Optimal Dose of Lorundrostat in Uncontrolled Hypertension: A Dose Response Meta-Analysis

Figures

• 

  Figure 1.. Prisma flowsheet

• 

  Figure 2.. Forest plots of: (A) “Change in Systolic BP at 4-6 weeks”; and (B) “Change in Systolic BP in Lorundrostat-treated Patients versus Placebo at 12 weeks” using the mean difference (MD)

• 

  Figure 3.. Forest plots of: (A) “Change in Diastolic BP”; (B) “Change in Serum Aldosterone Levels”; and (C) “Change in Serum Renin Levels” in Lorundrostat-treated Patients versus Placebo using the mean difference (MD)

• 

  Figure 4.. Forest plot of the Pooled Relative Risk (RR) for Serious Adverse Events in Lorundrostat-treated Patients versus Placebo

• 

  Figure 5.. Forest plot of the Pooled Relative Risk (RR) for Incidence of Hyperkalaemia in Lorundrostat-treated Patients versus Placebo

• 

  Figure 6.. Forest plot of the pooled relative risk (RR) for incidence of hyponatremia in lorundrostat-treated patients versus placebo

• 

  Figure 7.. Forest Plot of Sub-groups Analysis of Change in Systolic BP of Patients taking two Hypertensive Medications and three Hypertensive Medications at Baseline

• 

  Figure 8.. Pooled Dose-Response Association between Lorundrostat and mean change in Systolic Blood Pressure (SBP). Lorundrostat Dosage was modelled with restricted cubic splines in a random-effects model. Dash lines represent the 95 % confidence intervals. The dose corresponding to the maximum predicted effect (Xmax) was 56.6 mg/day, at which the estimated maximum MD in systolic BP was -10.52 (95% CI: -13.69 to -7.34). The doses required to achieve 50% and 80% of this maximum predicted effect were ED50 = 19.9 mg/day and ED80 = 33.3 mg/day, respectively. Complete predicted dose–response estimates are presented in Table 2

• 

  Figure 9.. Pooled Dose-Response Association between Lorundrostat and mean change in Diastolic Blood Pressure (DBP). Lorundrostat dosage was modelled with restricted cubic splines in a random-effects model, the EDmax at 54.2mg/day. Dash lines represent the 95 % confidence intervals for the spline model

• 

  Figure 10.. Pooled Dose-Response Association between Lorundrostat and mean change in Serum Aldosterone Levels. Lorundrostat dosage was modelled with restricted cubic splines in a random-effects model. Dash lines represent the 95 % confidence intervals for the spline model. From the pooled spline prediction function, the dose associated with the maximum estimated reduction in aldosterone levels (EDmax) was 70.3 mg/day, corresponding to a mean difference of –4.45 (95% CI: –7.2 to –1.7). The doses required to achieve 50% and 80% of this maximum predicted effect were ED50 = 22.1 mg/day and ED80 = 37.8 mg/day, respectively. Complete predicted dose–response estimates are presented in Table 2

• 

  Figure 11.. Traffic light plot summarizing the risk of bias assessment for individual studies, evaluated using the Cochrane RoB 2.0 tool across five domains: selection bias, performance bias, detection bias, attrition bias, and reporting bias

• 

  Figure 12.. Summary plot of the risk of bias for included studies, showing an overall assessment of studies with “low risk,” “some concerns,” or “high risk” of bias