Blood Pressure Meds Tied to Lower ALS Risk
Dose-response relationship suggests causal effect, researchers say.
by John Gever John Gever, Managing Editor, MedPage Today November 11, 2014
In a study involving the entire adult population of Taiwan, individuals with amyotrophic lateral sclerosis (ALS) were significantly less likely to have used so-called ACE inhibitors prior to diagnosis than otherwise similar individuals in the general population, researchers said.
Among people whose total ACE inhibitor exposure over a 4-year period exceeded 449.5 times the generally accepted daily dosage, the odds ratio for developing ALS in year five was 0.43 (95% CI 0.26-0.72) relative to nonusers of these medications, according to Charles Tzu-Chi Lee, PhD, of Kaohsiung Medical University Hospital in Taiwan, and colleagues.
The researchers also reported finding a dose-response relationship, in that people who used ACE inhibitors but whose cumulative exposure fell short of the same threshold had a nonsignificantly reduced risk of subsequent ALS diagnosis versus nonusers (OR 0.83, 95% CI 0.65-1.07).
"Our study suggests that ACE inhibitor use has a potential role in the prevention of ALS," Lee and colleagues wrote online in JAMA Neurology, although they acknowledged that the study was limited by its retrospective design and its reliance on administrative records, among other factors.
The researchers sought to examine the possible relationship between ACE inhibitor use and ALS risk because several previous studies, both in humans and in animals, have suggested that the drugs -- commonly prescribed to relieve hypertension -- may have neurotrophic and neuroprotective effects. One rat study, for example, indicated that one such agent reversed motor neuron damage, suggesting a possible relevance to ALS.
Taiwan's universal health insurance program offered a way to examine the possibility in a large population, Lee and colleagues wrote, insofar as it had enrolled some 23 million people nationwide -- 99.6% of the population -- as of 2010, with comprehensive records of medical diagnoses and drugs dispensed.
Out of this large number, Lee and colleagues identified 729 patients with newly diagnosed ALS and matched them on the basis of sex, age, place of residence, and insurance premium type (a marker of employment status) to 14,580 non-ALS individuals. Their records of drug prescriptions filled were examined in the years prior to ALS diagnosis in the patient group, and prior to a corresponding index date in the matched controls.
Besides ACE inhibitor use, the researchers also looked at other common medication types, including other blood pressure reducers, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and corticosteroids.
Histories of ACE inhibitor use were significantly less common in the ALS patients compared with controls: 15.23% of the patients had received such medications, versus 17.99% of the controls. About half as many ALS patients had taken more than 449.5 "cumulative defined daily doses (cDDD) of these medications as did controls. (Lee and colleagues based the cDDD values on published recommended doses for each ACE inhibitor -- for example, 50 mg/day for captopril and 10 mg/day for enalapril.)
None of the other medication classes showed a possible protective effect, although a higher proportion of controls versus patients had exposure to aspirin, a difference that was borderline significant (P=0.05). Users of other NSAIDs, on the other hand, were more likely to be diagnosed with ALS (P=0.03) in unadjusted analyses although the effect size was relatively modest.
After statistical adjustments for factors such Charlson comorbidity score and hospital admissions, light exposure to aspirin (less than 2.4 cDDD) appeared to protect against ALS (OR 0.70, 95% CI 0.55-0.89) but heavier exposure did not. And the only other medication type to show a significant association was ACE inhibitor exposure above 449.5 cDDD.
Factors modifying the relationship between ACE inhibitor exposure and ALS risk included sex (the apparent protective effect was concentrated in males) and age (only those 55 and older showed a significant relationship). On the other hand, there were very few younger patients with high ACE inhibitor exposure and, in those 15 to 54 years old, the odds ratio for ALS among those with more than 449.5 cDDD was 0.49 (95% CI 0.15-1.65).
Besides the retrospective design and reliance on administrative records, study limitations included lack of data on potential confounders such as smoking status, alcohol intake, and vitamin E levels and supplement usage.
Lee and colleagues recommended additional prospective studies to confirm a protective effect for ACE inhibitors, which could also include aspirin.
The study had no external funding.
Authors declared they had no relevant financial interests.
JAMA Neurology
Source Reference: Lee C, et al "Angiotensin-converting enzyme inhibitors and amyotrophic lateral sclerosis risk; A total population–based case-control study" JAMA Neurology 2014; doi: 10.1001/jamaneurol.2014.3367.