September 5, 2023Open Access

The Pivotal Role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Hypertension Management and Cardiovascular and Renal Protection: A Critical Appraisal and Comparison of International Guidelines

Structured PICO

Do ACE inhibitors and ARBs have equivalent efficacy for cardiovascular and renal protection in patients with hypertension and cardiovascular comorbidities?

Population

Hypertensive patients, often with cardiovascular comorbidities including chronic kidney disease, diabetes, heart failure, peripheral artery disease, atrial fibrillation, or coronary artery disease.

Intervention

Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs)

Comparator

Placebo or active comparators (including direct comparisons between ACEis and ARBs)

Outcome

Cardiovascular and renal outcomes, including all-cause mortality, cardiovascular mortality, and myocardial infarctionhard clinical

While guidelines often consider ACEis and ARBs as equivalent options for hypertension, clinical evidence suggests ACEis may offer superior cardiovascular mortality benefits, potentially due to distinct bradykinin-mediated mechanisms.

Abstract

Arterial hypertension is the main preventable cause of premature mortality worldwide. Across Latin America, hypertension has an estimated prevalence of 25.5-52.5%, although many hypertensive patients remain untreated. Appropriate treatment, started early and continued for the remaining lifespan, significantly reduces the risk of complications and mortality. All international and most regional guidelines emphasize a central role for renin-angiotensin-aldosterone system inhibitors (RAASis) in antihypertensive treatment. The two main RAASi options are angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Although equivalent in terms of blood pressure reduction, ACEis are preferably recommended by some guidelines to manage other cardiovascular comorbidities, with ARBs considered as an alternative when ACEis are not tolerated. This review summarizes the differences between ACEis and ARBs and their place in the international guidelines. It provides a critical appraisal of the guidelines based on available evidence from randomized controlled trials (RCTs) and meta-analyses, especially considering that hypertensive patients in daily practice often have other comorbidities. The observed differences in cardiovascular and renal outcomes in RCTs may be attributed to the different mechanisms of action of ACEis and ARBs, including increased bradykinin levels, potentiated bradykinin response, and stimulated nitric oxide production with ACEis. It may therefore be appropriate to consider ACEis and ARBs as different antihypertensive drugs classes within the same RAASi group. Although guideline recommendations only differentiate between ACEis and ARBs in patients with cardiovascular comorbidities, clinical evidence suggests that ACEis provide benefits in many hypertensive patients, as well as those with other cardiovascular conditions.

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