New Molecules for Treating Resistant Hypertension: a Clinical Perspective

Area of Science:

• Cardiovascular Pharmacology
• Nephrology
• Clinical Hypertension Research

Background:

• Resistant hypertension (RH) is defined as blood pressure (BP) above target despite adherence to three or more antihypertensive medications, including a diuretic.
• Current RH pharmacological trials primarily evaluate older agents, with spironolactone being the most effective fourth-line option, though its use is limited by side effects and hyperkalemia risk in certain patient groups like those with chronic kidney disease (CKD).

Purpose of the Study:

• To review findings from trials on pharmacological treatments for general and resistant hypertension (RH).
• To propose future research and clinical directions for managing RH.

Main Methods:

• Review of clinical trials evaluating pharmacological treatment approaches for hypertension.
• Identification and discussion of novel molecular targets and agents for RH treatment.

Main Results:

• Existing RH trials have predominantly focused on older antihypertensive medications.
• Spironolactone is currently the most efficacious fourth-line agent for RH but has limitations.
• Numerous novel molecular targets and agents are being investigated for hypertension, with potential applications for RH.

Conclusions:

• There is a significant lack of clinical trial data for newer molecules specifically in the context of RH.
• Emerging novel agents for non-resistant hypertension present opportunities for developing new, effective, and well-tolerated RH treatments.
• Dedicated clinical trials are urgently needed to assess the efficacy and applicability of novel pharmacological agents for resistant hypertension.