Research: Amiloride for Trials

Epub: Pasternak et al. Use of amiloride and multiple sclerosis: registry-based cohort studies. Pharmacoepidemiol Drug Saf. 2012 May 3. doi: 10.1002/pds.3269.

PURPOSE: Amiloride reduces functional neurological deficits and neuronal damage in animal models of multiple sclerosis (MS). We investigated whether amiloride use was associated with reduced risk of incident MS and of MS hospitalization and death in humans.

METHODS: We conducted two propensity score-matched cohort studies, linking nationwide registry data on filled drug prescriptions, diagnostic information, and covariates. First, we compared rates of incident MS in new users of amiloride and new users of an active control treatment, thiazide diuretics. Second, rates of hospitalizations for MS and of death were compared between users of amiloride and thiazides in a cohort of MS patients. Treatment groups were matched 1 : 4 on propensity scores that included a wide range of covariates, and Cox regression was used to estimate hazard ratios (HRs).

RESULTS: Comparing 36 659 users of amiloride and 177 031 users of thiazides, there were 19 cases of incident MS during 92 548 person-years of follow-up among amiloride users and 81 cases during 567 599 person-years of follow-up among thiazide users. There was no significantly decreased risk of MS associated with amiloride use (HR 1.34, 95%CI 0.81-2.20). In the cohort of MS patients, amiloride use was not associated with significantly decreased risk of MS hospitalization (HR 1.11, 95%CI 0.79-1.59) or death (HR 1.38, 95%CI 0.83-2.28).

CONCLUSION: Amiloride use was not associated with significantly decreased risk of incident MS or hospitalizations and death among patients with MS. Because amiloride users were represented by older patients, risks could not be evaluated in younger individuals.

Amiloride is an inhibitor of acid sensing ion channel t(ASICSI) that will help limit the ionic loading that can trigger nerve damage as we have discussed previously, but it is also used as a diruetic to reduce high blood pressure. Thiazide diuretics are also used to reduce high blood pressure.This group aimed to see if there was any evidence of influence of MS based on prescriptions for the drug and information about MS diagnosis. They found that a diagnosis of MS was as common in amiloride users as thiazide users. 

However a sample size of 19 is very low to base ideas on and importantly the science indicates that amiloride is not viewed as a diesase modifying drug. It does not stop animals from developing MS-like disease but limits nerve damage as a consequence of the disease. Maybe one would hope that it would slow the accumulation of disability that can result in death and this risk was not reduced significantly with less death although it was 1.4 times less. The number of amiloride using MSers is just too low to make any conclusions. There is a clinical trial that aims to investigate whether amiloride can slow down inflammatory nerve damage. If positive it could benefit all MSers. Yet’s hope so.

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