshold of 80%. We investigated the relationship between medication adherence as a continuous measure and outcomes in MI survivors using restricted cubic splines (RCS). We identified all patients aged ≥65 years hospitalised for MI from 2003-2008 who survived one-year post-discharge (n = 5938). Adherence to statins, beta-blockers, renin angiotensin system inhibitors (RASI) and clopidogrel was calculated using proportion of days covered to one-year post-discharge (landmark date). Outcomes were 1-year all-cause death and major adverse cardiac events (MACE) after the landmark date. Adherence-outcome associations were estimated from RCS Cox regression models. RCS analyses indicated decreasing risk for both outcomes above 60% adherence for statins, RASI and clopidogrel, with each 10% increase in adherence associated with a 13.9%, 12.1% and 18.0% decrease respectively in adjusted risk of all-cause death (all p < 0.02). Similar results were observed for MACE (all p < 0.03). Beta-blockers had no effect on outcomes at any level of adherence. In MI survivors, increasing adherence to statins, RASI, and clopidogrel, but not beta blockers, is associated with a decreasing risk of death/MACE with no adherence threshold beyond 60%. Medication adherence should be considered as a continuous measure in outcomes analyses.

Figure 1

Fitted adjusted Cox regression restricted cubic spline models and proportion of days covered (PDC) histograms for users by drug group and outcome. The solid line is the adjusted hazard ratio compared to 95% PDC adherence as reference. Dashed lines are the upper and lower 95% confidence limits. The bars are the frequency distribution of adherence by 5% interval. The upper interval includes 100% adherence. Cox regression models with restricted cubic splines were adjusted for: age, sex, Accessibility/Remoteness Index of Australia, history of: hypertension, heart failure, atrial fibrillation, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, stroke, peripheral vascular disease, coronary heart disease, coronary artery revascularisation procedure, coronary heart disease admissions with or without coronary artery revascularisation procedure in the one-year landmark period, and concomitant cardioprotective drugs.