Adherence to secondary prevention medications and four-year outcomes in outpatients with atherosclerosis

Background: Although nonadherence with evidence-based secondary prevention medications is common in patients with established atherothrombotic disease, long-term outcomes studies are scant. We assessed the prevalence and long-term outcomes of nonadherence to secondary prevention (antiplatelet agents, statins, and antihypertensive agents) medications in stable outpatients with established atherothrombosis (coronary, cerebrovascular, or peripheral artery disease) enrolled in the international REduction of Atherothrombosis for Continued Health registry. Methods: Adherence with these medications in eligible patients at baseline and 1-year follow-up was assessed. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke at 4 years. Results: A total of 37,154 patients with established atherothrombotic disease were included. Adherence rates with all evidence-based medications at baseline and 1 year were 46.7% and 48.2%, respectively. Nonadherence with any medication at baseline (hazard ratio, 1.18; 95% confidence interval, 1.11-1.25) and at 1 year (hazard ratio, 1.19; 95% confidence interval, 1.11-1.28) were both significantly associated with an increased risk of the primary end point. The risk of all-cause mortality was similarly elevated. Corresponding numbers needed to treat were 31 and 25 patients for the composite end point and total mortality, respectively. This also was true for each disease-specific subgroup. Patients who were fully adherent at both time points had the lowest incidence of adverse outcomes, whereas patients who were nonadherent at both time points had the worst outcomes (P <.01). Conclusions: Our analysis of a large international registry demonstrates that nonadherence with evidence-based secondary prevention therapies in patients with established atherothrombosis is associated with a significant increase in long-term adverse events, including mortality.