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Hypertension and Lorundrostat: Key Discoveries From the TARGET-HTN Trial
Hamza Irfan1, Aliza Ahmed2, Komal Devi Nawani3
1Department of Cardiology, Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College Lahore, Lahore, Punjab, Pakistan.
Insights
The Target-HTN trial shows lorundrostat effectively lowers systolic blood pressure in hypertensive patients with specific hormonal profiles. Further Phase 3 trials are recommended for this promising aldosterone synthase inhibitor.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Hypertension is a global health issue, increasing cardiovascular disease (CVD) risk and mortality.
- Prevalence is rising due to aging populations and lifestyle factors, affecting one in three adults globally.
- Aldosterone plays a key role in blood pressure regulation, making its inhibition a therapeutic target.
Purpose of the Study:
- To evaluate the efficacy of lorundrostat, an aldosterone synthase inhibitor, in reducing systolic blood pressure.
- To assess lorundrostat's effect in hypertensive patients, particularly those with suppressed renin and elevated aldosterone.
- To provide data supporting the progression to Phase 3 clinical trials.
Main Methods:
- The Target-HTN trial enrolled patients with hypertension in two cohorts.
- Cohort 1 investigated daily doses of 50 mg and 100 mg lorundrostat versus placebo.
- Cohort 2 explored the 100 mg daily dose in an exploratory analysis.
Main Results:
- Lorundrostat (100 mg and 50 mg daily) significantly reduced systolic blood pressure in Cohort 1 compared to placebo.
- A notable reduction in systolic blood pressure was also observed in Cohort 2 with 100 mg daily lorundrostat.
- These results indicate lorundrostat's potential in managing specific hypertensive patient subgroups.
Conclusions:
- Lorundrostat demonstrates promise as a novel treatment for hypertension, especially in patients with suppressed plasma renin activity and elevated aldosterone.
- The aldosterone synthase inhibitor offers a new therapeutic avenue for blood pressure management.
- Phase 3 trials are warranted to confirm lorundrostat's safety and efficacy in a broader population.
Abstract:
Hypertension, characterized by persistent high blood pressure levels, is a major global health concern, contributing significantly to the risk of cardiovascular diseases (CVD) and overall mortality. It is classified into primary and secondary hypertension, with its prevalence steadily increasing due to ageing populations and unhealthy lifestyle factors. The World Health Organization (WHO) reports a staggering rise in hypertension cases, affecting one in 3 adults worldwide, doubling from 1990 to 2019. A significant development in the field of hypertension treatment is the Target-HTN trial, which investigated the efficacy of lorundrostat, an aldosterone synthase inhibitor, in reducing systolic blood pressure. This trial involved 2 cohorts. Cohort 1, comprising patients with suppressed plasma renin activity and elevated serum aldosterone levels, showed promising results. Lorundrostat doses of 100 mg and 50 mg administered once daily led to substantial reductions in systolic blood pressure compared to a placebo group. Cohort 2, although considered exploratory, also exhibited a notable reduction in systolic blood pressure with a 100 mg once-daily dose of lorundrostat. In conclusion, the Target-HTN trial has demonstrated that lorundrostat, an aldosterone synthase inhibitor, holds promise as an innovative therapeutic approach for reducing systolic blood pressure, especially in hypertensive patients with suppressed plasma renin activity and elevated serum aldosterone levels. These findings advocate for the initiation of Phase 3 trials to further validate the safety and efficacy of lorundrostat in a larger and more diverse patient population.
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