Advancing antihypertensive drug development

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Nephrology

Background:

• Hypertension impacts over a billion people globally, causing significant cardiovascular issues.
• Current treatments face challenges like resistance, side effects, and poor adherence, hindering optimal blood pressure control.

Purpose of the Study:

• To review innovative therapeutic strategies for managing hypertension.
• To explore novel approaches addressing treatment resistance, adverse effects, and adherence challenges.

Main Methods:

• Review of emerging pharmacological agents including aldosterone synthase inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists.
• Analysis of novel therapeutic modalities such as RNA-based therapies (e.g., zilebesiran), AT2 receptor agonists, ACE2 activators, and NAD+ boosting compounds.
• Discussion of supportive strategies like gut microbiome modulation and fixed-dose combination pills.

Main Results:

• Aldosterone synthase inhibitors and non-steroidal mineralocorticoid receptor antagonists demonstrate improved blood pressure control with enhanced cardiorenal protection and reduced hyperkalemia risk.
• Endothelin receptor antagonists show potential for treating resistant hypertension by targeting vasoconstriction.
• RNA-based therapies, such as zilebesiran, offer sustained blood pressure reduction via angiotensinogen suppression with infrequent dosing.

Conclusions:

• Emerging therapies target specific pathophysiological pathways for a precision-focused approach to hypertension management.
• Novel strategies promise to improve blood pressure control, reduce the global burden of hypertension, and enhance patient outcomes.
• Future research and clinical application of these innovations are crucial for advancing hypertension care.