A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes

Hypertension commonly co-exists with diabetes mellitus (DM), and both are closely related to adverse health outcomes. The activation of aldosterone and mineralocorticoid receptor (MR) may play important roles in this process. Therefore, we aim to evaluate the efficacy of MR antagonists on cardiovascular risk factors, including blood pressure (BP), glucose, lipids, renal function, fibrosis and inflammatory and its safety in patients with both hypertension and DM. We searched PubMed, Embase, Web of Science and Cochrane databases for clinical trials published until December 31, 2019. Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included. Mean difference with 95% confidence intervals was used to report outcomes. Eleven randomised placebo-controlled trials with 640 participants were finally included with mean follow-up of 5 months. Compared to placebo, spironolactone significantly reduced office systolic (–6.57, 95%CI: −9.21, −3.93) and diastolic BP (–2.63, 95%CI: −4.25, −1.02) as well as ambulatory BP; increased glycosylated haemoglobin by 0.3 but no clear effect on fasting glucose. Spironolactone induced a significantly reduction of urinary albumin but increased serum creatinine (7.60, 95%CI: 4.94, 10.27) and decreased glomerular filtration rate (–4.28, 95%CI: −6.38, −2.18). Markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP and TNF-α were also decreased after spironolactone therapy. For lipid metabolism, there was no significant difference between groups. Spironolactone mildly increased serum potassium (0.30, 95%CI: 0.23, 0.37). 2.5% subjects treated with spironolactone experienced mild to moderate hyperkalaemia and received medication or dietary advice and another 1.6% developed severe hyperkalaemia and withdrawn from the studies. Spironolactone reduced BP and urinary albumin, improve fibrosis and inflammation, whereas slightly increases the glycosylated haemoglobin and serum creatinine in patients with hypertension and diabetes. Long-term RCTs to assess the effects of spironolactone on cardiovascular events in this population are warranted.

高血压常与糖尿病（diabetes mellitus, DM）合并存在，二者均与不良健康结局密切相关。醛固酮与盐皮质激素受体（mineralocorticoid receptor, MR）的激活可能在这一病理过程中发挥关键作用。因此，本研究旨在评估盐皮质激素受体拮抗剂对高血压合并糖尿病患者的心血管危险因素（包括血压（blood pressure, BP）、血糖、血脂、肾功能、纤维化及炎症指标）的疗效及其安全性。我们检索了PubMed、Embase、Web of Science及Cochrane数据库中截至2019年12月31日发表的临床对照试验。纳入标准为比较螺内酯（spironolactone）与安慰剂在高血压合并糖尿病患者中治疗效果的研究。结局指标采用均数差（mean difference, MD）联合95%置信区间（confidence interval, CI）进行报告。最终共纳入11项随机安慰剂对照试验，涉及640名受试者，平均随访时长为5个月。与安慰剂组相比，螺内酯可显著降低诊室收缩压（-6.57，95%CI：-9.21~-3.93）与诊室舒张压（-2.63，95%CI：-4.25~-1.02），同时亦可有效降低动态血压；其可使糖化血红蛋白水平升高0.3，但对空腹血糖无明确调控作用。螺内酯可显著降低尿白蛋白排泄水平，但会升高血清肌酐浓度（7.60，95%CI：4.94~10.27）并降低肾小球滤过率（-4.28，95%CI：-6.38~-2.18）。纤维化与炎症标志物，包括III型前胶原N端肽（NIIINP）、I型前胶原C端肽（PICP）、高敏C反应蛋白（hs-CRP）及肿瘤坏死因子α（TNF-α），在螺内酯治疗后均显著下降。在脂代谢层面，两组受试者的各项指标无显著差异。螺内酯可轻度升高血清钾离子浓度（0.30，95%CI：0.23~0.37）。2.5%的螺内酯治疗组受试者出现轻中度高钾血症，接受了药物干预或饮食指导；另有1.6%的受试者发生重度高钾血症并退出研究。综上，螺内酯可降低高血压合并糖尿病患者的血压与尿白蛋白水平，改善机体纤维化与炎症状态，但会轻度升高糖化血红蛋白与血清肌酐水平。未来仍需开展长期随机对照试验，评估螺内酯对该人群心血管事件的临床影响。