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Post-Stroke Pneumonia Prevention by Angiotensin-Converting Enzyme Inhibitors: Results of a Meta-analysis of Five Studies in Asians

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Abstract

Introduction

Angiotensin-converting enzyme inhibitors (ACEIs) are reported to reduce the incidence of aspiration pneumonia in hypertensive patients. In this study, a metaanalysis was conducted to obtain statistically more reliable estimates of outcome.

Methods

The MEDLINE and JMEDICINE databases were searched and the following study selection criteria were applied: (1) comparative controlled studies identified with the following keywords: drug therapy, ACEI, hypertension, swallowing function, dysphagia, stroke, and pneumonia; (2) a minimum follow-up period of 6 months; and (3) a minimum number of patients of more than 100. Patients with hypertension and a history of stroke or transient ischemic attack (TIA) in five controlled studies that reported the incidence of pneumonia were included in the analysis.

Results

A total of 8,693 post-stroke patients were given ACEIs with another antihypertensive agent or placebo as a control. In all studies, ACEIs, particularly imidapril, exhibited preventive effects equating to a relative risk that ranged from 0.32 to 0.81 compared with controls. In the combined studies the overall relative risk of ACEI-treated patients versus controls was 0.61 (95% confidence intervals [CI] 0.51–0.75; P < 0.001). Among Asian patients, the relative risk was 0.42 (95% CI 0.32–0.56; P < 0.001). Among Japanese patients, an even greater preventive effect was found for ACEIs versus other antihypertensives (relative risk: 0.38 [95% CI 0.27-0.54; P < 0.001]).

Conclusion

ACEIs appear to be more effective than other antihypertensive agents or placebo in reducing pneumonia risk in post-stroke patients, especially in Asian populations.

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References

  1. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344:665–671.

    Article  CAS  PubMed  Google Scholar 

  2. Pellegrini CA, DeMeester TR, Johnson LF, Skinner DB. Gastroesophageal reflux and pulmonary aspiration: incidence, functional abnormality and results of surgical therapy. Surgery. 1979;86:110–119.

    CAS  PubMed  Google Scholar 

  3. Loeb MB, Becker M, Eady A, Walker-Dilks C. Interventions to prevent aspiration pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003;51:1018–1022.

    Article  PubMed  Google Scholar 

  4. Doggett DL, Tappe KA, Mitchell MD, Chapell R, Coates V, Turkelson CM. Prevention of pneumonia in elderly stroke patients by systematic diagnosis and treatment of dysphagia: an evidence-based comprehensive analysis of the literature. Dysphagia. 2001;16:279–295.

    Article  CAS  PubMed  Google Scholar 

  5. Katzan IL, Cebul RD, Husak SH, Dawson NV, Baker DW. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology. 2003;60:620–625.

    Article  CAS  PubMed  Google Scholar 

  6. Kimura K, Minematsu K, Kazui S, Yamaguchi T; the Japan Multicenter Stroke Investigators’ Collaboration (J-MUSIC). Mortality and cause of death after hospital discharge in 10,981 patients with ischemic stroke and transient ischemic attack. Cerebrovasc Dis. 2005;19:171–178.

    Article  PubMed  Google Scholar 

  7. Nakagawa T, Wada H, Sekizawa K, Arai H, Sasaki H. Amantadine and pneumonia. Lancet. 1999;353:1157.

    Article  CAS  PubMed  Google Scholar 

  8. Yamaya M, Yanai M, Ohrui T, Arai H, Sekizawa K, Sasaki H. Antithrombotic therapy for prevention of pneumonia. J Am Geriatr Soc. 2001;49:687–688.

    Article  CAS  PubMed  Google Scholar 

  9. Shinohara Y; the CSPS Group. Antiplatelet cilostazol is effective in the prevention of pneumonia in ischemic stroke patients in the chronic stage. Cerebrovasc Dis. 2006;22:57–60.

    Article  CAS  PubMed  Google Scholar 

  10. Arai T, Yoshimi N, Fujiwara H, Fujiwara H, Sekizawa K. Serum substance P concentrations and silent aspiration in elderly patients with stroke. Neurology. 2003;61:1625–1626.

    Article  CAS  PubMed  Google Scholar 

  11. Sekizawa K, Matsui T, Nakagawa T, Nakagawa T, Nakayama K, Sasaki H. ACE inhibitors and pneumonia. Lancet. 1998;352:1069.

    Article  CAS  PubMed  Google Scholar 

  12. Ohkubo T, Chapman N, Neal B, et al; the Perindopril Protection Against Recurrent Stroke Study Collaborative Group. Effects of an angiotensin-converting enzyme inhibitor-based regimen on pneumonia risk. Am J Respir Crit Care Med. 2004;169:1041–1045.

    Article  PubMed  Google Scholar 

  13. Arai T, Yasuda Y, Toshima S, Yoshimi N, Kashiki Y. ACE inhibitors and pneumonia in elderly people. Lancet. 1998;352:1937–1938.

    Article  CAS  PubMed  Google Scholar 

  14. Teramoto S. Novel preventive and therapeutic strategy for post-stroke pneumonia. Expert Rev Neurother. 2009;9:1187–1200.

    Article  PubMed  Google Scholar 

  15. Arai T, Yasuda Y, Takaya T, et al. ACE inhibitors and reduction of the risk of pneumonia in elderly people. Am J Hypertens. 2000;13:1050–1051.

    Article  CAS  PubMed  Google Scholar 

  16. Arai T, Yasuda Y, Takaya T, et al. Angiotensinconverting enzyme inhibitor, angiotensin-II receptor antagonists, and pneumonia in elderly hypertensive patients with stroke. Chest. 2001;119:660–661.

