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Published ahead of print on February 27, 2004, doi:10.1164/rccm.200309-1219OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 9, May 2004, 1041-1045

A more recent version of this article appeared on May 1, 2004
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Submitted on September 5, 2003
Accepted on February 20, 2004

Effects of an Angiotensin Converting Enzyme Inhibitor-based Regimen on Pneumonia Risk

Takayoshi Ohkubo1*, Neil Chapman2, Bruce Neal3, Mark Woodward3, Teruo Omae4, and John Chalmers3

1 Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Science, Tohoku University Hospital, Sendai, Japan, 2 Department of Medicine, St. Mary's Hospital, London, United Kingdom, 3 Institute for International Health, University of Sydney, Sydney, Australia, 4 National Cardiovascular Center, Osaka, Japan

* To whom correspondence should be addressed. E-mail: tohkubo{at}mail.tains.tohoku.ac.jp.

Observational studies conducted among Asian populations suggest that the risk of pneumonia is substantially reduced among users of angiotensin converting enzyme (ACE) inhibitors but not other blood pressure lowering agents. We conducted analyses of the effects of ACE inhibitor therapy on pneumonia in 6105 patients with a history of stroke or transient ischaemic attack enrolled in a randomised trial conducted in Australasia, Europe and Asia. Patients were randomly assigned perindopril-based active treatment or placebo. The effects of ACE inhibitors on pneumonia (fatal or non-fatal) were determined from Cox models fitted according to the principle of intention-to-treat. During a median follow-up of 3.9 years, 261 patients developed pneumonia. Overall, active treatment was associated with a non-significant 19% lower risk of pneumonia (95% CI -3 to 37; p=0.09) compared to placebo. Active treatment significantly reduced the risk of pneumonia among participants of Asian ethnicity [47% (14 to 67%; p=0.01)], with no significant effect among non-Asian participants [5% (-27 to 29%; p=0.7)] (p for homogeneity=0.04). These findings substantially add to the body of evidence about the effects of these drugs on pneumonia but do not provide the definitive information required to inform clinical decisions about the prevention of pneumonia with ACE inhibitors.
Key words: Pneumonia, Angiotensin Converting Enzyme Inhibitor, Angiotensin Converting Enzyme Insertion/Deletion polymorphism, Stroke, Randomized Controlled Trial




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