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

Cardiovasc Drugs Ther. 2023 Aug;37(4):757-770. doi: 10.1007/s10557-021-07248-1. Epub 2021 Sep 17.


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.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Antihypertensive Agents / adverse effects
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Heart Failure* / drug therapy
  • Humans
  • Hypertension* / diagnosis
  • Hypertension* / drug therapy
  • Renin-Angiotensin System


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists