Key result
Aldose reductase inhibitors improve resting heart rate variation by ~0.25 vs placebo in diabetic CAN.
Why the study?
Do aldose reductase inhibitors improve cardiovascular autonomic nerve function in patients with diabetic cardiovascular autonomic neuropathy?
Meta-Analysis (n=979)
Do aldose reductase inhibitors improve cardiovascular autonomic nerve function in patients with diabetic cardiovascular autonomic neuropathy?
Aldose reductase inhibitors significantly improve several cardiovascular autonomic reflex tests in patients with diabetic cardiovascular autonomic neuropathy, without affecting glycemic control.
Answers are grounded in this paper and cite their sources.
Aldose reductase inhibitors may improve autonomic function in diabetic neuropathy; extends mixed-trial data but requires updated RCTs before practice change.
BACKGROUND: Aldose reductase inhibitors (ARIs) can block the metabolism of the polyol pathway, and have been used to slow or reverse the progression of diabetic cardiovascular autonomic neuropathy (DCAN). The purpose of this study was to review the effectiveness and safety of ARIs in the treatment of DCAN as determined by five cardiac autonomic neuropathy function tests. METHODS: CENTRAL, MEDLINE, EMBASE, Scopus databases (inception to May 2012) were searched to identify randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) investigating ARIs for the treatment of DCAN with an English-language restriction. The data were analyzed using RevMan 5.0, and the heterogeneity between the trials was evaluated using the Cochrane's Q-test as well as the I² test. The type of model (random or fixed) used for analysis was based on heterogeneity. Weighted mean differences (WMD) with 95% confidence intervals (CI) were computed for the five cardiac automatic neuropathy function tests to evaluate the effects. RESULTS: Ten articles met the prerequisites for this review. Analysis of the results showed that ARIs significantly improved function in at least three of the five automatic neuropathy tests, including the resting heart rate variation coefficients (WMD = 0.25, 95%CI 0.02 to 0.48, P = 0.040); the 30∶15 ratio (WMD = 0.06, 95%CI 0.01 to 0.10, P = 0.010) and the postural systolic blood pressure change (WMD = -5.94, 95%CI -7.31 to -4.57, P = 0.001). The expiration/inspiration ratio showed a marginally significant benefit (WMD = 0.05, 95%CI 0.00 to 0.09, P = 0.040). Glycaemic control was not significantly affected by ARIs. Adverse effects of ARIs except for Tolerestat were minimal. CONCLUSIONS: Based on these results, we conclude that ARIs could ameliorate cardiac automatic neuropathy especially mild or asymptomatic DCAN but need further investigation.
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Hu et al. (2014) conducted a meta-analysis in Diabetic Cardiovascular Autonomic Neuropathy (DCAN) (n=979). Aldose reductase inhibitors (Epalrestat, Ponalrestat, Tolrestat) vs. Placebo was evaluated on Resting heart rate variation coefficients (CV R-R) (WMD 0.25, 95% CI 0.02 to 0.48, p=0.040). Aldose reductase inhibitors significantly improved resting heart rate variation coefficients by a weighted mean difference of 0.25 compared to placebo in patients with diabetic cardiovascular autonomic neuropathy.
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