Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis

The aim of this meta-analysis was to assess the effectiveness and safety of endothelin-receptor antagonist (ERA) in the patients with hypertension. Searches of the PubMed, EMBASE, and CENTRAL databases were conducted to include all the randomized control trials (RCTs). Eighteen trials including 4898 patients were used in the meta-analysis, of which nine were classified as low risk of bias and the other nine as unclear risk of bias. There was no statistically significant difference in all-cause mortality between ERA and placebo groups [6 trials, fixed effects model, RR 1.53 (0.89–2.62); random effects model, RR 1.45 (0.84–2.52)]. ERA significantly reduced 24-h ambulatory blood pressure and sitting blood pressure in patients with hypertension [5 trials, 24-h SBP: WMD −7.65 (−8.95 to −6.36), 24-h DBP: WMD −5.92 (−7.50 to −4.33); 18 trials, SBP: WMD −6.12 (−7.87 to −4.36), DBP: WMD −3.81 (−4.82 to −2.80)]. However, ERA had more adverse events [within 24 h: 3 trials, RR 1.16 (0.82–1.65); after 24 h, 13 trials, RR 1.21 (1.08–1.36)] and severe adverse events than placebo controls [SAE: 9 trials, RR 1.34 (1.13–1.60)]. In addition, there is a potential need for further RCTs that focus on the use of ERA in patients with hypertension.

本荟萃分析旨在评估内皮素受体拮抗剂（endothelin-receptor antagonist, ERA）用于高血压患者的有效性与安全性。本研究检索PubMed、EMBASE及Cochrane对照试验中心注册库（CENTRAL）数据库，纳入所有随机对照试验（randomized control trials, RCTs）。最终纳入18项试验，共计4898例患者，其中9项试验偏倚风险为低水平，剩余9项试验偏倚风险为不明确。
ERA组与安慰剂组的全因死亡率无统计学显著性差异[6项试验，固定效应模型：相对风险（Relative Risk, RR）1.53（0.89–2.62）；随机效应模型：RR 1.45（0.84–2.52）]。
ERA可显著降低高血压患者的24小时动态血压与坐位血压[5项试验：24小时收缩压（Systolic Blood Pressure, SBP）：加权均数差（Weighted Mean Difference, WMD）−7.65（−8.95至−6.36）；24小时舒张压（Diastolic Blood Pressure, DBP）：WMD −5.92（−7.50至−4.33）；18项试验：坐位收缩压：WMD −6.12（−7.87至−4.36）；坐位舒张压：WMD −3.81（−4.82至−2.80）]。
但与安慰剂对照组相比，ERA组不良事件发生率更高[24小时内：3项试验，RR 1.16（0.82–1.65）；24小时后：13项试验，RR 1.21（1.08–1.36）]，严重不良事件（severe adverse events, SAE）发生率亦更高[9项试验，RR 1.34（1.13–1.60）]。
此外，未来仍需开展针对高血压患者使用ERA的额外随机对照试验。