Nils Skajaa

TY - CONF

T1 - Statin initiation and risk of amyotrophic lateral sclerosis: Danish population-based cohort study

AU - Skajaa, Nils

PY - 2020/9/16

Y1 - 2020/9/16

N2 - ABSTRACTBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with insidious onset. The evidence of an association between statins and 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 1 January 1996 to 31 December 2016 from Danish, nationwide registries. We computed cumulative incidences, treating death as a competing risk, incidence rates and Cox regression derived hazard ratios (HRs) of a first-time hospital-based discharge diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, age, 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). Adjusted HRs 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 1.33 (95% CI: 1.08–1.64) for both sexes combined, 0.95 (95% CI: 0.71–1.26) for men, and 2.04 (95% CI: 1.40–2.97) 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. We obtained a similar pattern of sex differences in a sensitivity analysis altering the comparator cohort to those initiating angiotensin-converting enzyme inhibitors. 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 - ABSTRACTBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with insidious onset. The evidence of an association between statins and 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 1 January 1996 to 31 December 2016 from Danish, nationwide registries. We computed cumulative incidences, treating death as a competing risk, incidence rates and Cox regression derived hazard ratios (HRs) of a first-time hospital-based discharge diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, age, 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). Adjusted HRs 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 1.33 (95% CI: 1.08–1.64) for both sexes combined, 0.95 (95% CI: 0.71–1.26) for men, and 2.04 (95% CI: 1.40–2.97) 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. We obtained a similar pattern of sex differences in a sensitivity analysis altering the comparator cohort to those initiating angiotensin-converting enzyme inhibitors. 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.

M3 - Poster

T2 - ICPE All Access

Y2 - 16 September 2020 through 17 September 2020

ER -