Adherence to statins with risk of cardiovascular and limb events in peripheral artery disease

Background Given the markedly elevated risk of cardiovascular and limb events in peripheral artery disease (PAD), guidelines recommend high-intensity statins in PAD patients to lower this risk. However, adherence to statin medications remains suboptimal, especially in PAD patients, compared with other atherosclerotic cardiovascular diseases. Purpose To investigate the association between statin adherence and cardiovascular events, limb events, and mortality in PAD. Methods The Peripheral Artery Disease: Long-term Survival (PEARLS) is a longitudinal registry of patients with new-onset PAD during 2015-2020 in the U.S. Veterans Affairs Health System. Patients with PAD are identified based on abnormal ankle brachial and toe-brachial index extracted using a validated natural language processing system. Data on key clinical variables including prescription filled are available. Within the registry, we identified patients with persistent statin use in the year following their PAD diagnosis. Statin adherence was assessed during the year after PAD diagnosis by calculating proportion of days covered (PDC) and categorized PDC as >0.90, 0.80 to <0.9, 0.60 to < 0.8, and <0.6. In dichotomous analyses, adherence was defined as PDC ≥ 0.80. Study outcomes included cardiovascular events (hospitalization for myocardial infarction or stroke), limb events (chronic limb threatening ischemia and major amputation), and overall mortality. Last follow up was 31/12/2024. We conducted multivariable hierarchical logistic regression modelling to identify variables associated with adherence. To evaluate associations between statin adherence and cardiovascular events, limb events, and mortality, we developed multivariable Cox proportional hazards models. Results We identified 56,034 PAD patients with persistent statin use. The majority (53%) had PDC > 0.90 (IQR: 0.76-0.98), and 54% were on a high-intensity statin at baseline. Several patient variables were associated with statin adherence, especially Black race and Hispanic ethnicity which were associated with 43% and 25% lower odds of adherence (Table 1). In multivariable Cox regression models, we found a graded association between poor adherence and clinical events (Figure 1). Compared to reference group (PDC >0.90), patients with lowest adherence (PDC<0.6) had 32% higher hazard of cardiovascular events (HR 1.32; 95% CI: 1.25-1.39) and 28% higher hazard of limb events (HR 1.28; 95% CI: 1.18-1.38). Poor adherence to statins was also associated with higher mortality (HR 1.08; 95% CI: 1.04–1.13). Conclusion Although overall adherence to statins was high among persistent users, Black race and Hispanic ethnicity were associated with lower adherence. Low statin adherence was associated with higher risk of cardiovascular events, limb events, and mortality suggesting that overcoming barriers to adherence can mitigate the risk of cardiovascular and limb events, especially in those at the highest risk.