Nils Skajaa1, Istvan Bakos, Erzsébet Horváth-Puhó, Victor W Henderson, Timothy L Lash, Henrik Toft Sørensen. 1. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA Department of Epidemiology, Rollins School of Public Health, Emory University, GA, USA.
Abstract
BACKGROUND: The evidence of an association between statins and amyotrophic lateral sclerosis (ALS) is heterogeneous and inconclusive. METHODS: We performed a population-based cohort study consisting of 974,304 statin initiators aged ≥40 years and 1,948,606 matched general population comparators identified from Danish, nationwide registries (1996-2016). We computed incidence rates and hazard ratios (HRs) of a first-time hospital-based diagnosis of ALS. HRs were controlled for sex, birth year, calendar year, medically diagnosed comorbidities, and concomitant medications. RESULTS: During a median follow-up of 7.7 years, 852 ALS events occurred among statin initiators (11.3 [95% CI: 10.6-12.1] events per 100,000 person-years) and 1,679 among non-initiators (11.4 [95% CI: 10.9-12.0] events per 100,000 person-years). The overall adjusted HR indicated a slight association between statin initiation and ALS (1.11 [95% CI: 1.00-1.23]. In the first year after initiation, the HR was 1.40 (95% CI: 1.09-1.79) for both sexes combined, 1.00 (95% CI: 0.70-1.42) for men, and 1.92 (95% CI: 1.30-2.82) for women. The associations diminished to approximately null after the first year of follow-up for both sexes combined and for men, but point estimates were above 1 for women until 10 years after initiation. CONCLUSIONS: Statin initiation was largely unassociated with ALS diagnosis but was associated with an elevated risk of ALS in women, especially in the first year after initiation. The association could be explained by reverse causation, detection bias, early neurotoxic effects of statins that affect women more than men, or a combination thereof.
BACKGROUND: The evidence of an association between statins and amyotrophic lateral sclerosis (ALS) is heterogeneous and inconclusive. METHODS: We performed a population-based cohort study consisting of 974,304 statin initiators aged ≥40 years and 1,948,606 matched general population comparators identified from Danish, nationwide registries (1996-2016). We computed incidence rates and hazard ratios (HRs) of a first-time hospital-based diagnosis of ALS. HRs were controlled for sex, birth year, calendar year, medically diagnosed comorbidities, and concomitant medications. RESULTS: During a median follow-up of 7.7 years, 852 ALS events occurred among statin initiators (11.3 [95% CI: 10.6-12.1] events per 100,000 person-years) and 1,679 among non-initiators (11.4 [95% CI: 10.9-12.0] events per 100,000 person-years). The overall adjusted HR indicated a slight association between statin initiation and ALS (1.11 [95% CI: 1.00-1.23]. In the first year after initiation, the HR was 1.40 (95% CI: 1.09-1.79) for both sexes combined, 1.00 (95% CI: 0.70-1.42) for men, and 1.92 (95% CI: 1.30-2.82) for women. The associations diminished to approximately null after the first year of follow-up for both sexes combined and for men, but point estimates were above 1 for women until 10 years after initiation. CONCLUSIONS: Statin initiation was largely unassociated with ALS diagnosis but was associated with an elevated risk of ALS in women, especially in the first year after initiation. The association could be explained by reverse causation, detection bias, early neurotoxic effects of statins that affect women more than men, or a combination thereof.
Authors: Marc G Weisskopf; Joseph Levy; Aisha S Dickerson; Sabrina Paganoni; Maya Leventer-Roberts Journal: Am J Epidemiol Date: 2022-06-27 Impact factor: 5.363