RAS inhibitors' dose-dependent efficacy: myth or reality?

Area of Science:

• Cardiology
• Pharmacology
• Hypertension Management

Background:

• Hypertension treatment presents challenges, particularly regarding the appropriate utilization of drug classes.
• The assumption of dose-dependent blood pressure (BP) reduction is not universally applicable to all renin-angiotensin system (RAS) blockers.

Purpose of the Study:

• To review the dose-dependent effects of RAS blockers on BP and cardiovascular protection.
• To evaluate the optimal dosing strategies for RAS blockers in hypertension management.

Main Methods:

• A comprehensive literature search of PubMed and Cochrane databases was conducted.
• Articles focusing on the dose-response relationship of RAS blockers concerning BP and cardiovascular outcomes were analyzed.

Main Results:

• Most angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) exhibit flat dose-response curves for BP reduction; higher doses primarily extend duration, not potency.
• Perindopril is identified as a unique ACE inhibitor with a true dose-response curve for BP reduction.
• RAS blockers' effectiveness in preventing target organ damage is dose-dependent and may be independent of BP control, necessitating full-dose administration for optimal benefit.
• ACE inhibitors, particularly perindopril-based regimens, demonstrate superior outcomes in all-cause mortality compared to ARBs, supported by major clinical trials.

Conclusions:

• A treatment strategy employing ACE inhibitors with dose-dependent efficacy, such as perindopril, offers improved BP control and enhanced protection against target organ damage.
• Optimizing RAS blocker dosage, guided by clinical trial evidence, is crucial for reducing cardiovascular event incidence in hypertensive patients.