COMPARATIVE EFFECTIVENESS AND HARMS OF SUSTAINED STATIN THERAPY AMONG YOUNG ADULTS
Author(s)
Jaejin An, PhD1, Hui X. Zhou, PhD2, Rachelle A Juan, MPH2, Soonie Choi, MSc2, Stanley Xu, PhD2, Kristi Reynolds, PhD2, Yiyi Zhang, PhD3;
1Kaiser Permanente Southern California, Research Scientist, Pasadena, CA, USA, 2Kaiser Permanente Southern California, Pasadena, CA, USA, 3Columbia University, New York, NY, USA
1Kaiser Permanente Southern California, Research Scientist, Pasadena, CA, USA, 2Kaiser Permanente Southern California, Pasadena, CA, USA, 3Columbia University, New York, NY, USA
OBJECTIVES: Elevated low-density lipoprotein cholesterol (LDL-C) during young adulthood increases the atherosclerotic cardiovascular disease (ASCVD) risk, but the optimal lipid-lowering strategy in this population remains unclear. We compared long-term effectiveness and harms of sustained statin therapy versus no therapy among young adults with elevated LDL-C.
METHODS: We emulated a pragmatic trial of sustained statin therapy versus no therapy using observational data among adults aged 18-39 years from a US integrated health system. Eligible individuals had (1) LDL-C ≥190 mg/dL or (2) LDL-C 130-189 mg/dL and high estimated ASCVD risk (≥7.5% 10-year or ≥20% 30-year risk) between 2008-2017 and were followed through 2022. Sustained statin therapy was defined as initiation and continuous refills without gaps >90 days. Primary outcomes included ASCVD (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and treatment-related adverse events (muscle disorder, liver dysfunction, kidney insufficiency, and new onset type 2 diabetes). We estimated adjusted cumulative risk differences (RDs) and risk ratios (RRs) at 1, 5, and 10 years by applying inverse probability of treatment, adherence, and censoring weights.
RESULTS: We included 10,767 statin initiators and 42,515 non-initiators (overall population mean age 34 years, 28% female, mean LDL-C 181 mg/dL). For ASCVD, adjusted RDs comparing sustained statin versus no therapy were 0.1% (95% CI 0%, 0.2%), -0.2% (95% CI -0.7%, 0.2%) and -1.8% (95% CI -2.4%, -1.3%), at 1, 5, and 10 years, respectively; corresponding RRs were 1.62 (95% CI 0.84, 2.59), 0.79 (95% CI 0.35, 1.18), and 0.33 (95% CI 0.17, 0.48). Statin exposure was associated with higher risks for kidney insufficiency (adjusted RD 0.2%; RR 1.68 at 1 year) and diabetes (adjusted RD 6.2%; RR 1.44 at 10 years). Other adverse events were nonsignificant.
CONCLUSIONS: Among young adults with elevated LDL-C, long-term sustained statin therapy reduced ASCVD. Increased risk of kidney insufficiency and diabetes should be considered in treatment decisions.
METHODS: We emulated a pragmatic trial of sustained statin therapy versus no therapy using observational data among adults aged 18-39 years from a US integrated health system. Eligible individuals had (1) LDL-C ≥190 mg/dL or (2) LDL-C 130-189 mg/dL and high estimated ASCVD risk (≥7.5% 10-year or ≥20% 30-year risk) between 2008-2017 and were followed through 2022. Sustained statin therapy was defined as initiation and continuous refills without gaps >90 days. Primary outcomes included ASCVD (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and treatment-related adverse events (muscle disorder, liver dysfunction, kidney insufficiency, and new onset type 2 diabetes). We estimated adjusted cumulative risk differences (RDs) and risk ratios (RRs) at 1, 5, and 10 years by applying inverse probability of treatment, adherence, and censoring weights.
RESULTS: We included 10,767 statin initiators and 42,515 non-initiators (overall population mean age 34 years, 28% female, mean LDL-C 181 mg/dL). For ASCVD, adjusted RDs comparing sustained statin versus no therapy were 0.1% (95% CI 0%, 0.2%), -0.2% (95% CI -0.7%, 0.2%) and -1.8% (95% CI -2.4%, -1.3%), at 1, 5, and 10 years, respectively; corresponding RRs were 1.62 (95% CI 0.84, 2.59), 0.79 (95% CI 0.35, 1.18), and 0.33 (95% CI 0.17, 0.48). Statin exposure was associated with higher risks for kidney insufficiency (adjusted RD 0.2%; RR 1.68 at 1 year) and diabetes (adjusted RD 6.2%; RR 1.44 at 10 years). Other adverse events were nonsignificant.
CONCLUSIONS: Among young adults with elevated LDL-C, long-term sustained statin therapy reduced ASCVD. Increased risk of kidney insufficiency and diabetes should be considered in treatment decisions.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO44
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory)