Lipid-Lowering Therapy Adherence Reduces Cardiovascular Risk in Patients with ASCVD

Adherence to lipid-lowering therapy (LLT) is strongly associated with a reduced risk of cardiovascular events in patients with clinical atherosclerotic cardiovascular disease (ASCVD), according to recent research.1

Despite the high risk of recurrent cardiovascular events in patients with ASCVD, previous registry studies have confirmed the underuse of LLTs in a clinical setting. Most patients do not reach recommended LDL-C goals as a result. Additionally, despite the substantial prevalence of ASCVD in the US (with 24 million affected in 2022), over 40% are not on statins whatsoever.2

“While previous systematic literature reviews have reported an association between statin adherence and risk of cardiovascular outcomes, published data on the impact of adherence to both statin and nonstatin LLTs on cardiovascular outcomes in patients with ASCVD have not been reviewed extensively,” wrote Laney Jones, PharmD, implementation science medical director at Amgen, and colleagues. “Therefore, we performed a systematic review and meta-analysis to determine the impact of adherence to LLT on cardiovascular outcomes in adults with clinical ASCVD.”1

Investigators included retrospective and prospective observational studies examining cardiovascular outcomes associated with adherence or persistence of adult patients (described as age ≥18 years) with clinical ASCVD prescribed any LLT for secondary prevention. Clinical ASCVD was defined as acute coronary syndrome, a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke or transient ischemic attack, or peripheral artery disease.1

LLTs examined in the study included statins (rosuvastatin, pravastatin, fluvastatin, and others), anti-PCSK9 monoclonal antibodies (evolocumab or alirocumab), inclisiran, evinacumab, bempedoic acid, niacin, fibrates, ezetimibe, and bile acid sequestrants. Studies focusing solely on specific subpopulations were excluded.1

The team initially identified 12,466 unique records, of which 39 met the inclusion criteria. Of these, 1 was prospective, 36 were retrospective, and 2 used a nested case-control design. Most participants in the collective studies were men and had an average age of ≥65 years. Among the 6 studies reporting mean length of follow-up, the length ranged from 2.2 to 9.1 years.1

Most studies only reported adherence to statins (n = 33), and the most common measure of adherence was PDC (n = 25), followed by medication possession ratio (n = 8). The most common adherence threshold was 80%; in the studies using a threshold of ≥80%, rates of adherence ranged from 0.8% to 91.2%.1

In the trials utilizing an ≥80% threshold, adherence to LLT was shown to statistically significantly reduce the risk of death (hazard ratio [HR], 0.56; 95% CI, 0.34-0.92; P = 0.0268; I2 95%), major adverse cardiovascular events (HR, 0.77; 95% CI, 0.68-0.86; P = 0.0007; I2 83%), and myocardial infarction (HR, 0.86; 95% CI, 0.79-0.95; P = 0.0147; I2 0%), and displayed non-statistically significant reductions in cardiovascular death (HR, 0.44; 95% CI, 0.12-1.60; P = 0.1528l I2 92%) and ischemic stroke (HR, 0.83; 95% CI, 0.58-1.18; P = 0.1856; I2 52%).1

“Our analysis reaffirms the importance of adherence to, and persistence with, LLTs in the secondary prevention setting, as a strategy to reduce the risk of death and recurrent cardiovascular events,” Jones and colleagues wrote. “The findings of this systematic review may provide valuable insights for physicians managing this high-risk population to guide clinical decision making and optimization of patient care.”1

References

1. Jones LK, East C, Ganda OP, Gionfriddo MR. Adherence to Lipid-Lowering Therapies and Cardiovascular Outcomes in Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2025;14(17):e037530. doi:10.1161/JAHA.124.037530

2. Gu J, Sanchez R, Chauhan A, Fazio S, Wong N. Lipid treatment status and goal attainment among patients with atherosclerotic cardiovascular disease in the United States: A 2019 update. Am J Prev Cardiol. 2022;10:100336. Published 2022 Mar 20. doi:10.1016/j.ajpc.2022.100336