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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; P < 0.001) and high-dose regimens (LSMD, −9.04 mmHg; 95% CI, −10.99 to −7.08; P < 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; P < 0.001) and high dose (LSMD, −4.17 mmHg; 95% CI, −5.72 to −2.62; P < 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; P < 0.001) and high dose (OR, 11.63; 95% CI, 3.82 to 35.39; P < 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; P = 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.

Trial Registration: PROSPERO Identifier: CRD420251108664

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기사명 저자명 페이지 원문 목차
Efficacy and safety of selective aldosterone synthase inhibitors in uncontrolled hypertension : a systematic review and meta-analysis of randomized controlled trials Abdelaziz Louat, Mohammad Dwikat, Mohamedhen Vall Nounou, Salaheddin M. Abdulhamid, Ali M. Abdelaziz, Amr Ibrahim, Pierre Sabouret, Muhammed Elhadi p. 1-23
Amiloride : revisiting an old drug for resistant hypertension Chan Joo Lee, Sungha Park p. 1-7
Resistance exercise training and blueberry extract protect against cardiac and skeletal muscle remodeling and metabolism disruptions in experimental pulmonary arterial hypertension Leôncio Lopes Soares, Luciano Bernardes Leite, Bruno Rocha Avila Pelozin, Sebastião Felipe Ferreira Costa, Thainá Iasbik-Lima, Patrick Turck, Alex Sander da Rosa Araujo, Flavio Gilberto Herter, Tiago Fernandes, Mariana Machado-Neves, Emily Correna Carlo Reis, Edilamar Menezes Oliveira, Antônio José Natal p. 1-18
Indirect 24-hour blood pressure arterial stiffness indexes and pulse wave velocity : insights from an individual patient data analysis Nikolaos Kakaletsis, Gil F. Salles, Claudia R.L. Cardoso, Vasilios Kotsis, Athanase D. Protogerou, Christina Antza, Elpida Athanasopoulou, Jinho Shin, James E. Sharman, Anastasios Kollias, George S. Stergiou, Christos Savopoulos p. 1-16
Acute effects of isometric plank exercise on 24-hour ambulatory blood pressure in young adults with prehypertension : a randomized cross-over trial Seung Won Jung, Joon Youp Seong, Sunjung Kim, Ho Jeong Min, Tae Gu Choi, Hyun Jeong Kim, Kevin S Heffernan, Sae Young Jae p. 1-11

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