Lorundrostat and Baxdrostat significantly reduced systolic blood pressure compared with placebo (MD -7.51 mmHg and -8.63 mmHg, respectively) but increased the risk of hyperkalemia.
Meta-Analysis (n=3,051)
Do selective aldosterone synthase inhibitors (Lorundrostat or Baxdrostat) reduce systolic blood pressure in adults with uncontrolled or resistant hypertension?
Selective aldosterone synthase inhibitors effectively lower systolic blood pressure in uncontrolled or resistant hypertension but carry a significant risk of hyperkalemia.
Mean Difference: -7.51 (95% CI -10.3–-4.71)
Background Aldosterone excess contributes to uncontrolled and resistant hypertension, making aldosterone synthase inhibition a promising therapeutic strategy. Recent randomized trials have evaluated the selective aldosterone synthase inhibitors Lorundrostat and Baxdrostat; however, their efficacy and safety have not been comprehensively synthesized. Methods PubMed, Embase, and Cochrane CENTRAL were searched from inception through April 2026 for randomized controlled trials evaluating Lorundrostat or Baxdrostat in adults with uncontrolled or resistant hypertension. The primary efficacy outcome was placebo-adjusted change in systolic blood pressure (SBP). Safety outcomes included hyperkalemia, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs). Drug-specific pooled analyses were performed using random-effects models. Results Three randomized trials of Lorundrostat (n=1,568) demonstrated a significant reduction in SBP compared with placebo (mean difference MD, -7.51 mmHg; 95% CI, -10.30 to -4.71; I 2 = 0%). Lorundrostat increased the risks of hyperkalemia (RR, 8.06; 95% CI, 2.92–22.27) and TEAEs (RR, 1.45; 95% CI, 1.27–1.66), without a significant increase in SAEs. Three placebo-controlled Baxdrostat trials (n = 1,483) also demonstrated significant reductions in office SBP (MD, -8.63 mmHg; 95% CI, -11.30 to -5.96; I 2 = 0%). Baxdrostat increased the risk of hyperkalemia (RR, 3.81; 95% CI, 1.82–7.97) but was not associated with significant increases in TEAEs or SAEs. Conclusions Selective aldosterone synthase inhibition with Lorundrostat and Baxdrostat produced clinically meaningful reductions in SBP in patients with uncontrolled or resistant hypertension. Hyperkalemia emerged as the principal safety concern, whereas serious adverse events were not significantly increased. Larger and longer-term studies are needed to define long-term safety and cardiovascular outcomes.
Pandey et al. (Wed,) conducted a meta-analysis in Uncontrolled and resistant hypertension (n=3,051). Lorundrostat and Baxdrostat vs. Placebo was evaluated on Placebo-adjusted change in systolic blood pressure (SBP) (MD -7.51, 95% CI -10.30 to -4.71). Lorundrostat and Baxdrostat significantly reduced systolic blood pressure compared with placebo (MD -7.51 mmHg and -8.63 mmHg, respectively) but increased the risk of hyperkalemia.