Who benefits, and how much does it actually lower blood pressure?
The clearest answer: people with resistant or uncontrolled hypertension—those whose blood pressure stays high despite two or more medications—are the main group that appears to benefit. In a meta-analysis of 8 randomized controlled trials, aldosterone synthase inhibitors (ASIs) lowered systolic blood pressure (the top number) by about 8 mmHg more than placebo, and diastolic (bottom number) by about 3.4 mmHg more [1]. That might sound modest, but it's enough to double the likelihood of achieving a systolic target under 130 mmHg [1]—a meaningful step for people stuck on multiple drugs.
The largest single trial in this set, the Target-HTN study, tested the ASI lorundrostat in 200 adults with uncontrolled hypertension on two or more medications. At the 50 mg dose, systolic blood pressure dropped by 9.6 mmHg more than placebo after 8 weeks [2]. Notably, the benefit appeared even in people whose renin levels were not suppressed—a subgroup often thought to be less responsive to aldosterone-targeting drugs [2]. So the effect isn't limited to a narrow biomarker-defined group.
What's the catch? Safety concerns you need to know
The main trade-off is potassium. ASIs block aldosterone, which normally helps the kidneys excrete potassium, so potassium levels can climb. In the meta-analysis, ASIs were associated with a seven-fold higher risk of hyperkalemia (high potassium) compared to placebo [1]. In the lorundrostat trial, six participants (about 3% of those on the drug) had potassium levels above 6.0 mmol/L—a level that can cause dangerous heart rhythms—though all corrected with dose reduction or stopping the drug [2]. This is a real, manageable risk, but it means regular blood tests are essential.
There's also a modest effect on kidney function. The meta-analysis found a small drop in estimated glomerular filtration rate (eGFR, a measure of kidney filtering) of about 6.5 mL/min/1.73m² [1]. That's similar to what's seen with other blood pressure drugs like ACE inhibitors, and it's often a sign of reduced pressure inside the kidney rather than damage, but it still needs monitoring. On the positive side, the meta-analysis found no significant increase in serious adverse events or drug discontinuation compared to placebo [1], and a separate review of lorundrostat trials concluded that while minor side effects like symptomatic hypotension were more common, serious events were not [5].
How does this compare to existing treatments, and what's the bottom line?
ASIs work differently from older drugs like spironolactone, which block the aldosterone receptor. ASIs stop the body from making aldosterone in the first place, which may avoid some of the side effects like breast tenderness and also prevent 'aldosterone escape'—a rebound increase that can limit long-term effectiveness [6]. In chronic kidney disease, one ASI (BI 690517) reduced urine protein by 39% compared to 3% with placebo in a phase 2 trial, suggesting potential kidney benefits beyond blood pressure [3].
But the evidence is still early. Most trials are phase 2, lasting 8–12 weeks, and long-term safety data are limited [3][6]. One real-world study of the older ASI osilodrostat in 80 patients showed blood pressure control improved from 16% at 4 weeks to 60% at 1 year, but serious adverse events rose to 40% at 1 year—though this was a small, retrospective analysis without a control group [4]. So, the bottom line: ASIs are a genuinely promising new tool for difficult-to-control hypertension, with solid short-term efficacy, but they're not yet ready for routine use—they require careful potassium and kidney monitoring, and we need longer-term studies to confirm they're safe and effective over years.
About These Sources
This answer is built on 6 peer-reviewed studies — published from 2023 to 2026, 5 from 2024 or later, 2 in Q1 journals, collectively cited 159 times — selected as the most relevant from 6 studies that passed quality screening, drawn from 40 papers retrieved from a database of over 500 million.
Sources used in this answer
Efficacy of Aldosterone synthase inhibitors in uncontrolled and resistant hypertension: A systematic review and updated meta-analysis with grade assessment.
A meta-analysis of 8 RCTs found ASIs lowered systolic BP by ~8 mmHg and diastolic by ~3.4 mmHg more than placebo, doubled the chance of achieving SBP <130 mmHg, but increased risks of hyperkalemia (7-fold), hyponatremia, and hypotension, with no significant rise in serious adverse events.
Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension
In a randomized, placebo-controlled dose-ranging trial (Target-HTN) of 200 adults with uncontrolled hypertension, lorundrostat 50 mg once daily reduced systolic BP by 9.6 mmHg more than placebo at 8 weeks; 6 participants had potassium >6.0 mmol/L, all corrected with dose adjustment.
Aldosterone Synthase Inhibitors for Treatment of Hypertension and Chronic Kidney Disease
A review of phase 2 trials reported that baxdrostat lowered SBP by 11 mmHg in resistant hypertension, lorundrostat by 9.6 mmHg in uncontrolled hypertension, and BI 690517 reduced albuminuria by 39% in CKD; hyperkalemia occurred in 2.9–14.2% across trials.
Abstract 4357375: Safety and Efficacy of the Aldosterone Synthase Inhibitor Osilodrostat in Primary Hypertension: A Retrospective Cohort Analysis
A retrospective cohort of 80 adults with essential hypertension treated with osilodrostat showed BP control improved from 16% at 4 weeks to 60% at 1 year, but serious adverse events rose to 40% at 1 year; survival was 90.8% at 52 weeks.
Safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, in patients with uncontrolled hypertension: A systematic review and meta-analysis
A meta-analysis of 3 RCTs (1,568 subjects) found lorundrostat 50 mg lowered office systolic BP by 11.11 mmHg and 100 mg lowered 24-hour ambulatory systolic BP by 7.18 mmHg more than placebo, but increased risks of any adverse events and symptomatic hypotension, not serious AEs.
Aldosterone synthase inhibitors in hypertension and chronic kidney disease: double the benefit?
A review concluded that second-generation ASIs (baxdrostat, lorundrostat, vicadrostat) effectively lower BP and albuminuria in hypertension and CKD, with enhanced safety profiles compared to older agents, though long-term outcomes are still under investigation.