Riluzole is associated with reduced risk of heart failure

Abstract

Background: Reduction of intracellular Na⁺ accumulation through late Na⁺ current inhibition has been recognized as a target for cardiac Ca²⁺ handling which underlies myocardial contractility and relaxation in heart failure (HF). Riluzole, an Na⁺ channel blocker with enhancement of Ca²⁺-activated K⁺ channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca²⁺ leak and therefore may improve cardiac function.

Objectives: The study aim was to investigate whether riluzole lowers HF incidence.

Methods: Rates of HF incident were compared using a commercial insurance and Medicare supplement claims databases. Patients with a filled riluzole prescription (treatment) between 06/2009 and 12/2019 were compared to those with no-riluzole (control). We excluded HF patients during the 180-day baseline period. Study endpoint was the first HF diagnosis from the index riluzole prescription or ALS diagnosis. HF onset was compared between the propensity score matched treatment and control cohorts.

Results: The matched cohort consisted of 4060 pairs of riluzole/control patients. The 24-month cumulative incidence of HF onset for riluzole versus control patients was 4.96% versus 7.27%, calculating hazard ratio (HR) [95% CI, p-value] of 0.55 [0.40-0.76, p < 0.01]. The HR estimates favoring riluzole over the ALS control were consistent across the 3 months to 2-year follow-up. The clinically and statistically significant effect on HF onset was driven by the lower rate of HFrEF with the 2-year HR [95% CI] of 0.46 [0.21-0.99].

Conclusions: Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management.

Keywords: Riluzole; heart failure; small conductance Ca2+‐activated K+ channels; sodium channels.

FIGURE 1

Cohort Extraction Flow Chart. *Analytic Cohort for HF admission: Patients may or may not have diagnoses of HF during the baseline period.

FIGURE 2

Two‐year cumulative incidence and hazard ratio estimates of HF onset for riluzole: Matched cohort.

FIGURE 3

Two‐year cumulative incidence and hazard ratio estimates by HF subtype (HFpEF and HFrEF): Matched cohort analysis.