Angiotensin-converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: A systematic review, and network meta-analysis

J Clin Hypertens (Greenwich). 2023 Aug;25(8):661-688. doi: 10.1111/jch.14695. Epub 2023 Jul 7.

Abstract

Studies have shown that angiotensin converting enzyme inhibitors (ACEIs) are superior in primary and secondary prevention for cardiac mortality and morbidity to angiotensin receptor blocker (ARBs). One of the common side effects from ACEI is dry cough. The aims of this systematic review, and network meta-analysis are to rank the risk of cough induced by different ACEIs and between ACEI and placebo, ARB or calcium channel blockers (CCB). We performed a systematic review, and network meta-analysis of randomized controlled trials to rank the risk of cough induced by each ACEI and between ACEI and placebo, ARB or CCB. A total of 135 RCTs with 45,420 patients treated with eleven ACEIs were included in the analyses. The pooled estimated relative risk (RR) between ACEI and placebo was 2.21 (95% CI: 2.05-2.39). ACEI had more incidences of cough than ARB (RR 3.2; 95% CI: 2.91, 3.51), and pooled estimated of RR between ACEI and CCB was 5.30 (95% CI: 4.32-6.50) Moexipril ranked as number one for inducing cough (SUCRA 80.4%) and spirapril ranked the least (SUCRA 12.3%). The order for the rest of the ACEIs are as follows: ramipril (SUCRA 76.4%), fosinopril (SUCRA 72.5%), lisinopril (SUCRA 64.7%), benazepril (SUCRA 58.6%), quinapril (SUCRA 56.5%), perindopril (SUCRA 54.1%), enalapril (SUCRA 49.7%), trandolapril (SUCRA 44.6%) and, captopril (SUCRA 13.7%). All ACEI has the similar risk of developing a cough. ACEI should be avoided in patients who have risk of developing cough, and an ARB or CCB is an alternative based on the patient's comorbidity.

Keywords: ACE inhibitors; angiotensin receptor blocker; calcium channel blockers; network meta-analysis.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents* / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Cough / chemically induced
  • Cough / drug therapy
  • Cough / epidemiology
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / epidemiology
  • Network Meta-Analysis

Substances

  • Antihypertensive Agents
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Calcium Channel Blockers