Intensity of and Adherence to Lipid-Lowering Therapy as Predictors of Major Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease

Abstract

BACKGROUND: The effectiveness of lipid-lowering therapy (LLT) is affected by both intensity and adherence. This study evalu-ated the associations of LLT intensity, adherence, and the combination of these 2 aspects of LLT management with the risk of major adverse cardiovascular events (MACE) in people with coronary heart disease. METHODS AND RESULTS: This is an observational study of all adults who suffered a myocardial infarction or had coronary re-vascularization during 2012 to 2018 and initiated LLT in Stockholm, Sweden. Study exposures were LLT adherence (propor-tion of days covered), LLT intensity (expected reduction of low-density lipoprotein cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity during the previous 12 months were calculated. The primary outcomes were MACE (nonfatal myocardial infarction or stroke and death); secondary outcomes were low-density lipoprotein cholesterol goal attainment and individual components of MACE. We studied 20 490 patients aged 68±11 years, 75% men, mean follow-up 2.6±1.1 years. Every 10% increase in 1-year adherence, intensity, or adherence-adjusted intensity was associated with a lower risk of MACE (hazard ratio [HR], 0.94 [95% CI, 0.93– 0.96]; HR, 0.92 [95% CI, 0.88– 0.96]; and HR, 0.91 [95% CI, 0.89– 0.94], respectively) and higher odds of attaining low-density lipoprotein cholesterol goals (odds ratio [OR],1.12 [95% CI, 1.10–1.15]; OR, 1.42 [95% CI, 1.34–1.51], and OR, 1.16 [95% CI, 1.19–1.24], respectively). Among patients with good adherence (≥80%), the risk of MACE was similar with low-moderate and high-intensity LLT despite differences in the low-density lipoprotein cholesterol goal attainment with the treatment intensities. Discontinuation ≥1 year increased the risk markedly (HR,1.66 [95% CI, 1.23– 2.22]). CONCLUSIONS: In routine care, good adherence to LLT was associated with the greatest benefit for patients with coronary heart disease. Strategies that improve adherence and use of intensive therapies could substantially reduce cardiovascular risk.