Nils Skajaa

TY - JOUR

T1 - Statin Initiation and Risk of Amyotrophic Lateral Sclerosis

T2 - A Danish Population-based Cohort Study

AU - Skajaa, Nils

AU - Bakos, Istvan

AU - Horváth-Puhó, Erzsébet

AU - Henderson, Victor

AU - Lash, Timothy

AU - Sørensen, Henrik Toft

N1 - Publisher Copyright: © 2021 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - 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 ≥40 years of age 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% confidence interval (CI) = 10.6, 12.1] events per 100,000 person-years) and 1,679 among noninitiators (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.

AB - 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 ≥40 years of age 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% confidence interval (CI) = 10.6, 12.1] events per 100,000 person-years) and 1,679 among noninitiators (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.

KW - Amyotrophic lateral sclerosis

KW - Cohort study

KW - Epidemiology

KW - Population-based

KW - Statins

U2 - 10.1097/EDE.0000000000001384

DO - 10.1097/EDE.0000000000001384

M3 - Journal article

C2 - 34183532

VL - 32

SP - 756

EP - 762

JO - Epidemiology (Cambridge, Mass.)

JF - Epidemiology (Cambridge, Mass.)

SN - 1044-3983

IS - 5

ER -