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Adverse Effects of Angiotensin-Converting Enzyme Inhibitors in Humans: A Systematic Review and Meta-Analysis of 378 Randomized Controlled Trials

Author

Listed:
  • Mingkwan Na Takuathung

    (Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
    Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
    These authors contributed equally to this work.)

  • Wannachai Sakuludomkan

    (Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
    Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
    These authors contributed equally to this work.)

  • Rapheephorn Khatsri

    (Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Nahathai Dukaew

    (Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Napatsorn Kraivisitkul

    (Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Balqis Ahmadmusa

    (Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Chollada Mahakkanukrauh

    (Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Kachathip Wangthaweesap

    (Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Jirakit Onin

    (Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Salin Srichai

    (Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Nida Buawangpong

    (Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand)

  • Nut Koonrungsesomboon

    (Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
    Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
    Musculoskeletal Science and Translational Research Center, Chiang Mai University, Chiang Mai 50200, Thailand)

Abstract

Background: Although angiotensin-converting enzyme (ACE) inhibitors are among the most-prescribed medications in the world, the extent to which they increase the risk of adverse effects remains uncertain. This study aimed to systematically determine the adverse effects of ACE inhibitors versus placebo across a wide range of therapeutic settings. Methods: Systematic searches were conducted on PubMed, Web of Science, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing an ACE inhibitor to a placebo were retrieved. The relative risk (RR) and its 95% confidence interval (95% CI) were utilized as a summary effect measure. A random-effects model was used to calculate pooled-effect estimates. Results: A total of 378 RCTs fulfilled the eligibility criteria, with 257 RCTs included in the meta-analysis. Compared with a placebo, ACE inhibitors were associated with an significantly increased risk of dry cough (RR = 2.66, 95% CI = 2.20 to 3.20, p < 0.001), hypotension (RR = 1.98, 95% CI = 1.66 to 2.35, p < 0.001), dizziness (RR = 1.46, 95% CI = 1.26 to 1.70, p < 0.001), and hyperkalemia (RR = 1.24, 95% CI = 1.01 to 1.52, p = 0.037). The risk difference was quantified to be 0.037, 0.030, 0.017, and 0.009, respectively. Conclusions: We quantified the relative risk of numerous adverse events associated with the use of ACE inhibitors in a variety of demographics. This information can help healthcare providers be fully informed about any potential adverse consequences and make appropriate suggestions for their patients requiring ACE inhibitor therapy.

Suggested Citation

  • Mingkwan Na Takuathung & Wannachai Sakuludomkan & Rapheephorn Khatsri & Nahathai Dukaew & Napatsorn Kraivisitkul & Balqis Ahmadmusa & Chollada Mahakkanukrauh & Kachathip Wangthaweesap & Jirakit Onin &, 2022. "Adverse Effects of Angiotensin-Converting Enzyme Inhibitors in Humans: A Systematic Review and Meta-Analysis of 378 Randomized Controlled Trials," IJERPH, MDPI, vol. 19(14), pages 1-13, July.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:14:p:8373-:d:858715
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    References listed on IDEAS

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    1. Su Golder & Yoon K Loke & Martin Bland, 2011. "Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview," PLOS Medicine, Public Library of Science, vol. 8(5), pages 1-13, May.
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    1. Marina Lleal & Marisa Baré & Sara Ortonobes & Daniel Sevilla-Sánchez & Rosa Jordana & Susana Herranz & Maria Queralt Gorgas & Mariona Espaulella-Ferrer & Marta Arellano & Marta de Antonio & Gloria Jul, 2022. "Comprehensive Multimorbidity Patterns in Older Patients Are Associated with Quality Indicators of Medication—MoPIM Cohort Study," IJERPH, MDPI, vol. 19(23), pages 1-16, November.

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