依帕司他联合参松养心胶囊对糖尿病CAN患者HRV的影响及安全性评价

Combined Therapy of Epalrestat and Shensong Yangxin Capsules on Heart Rate Variation of Patients with Cardiovascular Autonomic Neuropathy and Drug Safety Evaluation

目的观察依帕司他联合参松养心胶囊对糖尿病心脏自主神经病变(CAN)患者心率变异性(HRV)的影响及用药安全性。方法将60例糖尿病CAN患者随机分为对照组及治疗组各30例,两组间均维持或优化血糖、血压及血脂等多种危险因素控制方案并保持两组间基础用药的平衡,治疗组加服依帕司他和参松养心胶囊,治疗8周后比较两组治疗前后空腹血糖(FPG)、餐后2h血糖(2h PG)、Hb A1c、SBP、DBP、血清总胆固醇(T-CHOL)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)及心率变异性指标:SDNN、SDANN、SDNNI、RMSSD、PNN50、LF、HF及Mean HR的变化情况,评价其临床用药安全性。结果治疗组、对照组治疗前后FPG[(8.4±1.5)mmol/L比(6.7±1.2)mmol/L和(8.3±1.7)mmol/L比(6.6±1.3)mmol/L]、2h PG[(14.5±3.7)mmol/L比(8.2±0.8)mmol/L和(15.1±4.1)mmol/L比(8.3±0.7)mmol/L]、Hb A1c[(8.2±1.0)%比(6.6±0.4)%和(8.3±1.1)%比(6.4±0.5)%]、SBP[(154.7±18.4)mm Hg比(136.8±16.2)mm Hg和(156.5±19.2)mm Hg比(135.5±17.4)mm Hg]、DBP[(97.8±9.7)mm Hg比(73.8±8.5)mm Hg和(97.4±10.0)mm Hg比(72.4±9.4)mm Hg]、T-CHOL[(6.54±1.45)mmol/L比(4.42±1.21)mmol/L和(6.48±1.48)mmol/L比(4.51±1.14)mmol/L]、LDL-c[(3.47±0.26)mmol/L比(2.82±0.14)mmol/L和(3.44±0.19)mmol/L比(2.90±0.18)mmol/L]比较,差异有统计学意义(P均<0.05),两组治疗后上述指标比较,差异均无统计学意义(P>0.05)。治疗组与对照组治疗后SDNN比较[(114.57±17.23)ms比(95.58±14.26)ms]、SDANN[(87.87±10.23)ms比(73.27±11.23)ms]、SDNNI[(71.54±8.35)ms比(46.7±7.58)ms]、RMSSD[(28.2±5.25)ms比(23.43±5.96)ms]、PNN50[(3.12±0.44)%比(1.30±0.34)%]、LF[(320.48±42.32)ms2比(280.52±40.18)ms2]、HF[(211.08±21.79)ms2比(161.56±23.65)ms2]及Mean HR[(72.23±7.74)bpm比(93.9±8.47)bpm],差异有统计学意义(P均<0.05)。两组治疗前后临床用药安全性指标监测无明显变化。结论临床有效控制血糖、血脂、血压等危险因素的基础上加用依帕司他联合参松养心胶囊口服,可明显提高糖尿病CAN患者HRV的时域及频域指标,改善其预后。

Objective To investigate the effect of combined therapy of epalrestat and Shensong Yangxin capsules on heart rate variation（HRV） of patients with cardiovascular autonomic neuropathy（CAN） and drug safety. Methods Sixty CAN patients were randomly divided into control group（n=30） and treatment group（n=30）. Both groups received hypoglycemic drug/insulin, nitrate esters, enteric coated aspirin, statins, blood pressure maintenance, etc to control risk factors. Treatment group received additional epalrestat and Shensong Yangxin capsules. The treatment course lasted for 8 weeks. Fasting plasma glucose, 2h postprandial glucose, Hb A1 c, systolic blood pressure（SBP）,diastolic blood pressure（DBP）, total cholesterol（T-CHOL）, triglyceride（TG）, high-density lipoprotein cholesterol（HDL-C）, low-density lipoprotein cholesterol（LDL-C）, and HRV parameters（SDNN, SDANN, SDNNI, RMSSD,PNN50, LF, HF, and mean HR）were recorded and compared before and after treatment. Drug safety was also evaluated. Results Significant differences in baseline parameters were found between before and after treatment in both groups [Treatment group： FPG： 8.4 ±1.5mmol/L vs 6.7±1.2mmol/L; 2-h PG： 14.5±3.7mmol/L vs 8.2 ±0.8mmol/L;Hb A1c： 8.2% ±1.0% vs 6.6% ±0.4%; SBP： 154.7 ±18.4mm Hg vs 136.8 ±16.2mm Hg; DBP： 97.8 ±9.7mm Hg vs 73.8 ±8.5mm Hg; T-CHOL： 6.54±1.45mmol/L vs 4.42±1.21mmol/L; LDL-C： 3.47±0.26mmol/L vs 2.82±0.14mmol/L. Control group： FPG： 8.3±1.7mmol/L vs 6.6±1.3mmol/L; 2-h PG： 15.1±4.1mmol/L vs 8.3 ±0.7mmol/L; Hb A1c： 8.3%±1.1% vs6.4%±0.5%; SBP： 136.8±16.2mm Hg vs 156.5±19.2mm Hg; DBP： 97.4±10.0mm Hg vs 72.4±9.4mm Hg; T-CHOL： 6.48±1.48mmol/L vs 4.51±1.14mmol/L; LDL-C： 3.44±0.19mmol/L vs 2.90±0.18mmol/L. all P0.05]. No significant difference in the above index was found between two groups after treatment（all P0.05）. After treatment, compared with control group, treatment group had higher SDNN（114.57±17.23 ms vs 95.58±14.26ms）, SDANN（87.87±10.23 ms vs73.27±11.23）, SDNNI（71.54±8.35 ms vs 46.7±7.58ms）, RMSSD（28.2±5.25 ms vs 23.43±5.96ms）, PNN50（3.12%±0.44% vs 1.30%±0.34%）, LF（320.48±42.32ms2 vs 280.52±40.18ms2）, HF（211.08±21.79ms2 vs 161.56±23.65ms2）,and lower mean HR（72.23±7.74 bpm vs 93.9±8.47bpm）, with all P0.05. Clinical drug safety surveillance results showed no change in safety evaluation parameters. Conclusion Additional use of epalrestat and Shensong Yangxin capsules based on effectively management of blood glucose, blood lipids, and blood pressure can obviously improve HRV of patients with CAN, thus improve their prognosis.