The association between statin therapy and the incidence of diabetes, microvascular complications, and cardiovascular events in patients without pre-existing cardiovascular disease

초록

Background and aims: Statins reduce cardiovascular risk, but their role in primary prevention and the potential risk of new-onset diabetes mellitus (NODM) remains controversial. This study aimed to assess the association between statin initiation and the incidence of NODM, diabetes-related microvascular complications, and major adverse cardiovascular events (MACE) in individuals without pre-existing cardiovascular disease (CVD) Materials and methods: We analyzed data from the Korean Nationwide Health Insurance Database (2006–2023), identifying individuals without baseline diabetes, CVD, cancer, or prior statin use. Participants who initiated statins within one year of baseline and continued for at least 180 days were classified as statin initiators; others were classified as non-initiators. After 1:1 propensity score matching for age, sex, 10-year cardiovascular risk, and LDL-cholesterol levels, outcomes were assessed over 3 years and across the entire follow-up duration (mean 9.6 years). Outcomes included MACE, defined as ischemic heart disease, ischemic stroke, or cardiovascular death; all-cause mortality; NODM; and diabetes-related microvascular complications, including retinopathy, nephropathy, neuropathy, and diabetic foot disease. Results: Among 1,188,183 statin-eligible individuals based on NCEP ATP III criteria, 208,790 (104,395 per group) were included in the matched analysis. The mean (SD) age was 55.9 (9.0) years, and 36.9% were male. Baseline fasting glucose and LDL-C were 96.1 (11.2) mg/dL and 174.1 (23.9) mg/dL, respectively. Over 3 years, statin initiation was associated with a significantly lower risk of MACE (HR 0.60, 95% CI 0.50–0.65) and all-cause mortality (HR 0.58, 95% CI 0.49–0.68). A modest increase in NODM risk was observed (HR 1.06, 95% CI 1.01–1.12), without a significant increase in microvascular complications (HR 1.10, 95% CI 0.97–1.24). The number needed to treat (NNT) to prevent one MACE was 135, while the number needed to harm (NNH) for one additional NODM case was 552. Over the full follow-up, statin therapy remained associated with lower risks of MACE (HR 0.80, 95% CI 0.77–0.82) and all-cause mortality (HR 0.91, 95% CI 0.87–0.95), with no significant increase in the incidence of NODM or diabetes-related complications. Conclusion: Primary prevention with stain was associated with reduced risk of MACE and all-cause mortality but required monitoring for diabetes risk. A personalized approach is needed to optimize benefits while minimizing potential risks.