ACE inhibitors prevent aspiration pneumonia in Asian, but not Caucasian, elderly patients with stroke

To the Editors:

In a recent issue of the European Respiratory Journal, van de Garde et al. 1 demonstrated that the use of angiotensin-converting enzyme (ACE) inhibitors is not associated with a decreased risk of hospitalisation for community-acquired pneumonia (CAP) in a general, essentially white population. Their conclusion that the beneficial effect of ACE inhibitors on pneumonia risk is not observed in a general white population is in contrast with previous findings in Asian populations 1. This was an excellent good study examining the association of ACE inhibitor treatment of cardiovascular disease with a risk reduction of CAP using a large sample size. The results are acceptable and not surprising; however, the discussion and conclusion are misleading.

As shown in table 1⇓, there are controversies regarding the ACE inhibitor effects on the risk reduction of pneumonia even in Asian countries; furthermore, the study samples are very different among the studies. In a prospective study by Sekizawa et al. 2, ACE inhibitor use reduced pneumonia incidence for 2 yrs. They did not examine the general population; subjects were hypertensive elderly patients with a history of stroke or lacuna infarction, and a mean age 10 yrs older than that of the study by van de Garde et al. 1. However, the study by Arai et al. 3 examined the association of ACE inhibitors and the risk reduction of pneumonia in the general hypertensive elderly without stroke in Japan 3. Surprisingly, they had an 8.3–8.9% incidence of pneumonia over 3 yrs, an incidence twenty times higher than the previous data 6, 7. It is hard to believe that ∼3% of hypertensive elderly outpatients without major complications suffered from pneumonia. We have previously presented data showing no association of ACE inhibitor use with pneumonia risk in elderly hypertensive subjects without stroke history 4. Since ACE inhibitors, through the inactivation substance P, improve upper airway reflexes such as swallowing and cough, resulting in the reduction of aspiration pneumonia in elderly patients, they may not reduce the CAP in those patients without deglutition problems. Current evidence indicates that ACE inhibitors play a significant role in the prevention of aspiration pneumonia in the elderly, but not in common CAP in healthy adults. This was confirmed by the sub-analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Ohkubo et al. 5 re-analysed the PROGRESS data concerning the incidence of pneumonia. ACE inhibitor-active treatment significantly reduced the risk of pneumonia among participants of Asian ethnicity (mean (95% confidence interval) 47% (14–67%), p = 0.01), with no significant effect among non-Asian participants (5% (-27–29%), p = 0.7; p for homogeneity = 0.04). These findings add to the body of evidence regarding the effects of these drugs on pneumonia. The randomised design of PROGRESS greatly reduced the likelihood of confounding of the analyses and provided an excellent opportunity to explore the validity of the associations reported in observational studies 2, 3. Thus, the key issue is the selection of elderly subjects in terms of ethnicity, post-stroke state, performance status, type of ACE inhibitor and swallowing function.

The clinical epidemiology research group of Etminan et al. 8 recently reported that no association was found between the use of ACE inhibitors or angiotensin II receptor blockers (ARBs) and risk of hospitalisation secondary to CAP. The study further confirmed the limited efficacy of ACE inhibitors on the risk reduction of hospitalisation due to pneumonia in a white population. As we speculated, ARBs did not have any role in the prevention of aspiration pneumonia.

Stroke and post-stroke patients often exhibit a normal cough reflex, but not swallowing reflex, and the small volume of aspirated materials due to impaired swallowing during night is a key factor for the risk of pneumonia 9, 10. Hence, a ten times higher rate of pneumonia in post-stroke patients without significant neurological deficit, compared with the rate of pneumonia in normal elderly 5. Furthermore, the age-dependent impairment of upper airway reflexes should be carefully considered for the mechanism of CAP in the elderly irrespective of the history of stroke.

Finally, we emphasise that aspiration and silent aspiration are very important mechanisms of aspiration pneumonia. Silent aspiration is very common in patients with stroke and frail elderly patients, and nasogastric tube feeding without swallowing rehabilitation or oral care cannot reduce the pneumonia risk in patients with swallowing disorders 11.

We believe that angiotensin-converting enzyme inhibitors could prevent aspiration pneumonia in selected elderly patients. Post-stroke and the frail elderly are the best candidates for the pneumonia risk reduction by angiotensin-converting enzyme inhibitors 12. However, these merits may not be consistently observed in Caucasian elderly patients with or without stroke.