Hypertension, or high blood pressure, is a major global health concern, affecting millions of people worldwide. Despite the availability of various antihypertensive medications, many patients still struggle to achieve adequate blood pressure control. However, a recent phase II dose-finding trial has shown promising results for a new treatment option. The study investigated the efficacy and safety of a highly selective aldosterone synthase inhibitor known as lorundrostat in patients with uncontrolled hypertension. The findings suggest that lorundrostat may significantly reduce blood pressure levels, particularly in individuals with suppressed renin or obesity.
The Potential of Aldosterone Synthase Inhibitors
Aldosterone synthase inhibitors like lorundrostat are being developed to target the excess aldosterone synthesis that contributes to high blood pressure. This new class of drugs holds significant importance because no novel blood pressure-lowering medications have been introduced in recent years. Patients with obesity and diabetes, in particular, struggle to control their blood pressure, making new treatment options valuable. While mineralocorticoid receptor antagonists like spironolactone have been used to lower blood pressure, aldosterone synthase inhibitors offer a more targeted approach without hormonal adverse effects.
Positive Results in the Trial
The Target-HTN trial, conducted at multiple sites in the U.S., enrolled hypertensive patients with suppressed renin and elevated plasma aldosterone levels. The participants were randomized to receive either lorundrostat or a placebo. The trial results indicated that lorundrostat treatment led to significant reductions in systolic blood pressure. At 8 weeks, patients receiving lorundrostat showed systolic blood pressure reductions of up to 14.1 mm Hg, compared to a 4 mm Hg reduction in the placebo group. Notably, even patients without suppressed renin experienced an 11.4 mm Hg decrease in systolic blood pressure with lorundrostat treatment.
Impact on Obesity-Associated Hypertension
The subgroup analysis of the trial data revealed that individuals with obesity derived the greatest benefit from lorundrostat treatment. Obesity is a known risk factor for hypertension, and targeting aldosterone synthesis in this population may lead to more effective blood pressure control. The findings of this study provide encouraging results for patients with obesity-associated hypertension, who often struggle to achieve adequate blood pressure reduction with existing therapies.
The trial results also indicated that lorundrostat was well-tolerated among the study participants. The reported adverse events were mild, with small expected increases in serum potassium levels and declines in estimated glomerular filtration rate (eGFR). These changes suggest a favorable safety profile for lorundrostat, particularly with the 50 mg once-daily dose. Importantly, there were no significant hormonal adverse effects, such as cortisol insufficiency, observed with lorundrostat treatment.
The promising results from the Target-HTN trial provide a strong rationale for further investigation into the use of lorundrostat as a treatment for uncontrolled hypertension. The ongoing ADVANCE-HTN pivotal trial is currently evaluating lorundrostat as an add-on therapy for patients with uncontrolled or resistant hypertension. Additionally, plans for a larger phase III trial are underway, which will provide more comprehensive data on the efficacy and safety of lorundrostat. If these future studies confirm the findings of the phase II trial, lorundrostat could offer a new and valuable treatment option for patients with hypertension, particularly those with obesity-associated hypertension.
The development of aldosterone synthase inhibitors like lorundrostat represents an important milestone in the treatment of hypertension. The phase II trial results suggest that lorundrostat may effectively reduce blood pressure levels, especially in individuals with suppressed renin or obesity. With its potential for better-targeted treatment and favorable safety profile, lorundrostat offers hope for patients who struggle to achieve blood pressure control. Further studies are required to confirm these findings and establish the long-term efficacy and safety of lorundrostat. Nevertheless, the results of this trial provide a stepping stone towards the development of novel treatment options for uncontrolled hypertension.
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