Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly

Objective: Statins are commonly prescribed drugs that have been inconsistently associated with amyotrophic lateral sclerosis (ALS) risk. We examined associations between ALS risk and overall statin use, statin categories based on lipophilicity and other cholesterol-lowering medications, in Medicare beneficiaries. Methods: In this nation-wide population-based case-control study, 10,450 Medicare participants (ages 66-89 years) diagnosed with ALS, using Medicare Parts A and B claims, between 1 January 2008 and 31 December 2014, were frequency-matched to 104,500 controls on age, sex, and selection year. Odds ratios (ORs) for the association between statins and ALS were estimated using logistic regression models. Covariates included dyslipidemia, other comorbidities, age, sex, race, proxies for smoking and obesity, Medicare use, and indicators of socioeconomic status. Statin use derived from Medicare Part D claims. Non-statin cholesterol-lowering drugs were evaluated as comparison drugs. Results: ALS risk was reduced with statin use (OR = 0.87 (95% confidence interval (CI) = 0.83-0.91)). While risk was unrelated to three cholesterol-lowering medications (nitrates, bile acid sequestrants, and ezetimibe), it was associated with fibrates (OR = 0.88 (95% CI = 0.80-0.97)). Risk for lipophilic statins was slightly lower than for other statins. ALS risk was lower in all statin categories for dyslipidemic individuals, but only lipophilic statins were associated with lower risk in non-dyslipidemic individuals and demonstrated an inverse trend with duration. Conclusions: Our findings suggest that statins are associated with lower ALS risk and offer new evidence that fibrates may be related to lower risk. However, we were unable to fully adjust for smoking and body mass index.