Louat Abdelaziz, Dwikat Mohammad, Nounou Mohamedhen Vall, Abdulhamid Salaheddin M, Abdelaziz Ali M, Ibrahim Amr, Sabouret Pierre, Elhadi Muhammed
Faculty of Medicine and Pharmacy of Casablanca, University of Hassan II, Casablanca, Morocco.
Faculty of Medicine, An-Najah National University, Nablus, Palestine.
Clin Hypertens. 2025 Dec 1;31:e41. doi: 10.5646/ch.2025.31.e41. eCollection 2025.
Earlier Aldosterone synthase inhibitors (ASIs) were non-selective, with a risk of cortisol insufficiency. A new generation of ASIs has emerged with improved selectivity and pharmacological properties, although their efficacy and safety remain debated. This meta-analysis evaluates the efficacy and safety of selective ASIs in adults with uncontrolled primary hypertension. We selected randomized controlled trials (RCTs) from 6 databases/registries, comparing selective ASIs with placebo in adults aged ≥ 18 years with primary uncontrolled hypertension. Quality was assessed using the risk of bias 2 tool. Random-effects models were used to pool mean differences for continuous variables and calculate odds ratios (ORs) for binary outcomes. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Five RCTs, involving 2,456 patients, were included. Least-squares mean (LSM) systolic blood pressure (SBP) was significantly lower with ASIs than placebo in both standard-dose (difference in LSM [LSMD], -9.05 mmHg; 95% confidence interval [CI], -10.98 to -7.12; < 0.001) and high-dose regimens (LSMD, -9.04 mmHg; 95% CI, -10.99 to -7.08; < 0.001). LSM diastolic blood pressure was also significantly lower with ASIs using standard dose (LSMD, -3.54 mmHg; 95% CI, -4.99 to -2.09; < 0.001) and high dose (LSMD, -4.17 mmHg; 95% CI, -5.72 to -2.62; < 0.001) compared with placebo. For safety endpoints, mild hyperkalemia (5.5-6 mmol/L) was more frequent with ASIs at both standard dose (OR, 7.50; 95% CI, 2.46 to 22.85; < 0.001) and high dose (OR, 11.63; 95% CI, 3.82 to 35.39; < 0.001). The rate of moderate-to-severe hyperkalemia (greater than 6 mmol/L) was comparable between the ASI and placebo groups for standard doses. In contrast, high doses were associated with an increased rate in the ASI group (OR, 4.43; 95% CI, 1.10 to 17.82; = 0.036). The certainty of evidence was high for both SBP and mild hyperkalemia, and moderate for moderate to severe hyperkalemia. Selective ASIs appear to be a promising treatment in terms of efficacy and safety for uncontrolled hypertensive patients. Larger RCTs with extended follow-up periods are warranted to establish long-term evidence.
PROSPERO Identifier: CRD420251108664.
早期的醛固酮合酶抑制剂（ASIs）是非选择性的，存在皮质醇不足的风险。新一代的ASIs已经出现，其选择性和药理特性有所改善，尽管它们的疗效和安全性仍存在争议。这项荟萃分析评估了选择性ASIs在未控制的原发性高血压成人患者中的疗效和安全性。我们从6个数据库/登记处中选择了随机对照试验（RCTs），比较了选择性ASIs与安慰剂在年龄≥18岁的原发性未控制高血压成人患者中的效果。使用偏倚风险2工具评估质量。随机效应模型用于汇总连续变量的平均差异，并计算二元结局的比值比（ORs）。使用推荐分级评估、制定和评价方法对证据的确定性进行评级。纳入了5项RCTs，涉及2456例患者。在标准剂量（最小二乘均值[LSM]差异[LSMD]，-9.05 mmHg；95%置信区间[CI]，-10.98至-7.12；P<0.001）和高剂量方案（LSMD，-9.04 mmHg；95% CI，-10.99至-7.08；P<0.001）下，与安慰剂相比，ASIs治疗时LSM收缩压（SBP）显著更低。使用标准剂量（LSMD，-3.54 mmHg；95% CI，-4.99至-2.09；P<0.001）和高剂量（LSMD，-4.17 mmHg；95% CI，-5.72至-2.62；P<0.001）的ASIs治疗时，LSM舒张压也显著低于安慰剂。对于安全性终点，在标准剂量（OR，7.50；95% CI，2.46至22.85；P<0.001）和高剂量（OR，11.63；95% CI，3.82至35.39；P<0.001）下，ASIs治疗时轻度高钾血症（5.5 - 6 mmol/L）更为常见。标准剂量下，ASI组和安慰剂组中重度高钾血症（大于6 mmol/L）的发生率相当。相比之下，高剂量时ASI组的发生率增加（OR，4.43；95% CI，1.10至17.82；P = 0.036）。SBP和轻度高钾血症的证据确定性高，中度至重度高钾血症的证据确定性为中度。就疗效和安全性而言，选择性ASIs似乎是未控制高血压患者的一种有前景的治疗方法。有必要进行更大规模、随访期更长的RCTs以确立长期证据。
PROSPERO标识符：CRD420251108664。
