Key result
Lorundrostat and baxdrostat show comparable overall SBP reductions, though high-dose baxdrostat lowers pressure ~4 mmHg more.
Why the study?
The aldosterone synthase inhibitors lorundrostat and baxdrostat have each demonstrated significant SBP reductions in placebo-controlled RCTs, but no head-to-head trial comparing them has been conducted.
Does lorundrostat versus baxdrostat improve systolic blood pressure in patients with uncontrolled hypertension?
Meta-Analysis (n=2,599)
Does lorundrostat versus baxdrostat improve systolic blood pressure in patients with uncontrolled hypertension?
In an indirect comparison of five RCTs, the aldosterone synthase inhibitors lorundrostat and baxdrostat demonstrated broadly comparable systolic blood pressure reductions and similarly elevated risks of hyperkalemia in uncontrolled hypertension, with a modest dose-specific advantage for baxdrostat 2 mg over lorundrostat 100 mg.
Answers are grounded in this paper and cite their sources.
Requires vigilant hyperkalemia monitoring with either agent; indirect data leave direct head-to-head trials open.
Background: Aldosterone synthase inhibitors are an emerging class that suppresses aldosterone biosynthesis via CYP11B2 inhibition, offering a mechanistically distinct alternative to mineralocorticoid receptor antagonists. Lorundrostat and baxdrostat have each demonstrated significant systolic blood pressure (SBP) reductions in randomized, placebo-controlled trials (RCTs), but no head-to-head trial has been conducted. Methods: We conducted a placebo-anchored adjusted indirect treatment comparison using the Bucher method within a star-shaped evidence network. The primary efficacy outcome was change in SBP. Safety outcomes were serious adverse events and hyperkalemia. Dose-specific and pooled analyses used a common-effects model with a shared placebo comparator. Results: Five placebo-controlled RCTs ( N = 2599) were included. Both agents significantly reduced SBP at all evaluated doses (all P < 0.0001): lorundrostat −7.87 mmHg at 50 mg and −6.66 mmHg at 100 mg; baxdrostat −8.50 mmHg at 1 mg and −10.22 mmHg at 2 mg. The lower-dose pair was statistically equivalent (lorundrostat 50 mg vs. baxdrostat 1 mg: mean difference (MD), +0.63 mmHg; P = 0.645); baxdrostat 2 mg produced a modest but significant advantage over lorundrostat 100 mg (MD, +3.56 mmHg; P = 0.043). Pooled SBP reductions were −7.64 mmHg and −9.36 mmHg for lorundrostat and baxdrostat, respectively; the pooled indirect comparison was not significant ( P = 0.163). Neither agent increased SAE risk versus placebo. Both agents markedly increased hyperkalemia risk (lorundrostat pooled risk ratio (RR), 8.16; baxdrostat pooled RR, 15.12); the between-drug comparison was not significant. I2 was 0% for SBP and hyperkalemia. Conclusions: Lorundrostat and baxdrostat show broadly comparable antihypertensive efficacy in uncontrolled hypertension; baxdrostat 2 mg produces a modest but statistically significant additional SBP reduction compared with lorundrostat 100 mg in a dose-level indirect comparison. Both agents markedly increase the risk of hyperkalemia versus placebo. Direct head-to-head trials are required to definitively establish comparative efficacy and safety.
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Yousif et al. (2026) conducted a meta-analysis in Uncontrolled hypertension (n=2,599). Lorundrostat vs. Baxdrostat (1 mg, 2 mg) via shared placebo comparator was evaluated on Change in systolic blood pressure (SBP) (MD +3.56 mmHg (baxdrostat 2 mg vs lorundrostat 100 mg), p=0.163). Lorundrostat and baxdrostat showed comparable pooled SBP reductions (−7.64 vs −9.36 mmHg; P=0.163), though baxdrostat 2 mg exceeded lorundrostat 100 mg (MD +3.56 mmHg; P=0.043).
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