The Combination of Beta-Blockers and ACE Inhibitors Across the Spectrum of Cardiovascular Diseases

Abstract

Cardiovascular disease is the leading cause of mortality worldwide, affecting a wide range of patients at different stages across the cardiovascular continuum. Hypertension is one of the earliest risk factors in this continuum and can be controlled in most patients with currently available antihypertensive agents. However, goals are often not met because treatments are not optimized in terms of tailoring therapy to individual patients based on their hypertension subclass and cardiovascular risk profile and initiating early use of adapted-dose, single-pill combinations. In this context, beta-blockers in combination with angiotensin-converting enzyme (ACE) inhibitors are of special interest as a result of their complementary actions on the sympathetic nervous system and renin-angiotensin-aldosterone system, two interlinked pathways that influence cardiovascular risk and disease outcomes. In addition to their antihypertensive actions, beta-blockers are used to manage arrhythmias and treat angina pectoris and heart failure, while ACE inhibitors provide cardioprotection in patients with acute coronary syndromes and treat congestive heart failure. A broad range of patients may therefore receive the combination in routine clinical practice. This paper examines the supporting evidence for beta-blockers and ACE inhibitors in each of the above indications and considers the rationale for combining these agents into a single pill, using data from bisoprolol and perindopril randomized controlled trials as supporting evidence. Combining these established antihypertensive agents into a single pill continues to provide effective blood pressure lowering and improved cardiovascular outcomes while allowing a greater proportion of patients to rapidly achieve treatment targets.

Keywords: Angiotensin II receptor blockers; Angiotensin-converting enzyme inhibitors; Beta-blockers; Coronary artery disease; Hypertension; Renin angiotensin aldosterone system.

Fig. 1

Beta-blocker and ACE inhibitor combination along the cardiovascular continuum (adapted with permission from Dzau and Braunwald, 1991 [104], and Fox, 2007 [105]). ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; BB, beta-blockers; BP, blood pressure; HR, heart rate

Fig. 2

Data from a retrospective pooled analysis of patients from three large perindopril outcome trials (EUROPA, ADVANCE, and PROGRESS) who received perindopril or placebo and were already on beta-blocker therapy. Adding perindopril to a beta-blocker treatment was associated with a decreased risk of the primary composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, and stroke, as well as the secondary endpoints of non-fatal myocardial infarction and all-cause mortality ( reproduced from Brugts et al., 2017 [101] (published under CC-BY license)