    Article  CAS  PubMed  Google Scholar 

  17. Akutagawa O, Honda K, Sasaki T. A study of prevention of pneumonia development in the elderly by ACE inhibitors. Progr Med. 2002;22:2705–2708. In Japanese.

    Google Scholar 

  18. Arai T, Sekizawa K, Ohrui T, et al. ACE inhibitors and protection against pneumonia in elderly patients with stroke. Neurology. 2005;64:573–574.

    Article  CAS  PubMed  Google Scholar 

  19. Bender R. Calculating confidence intervals for the number needed to treat. Control Clin Trials. 2001;22:102–110.

    Article  CAS  PubMed  Google Scholar 

  20. Davenport RJ, Dennis MS, Wellwood I, Warlow CP. Complications after acute stroke. Stroke. 1996;27:415–420.

    Article  CAS  PubMed  Google Scholar 

  21. Scottish Intercollegiate Guidelines Network. Management of patients with stroke: Identification and management of dysphagia. A national clinical guideline. Edinburgh: Elliott House; 2010.

    Google Scholar 

  22. MacMahon S, Collins R. Reliable assessment of the effects of treatment on mortality and major morbidity, II: Observational studies. Lancet. 2001;357:455–462.

    Article  CAS  PubMed  Google Scholar 

  23. Van de Garde EMW, Souverein PC, Hak E, Deneer VH, van den Bosch JM, Leufkens HG. Angiotensinconverting enzyme inhibitor use and protection against pneumonia in patients with diabetes. J Hypertens. 2007;25:235–239.

    Article  PubMed  Google Scholar 

  24. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: A review of the literature and pathophysiology. Ann Intern Med. 1992;117:234–242.

    CAS  PubMed  Google Scholar 

  25. Nakayama K, Sekizawa K, Sasaki H. ACE inhibitor and swallowing reflex. Chest. 1998;113:1425.

    Article  CAS  PubMed  Google Scholar 

  26. Itoh M, Meguro K, Fujiwara T, et al. Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET. Ann Nucl Med. 1994;8:245–251.

    Article  CAS  PubMed  Google Scholar 

  27. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc. 2001;49:85–90.

    Article  CAS  PubMed  Google Scholar 

  28. Nakagawa T, Ohrui T, Sekizawa K, Sasaki H. Sputum substance P in aspiration pneumonia. Lancet. 1995;345:1447.

    Article  CAS  PubMed  Google Scholar 

  29. Cascieri MA, Bull HG, Mumford RA, Patchett AA, Thornberry NA, Liang T. Carboxyl-terminal tripeptidyl hydrolysis of substance P by purified rabbit lung angiotensin-converting enzyme and the potentiation of substance P activity in vivo by captopril and MK-422. Mol Pharmacol. 1984;25:287–293.

    CAS  PubMed  Google Scholar 

  30. Shore SA, Stimler-Gerard NP, Coats SR, Drazen JM. Substance P-induced bronchoconstriction in the guinea pig. Enhancement by inhibitors of neutral metalloendopeptidase and angiotensin-converting enzyme. Am Rev Respir Dis. 1988;137:331–336.

    CAS  PubMed  Google Scholar 

  31. Sekizawa K, Jia YX, Ebihara T, Hirose Y, Hirayama Y, Sasaki H. Role of substance P in cough. Pulm Pharmacol. 1996;9:323–328.

    Article  CAS  PubMed  Google Scholar 

  32. Medhora M, Gao F, Jacobs ER, Moulder JE. Radiation damage to the lung: mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology. 2012;17:66–71.

    Article  PubMed  Google Scholar 

  33. Woo J, Chan TYK. A high incidence of cough associated with combination therapy of hypertension with isradipine and lisinopril in Chinese subjects. Br J Clin Pract. 1991;45:178–180.

    CAS  PubMed  Google Scholar 

  34. Chan WK, Chan TYK, Luk WK, Leung VK, Li TH, Critchley JA. A high incidence of cough in Chinese subjects treated with angiotensin converting enzyme inhibitors. Eur J Clin Pharmacol. 1993;44:299–300.

    Article  CAS  PubMed  Google Scholar 

  35. Woo KS, Nicholls MG. High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese. Br J Clin Pharmacol. 1995;40:141–144.

    CAS  PubMed  Google Scholar 

  36. Sharpe N; the international HOPE TIPS investigators. The HOPE TIPS: the HOPE study translated into practices. Cardiovasc Drugs Ther. 2005;19:197–201.

    Article  PubMed  Google Scholar 

  37. Morimoto S, Okaishi K, Onishi M, et al. Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients. Am J Med. 2002;112:89–94.

    Article  CAS  PubMed  Google Scholar 

  38. Saruta T, Omae T, Kuramochi M, et al. Imidapril hydrochloride in essential hypertension: a double-blind comparative study using enalapril maleate as a control. J Hypertens. 1995;13(Suppl. 3):S23–S30.

    Article  CAS  Google Scholar 

  39. Ebihara T, Sekizawa K, Nakazawa H, Sasaki H. Capsaicin and swallowing reflex. Lancet. 1993;341:432.

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to Yukito Shinohara.

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Shinohara, Y., Origasa, H. Post-Stroke Pneumonia Prevention by Angiotensin-Converting Enzyme Inhibitors: Results of a Meta-analysis of Five Studies in Asians. Adv Therapy 29, 900–912 (2012). https://doi.org/10.1007/s12325-012-0049-1

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