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Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis

BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e4260 (Published 11 July 2012) Cite this as: BMJ 2012;345:e4260
  1. Daniel Caldeira, cardiologist resident, assistant of clinical pharmacology1,
  2. Joana Alarcão, scientific consultant, assistant of clinical pharmacology2,
  3. António Vaz-Carneiro, clinical professor of medicine, director of the Center for Evidence-Based Medicine23,
  4. João Costa, professor of clinical pharmacology, coordinator of the Portuguese Cochrane Centre123
  1. 1Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon
  2. 2Center for Evidence-Based Medicine, Faculty of Medicine, University of Lisbon, Avenue Professor Egas Moniz, 1649-028, Lisbon, Portugal
  3. 3Cochrane Coordinating Center Portugal, Faculty of Medicine, University of Lisbon
  1. Correspondence to: J Costa jncosta{at}fm.ul.pt
  • Accepted 10 May 2012

Abstract

Objective To systematically review longitudinal studies evaluating use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and risk of pneumonia.

Design Systematic review and meta-analysis.

Data sources Medline through PubMed, Web of Science with conference proceedings (inception to June 2011), and US Food and Drug Administration website (June 2011). Systematic reviews and references of retrieved articles were also searched.

Study selection Two reviewers independently selected randomised controlled trials and cohort and case-control studies evaluating the use of ACE inhibitors or ARBs and risk of pneumonia and retrieved characteristics of the studies and data estimates.

Data synthesis The primary outcome was incidence of pneumonia and the secondary outcome was pneumonia related mortality. Subgroup analyses were carried according to baseline morbidities (stroke, heart failure, and chronic kidney disease) and patients’ characteristics (Asian and non-Asian). Pooled estimates of odds ratios and 95% confidence intervals were derived by random effects meta-analysis. Adjusted frequentist indirect comparisons between ACE inhibitors and ARBs were estimated and combined with direct evidence whenever available. Heterogeneity was assessed using the I2 test.

Results 37 eligible studies were included. ACE inhibitors were associated with a significantly reduced risk of pneumonia compared with control treatment (19 studies: odds ratio 0.66, 95% confidence interval 0.55 to 0.80; I2=79%) and ARBs (combined direct and indirect odds ratio estimate 0.69, 0.56 to 0.85). In patients with stroke, the risk of pneumonia was also lower in those treated with ACE inhibitors compared with control treatment (odds ratio 0.46, 0.34 to 0.62) and ARBs (0.42, 0.22 to 0.80). ACE inhibitors were associated with a significantly reduced risk of pneumonia among Asian patients (0.43, 0.34 to 0.54) compared with non-Asian patients (0.82, 0.67 to 1.00; P<0.001). Compared with control treatments, both ACE inhibitors (seven studies: odds ratio 0.73, 0.58 to 0.92; I2=51%) and ARBs (one randomised controlled trial: 0.63, 0.40 to 1.00) were associated with a decrease in pneumonia related mortality, without differences between interventions.

Conclusions The best evidence available points towards a putative protective role of ACE inhibitors but not ARBs in risk of pneumonia. Patient populations that may benefit most are those with previous stroke and Asian patients. ACE inhibitors were also associated with a decrease in pneumonia related mortality, but the data lacked strength.

Footnotes

  • We thank the Cochrane Coordinating Centre in Portugal.

  • Contributors: DC and JA contributed to the concept and design, data acquisition, data analysis, and interpretation of the data; wrote the first draft of the manuscript; critically revised the manuscript; and gave final approval of the submitted manuscript. AVC contributed to the interpretation of data, critically revised the manuscript, and gave final approval of the submitted manuscript. JC contributed to the concept and design, data analysis, and interpretation of the data; wrote the first draft of the manuscript; critically revised the manuscript; and gave final approval of the submitted manuscript. JC is the guarantor.

  • Funding: This was an academic project not funded by government or non-government grants.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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