Optimal threshold of adherence to lipid lowering drugs in predicting acute coronary syndrome, stroke, or mortality: A cohort study

OBJECTIVE: Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension. DESIGN: Cohort study of new users of LLDs. SETTING: Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016. PARTICIPANTS: Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded. MAIN OUTCOMES MEASURES: Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality. STATISTICAL ANALYSIS: Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment. RESULTS: 52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51–0.54), 0.79 (0.45–0.87), and 0.84 (0.79–0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low. CONCLUSION: In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality.