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Sustained High-Intensity Lipophilic Statin Use and Risk of Age-Related Macular Degeneration: A Target Trial Emulation
Maria Anna Bantounou1, Maria Emfietzoglou1, Tiarnán D L Keenan2
1Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Objective:
To evaluate whether sustained high-intensity lipophilic statin exposure is associated with reduced risk of incident nonexudative age-related macular degeneration (AMD) and progression from nonexudative to exudative AMD.
Design:
Target trial emulation retrospective cohort study.
Participants:
Mass General Brigham data (2005-2025) were used. For incident nonexudative AMD, hypertensive adults aged ≥55 years were classified by high-intensity lipophilic statin exposure (atorvastatin 40-80 mg or simvastatin 40-80 mg) during the 2 years after hypertension diagnosis. For progression to exudative AMD, adults aged ≥55 years with hypertension and nonexudative AMD were classified by exposure during the year before nonexudative AMD diagnosis.
Methods:
Sustained exposure was defined as ≥80% cumulative coverage during the exposure window. Exposed and unexposed individuals were matched 1:1 on demographics, diabetes, obesity, health care use, and calendar time. Subdistribution hazard ratios (sHRs) accounting for death as a competing risk and inverse probability of censoring weighting (IPCW) hazard ratios (HRs) were estimated, adjusting for cardiovascular disease and chronic kidney disease. Sensitivity analyses included positive control (cataract), negative control (posterior vitreous detachment [PVD]), and any statin versus no exposure.
Main Outcome Measures:
Incident clinically documented nonexudative AMD and progression to exudative AMD.
Results:
Over 2.8 ± 1.8 years, nonexudative AMD developed in 68 of 8633 exposed participants (0.79%) and 88 of 8633 unexposed participants (1.02%) (sHR = 0.53, 95% confidence interval [CI], 0.38-0.74; P = 0.0002; IPCW HR = 0.53, 95% CI, 0.37-0.76; P = 0.0005). Over 2.1 ± 1.6 years, exudative AMD developed in 66 of 1082 exposed participants (6.10%) and 85 of 1082 unexposed participants (7.86%) (sHR = 0.62, 95% CI, 0.45-0.87; P = 0.006; IPCW HR = 0.61, 95% CI, 0.43-0.87; P = 0.006). Any statin use was not associated with AMD. For cataract, the sHR was 1.18 (95% CI, 1.03-1.34; P = 0.015), whereas for PVD, the sHR was 1.00 (95% CI, 0.81-1.22; P = 0.96); IPCW HRs were consistent.
Conclusions:
High-intensity lipophilic statin exposure was associated with lower risk of nonexudative AMD and progression to exudative AMD. Confirmation in prospective studies and randomized trials with retinal outcomes is needed.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
