Efficacy and safety of aldosterone synthase inhibitors in hypertension: A systematic review and meta- analysis

Abstract

Hypertension is a prevalent condition that significantly contributes to cardiovascular morbidity and mortality worldwide. Aldosterone, a key hormone in the regulation of blood pressure, has been implicated in the pathophysiology of hypertension, leading to increased interest in aldosterone synthase inhibitors (ASIs) as a therapeutic option. This meta-analysis aims to systematically evaluate the efficacy and safety of ASIs in reducing blood pressure and associated adverse events in older adults with hypertension, providing a comprehensive overview of current evidence to inform clinical practice.

A comprehensive electronic search was conducted using PubMed, Google Scholar, Cochrane Central, and Clinicaltrials.gov were extensively searched till 31 December,2023. Out of 729 articles identified through our search strategy, 6 randomized controlled trials met the eligibility criteria and were included in the meta-analysis. The studies varied in sample size, duration, and specific ASIs evaluated, focusing on older adults with hypertension. Baseline characteristics and outcomes were extracted using an online Excel sheet, summarising parameters such as age, sex, race, BMI, and duration of hypertension. The Cochrane risk of bias tool was utilised to assess the quality of included trials across five domains: selection, reporting, performance, detection, and attrition bias. Statistical analyses were performed using RevMan version 5.4, applying random effects models for forest plots with a significance level set at p<0.05.

The meta-analysis found that aldosterone synthase inhibitors (ASIs) significantly reduced systolic blood pressure (SBP) with ASIs compared to placebo, with a mean difference of Mean Difference (MD) -5.44, 95% Confidence Interval (CI) -7.02 to -3.86; p-value <0.00001, I^2 = 26%], indicating effective blood pressure management in older adults with hypertension. Additionally, the analysis showed a significant reduction in plasma aldosterone levels favouring the intervention group (MD=-1.89, 95% CI, P=0.00001, I²=0%). However, there was no statistically significant difference in the incidence of serious adverse events between ASIs and placebo (RR=0.98, 95% CI, P=0.86, I²=0%), suggesting that ASIs are generally safe for use in this population.

ASIs are generally well-tolerated among the studied population. Overall, the findings support the efficacy of ASIs in managing hypertension without a significant increase in adverse events. However, future large scale trials are required to confirm our results and determine the long term benefits and risks of ASI in treatment of hypertension.