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The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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Multiple classes of antihypertensive medications are employed in treating hypertension. The most commonly recommended first-line treatments include:Thiazide Diuretics, such as chlorthalidone, increase sodium and water excretion from the body, reducing blood volume and blood pressure.Angiotensin-converting enzyme inhibitors, like lisinopril, block the conversion of angiotensin I to II, a potent vasoconstrictor lowering blood pressure.Angiotensin II Receptor Blockers (ARBs) prevent angiotensin II...
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Second-Generation Aldosterone Synthase Inhibitors for Hypertension: A Bayesian Meta-Analysis of Randomized Trials.

Flavia Queiroga1, Beatriz Araújo2, André Rivera2

  • 1Division of General Internal Medicine, Department of Medicine, Emory University, Atlanta, Georgia, USA.

JACC. Advances
|February 28, 2026
PubMed
Summary

Second-generation aldosterone-synthase inhibitors (ASIs) effectively lower blood pressure in hypertensive patients. However, these novel treatments increase risks for hyperkalemia, hyponatremia, and hypotension.

Keywords:
aldosteronealdosterone synthase inhibitorschronic kidney diseasehypertension

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Clinical Trials

Background:

  • Second-generation aldosterone-synthase inhibitors (ASIs) represent a potential new therapeutic class for managing hypertension.
  • Understanding the efficacy and safety profile of these agents is crucial for clinical application.

Purpose of the Study:

  • To systematically evaluate the effectiveness and safety of second-generation ASIs in patients diagnosed with hypertension.
  • To synthesize evidence from randomized controlled trials (RCTs) to inform treatment guidelines.

Main Methods:

  • A comprehensive search of major scientific databases was conducted to identify relevant RCTs.
  • Bayesian meta-analysis models were employed to estimate treatment effects for blood pressure reduction and adverse events.
  • The analysis included specific ASIs such as baxdrostat, lorundrostat, and vicadrostat.

Main Results:

  • ASIs demonstrated a significant reduction in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to placebo.
  • While ASIs did not impact all-cause mortality or adrenal insufficiency, they were associated with increased odds of hyperkalemia, hyponatremia, and hypotension.
  • Subgroup analyses indicated a high probability of achieving clinically meaningful SBP reduction with baxdrostat and lorundrostat.

Conclusions:

  • Second-generation ASIs show a high likelihood of achieving clinically significant SBP reduction in hypertensive patients.
  • The use of ASIs is associated with an increased incidence of electrolyte imbalances (hyperkalemia, hyponatremia) and hypotension, necessitating careful patient monitoring.