Efficacy And Safety Of Aldose Reductase Inhibitor For The Treatment Of Diabetic Cardiovascular Autonomic Neuropathy: A Meta-analysis Of Randomized Controlled Trials

Objective: Aldose reductase inhibitors (ARIs), which can specificallyblock the metabolism of the polyol pathway, is a potential therapy to slowor reverse the progression of diabetic cardiovascular autonomic neuropathy(DCAN). The purpose of this study is to review the effectiveness and safetyof ARIs in the treatment of DCAN as determined by five cardiacautonomic neuropathy function tests.Methods: CENTRAL, MEDLINE, EMBASE database (inception toMay2012) were searched to identify randomized controlled trials (RCTs)and non-randomized controlled trials (non-RCTs) investigating ARIs forDCAN with an English-language restriction. The data were analyzed usingRevMan5.0, and heterogeneity between the trials was evaluated usingCochran’s Q-test and I2. Weighted mean differences (WMD) with95%confidence intervals (CIs) were computed for the five cardiac automaticneuropathy function tests to evaluate the effects. Funnel plot and Egger’stest of each outcome are used to evaluate the publication bias.Results: Nine RCTs and one non-RCT met the prerequisites for thisreview. The analysis results showed that ARIs could significantly improvefunction in at least four of the five autonomic neuropathy tests, includingthe resting heart rate variation coefficients (WMD=0.25,95%CI0.02to0.4, P<0.05); the30:15ratio (WMD=0.06,95%CI0.01to0.10, P<0.01), theexpiration/inspiration ratio (WND=0.05,95%CI0.00to0.09, P=0.05) andthe standing-supine systolic blood pressure changes (WMD=-5.94,95%CI-7.31to-4.57, P<0.00001). Glycaemic control found no significantdifference after ARIs intervention. Adverse effects for ARIs treatment wereminimal, except Tolrestat. And no statistical significant publication biaswas found.Conclusions: Based on our results, ARIs could ameliorate cardiacautonomic neuropathy function, especially the mild or asymptomaticDCAN. However, further investigation is required.