Acid-suppressive
medication use in acute
stroke patients: is it
time to change practice?
Dear editor,
Previous studies have shown that use
of acid-suppressive medications may be
associated with an increased risk of both
community- and hospital-acquired pneu-
monia (HAP) (1). Stroke patients are par-
ticularly at high risk for HAP because of
stroke-associated deficits such as somno-
lence and dysphagia. Two studies from
China reported an increased risk of HAP
in stroke patients who were given proton-
pump inhibitors (2) and histamine-2
receptor antagonists (3). Recently, Herzig
et al. showed an increased risk for
nosocomial pneumonia in hospitalized
stroke patients who were treated with
acid-suppressive medications (4). Signifi-
cantly, after adjusting for 30 covariates,
the odds ratio of HAP in the exposed
group was 2·3 [95% confidence interval
(CI) = 1·2–4·6]. The authors concluded
that acid-suppressive medication use was
associated with more than double the
odds of HAP in patients presenting with
acute stroke and recommended more
restrictive use of these medications.
At our institution, acid-suppressive
medications are commonly used in
hospitalized patients who present with
acute stroke. After obtaining institutional
review board approval, we reviewed 2357
patients who presented with acute stroke
from November 1, 2012 to November 1,
2014. We excluded 382 patients for the
following reasons: (1) acute stroke did not
occur; (2) stroke occurred after hospital-
ization; (3) pneumonia was present on
admission; and (4) admissions < 48 h in
duration. Among the remaining 1975
patients, there were 1335 acute ischemic
stroke and 640 intracranial haemor-
rhage (ICH). Acid-suppressive medica-
tions were used in 1151 (58%). Only
proton-pump inhibitors were used. Acid-
suppressive medications were more likely
to be used in patients with ICH than those
with acute ischemic stroke (84% vs.
46%, P < 0·0001). There were 218 cases of
HAP (11%) and 128 cases of community-
acquired pneumonia (6·5%). The inci-
dence of HAP was higher in those with
ICH than those with acute ischemic
stroke (17% vs. 8%, P < 0·0001). The
odds ratio of developing HAP in patients
who were given acid-suppressive medica-
tions was 4·11 (95% CI = 2·84–5·95)
for the entire cohort, 2·93 (95% CI =
1·91–4·47) for those with acute ischemic
stroke, and 8·40 (95% CI = 2·61–27·00)
for those with ICH. There were 16 cases of
acute gastritis and 7 cases of gastrointes-
tinal haemorrhage that were diag-
nosed during the same hospitalization as
the stroke episode. Acid-suppressive
medications were used in all of these
cases.
In conclusion, we found an increased
risk of HAP in patients with acute stroke,
especially those with ICH. Future studies
should include data on nasogastric or
feeding tube usage, head of bed elevation,
duration of treatment, oral vs. intrave-
nous usage, dose of the medication used,
clear documentation of the sequence
of events, and a quantitative measure of
the benefits conferred by acid-suppressive
medication usage. We propose a double-
blind randomized controlled trial to
ascertain the impact of acid-suppressive
medication use on the development
of HAP.
Zhi-li Wang
1
, Harrison X. Bai
2
,
Xue Gao
3
, Dongxv Qiu
1
, and
Li Yang
1
*
1
Department of Neurology, The Second
Xiangya Hospital, Central South University,
Changsha, Hunan, China
2
Department of Radiology, Hospital of the
University of Pennsylvania, Philadelphia, PA,
USA
3
Department of Neurology, Xiangya Hospital,
Central South University, Changsha, Hunan,
China
References
1 Eom CS, Jeon CY, Lim JW et al. Use of acid-
suppressive drugs and risk of pneumonia: a
systematic review and meta-analysis. CMAJ
2011; 183:310–9.
2 Ran L, Khatibi NH, Qin X et al. Proton
pump inhibitor prophylaxis increases the
risk of nosocomial pneumonia in patients
with an intracerebral hemorrhagic stroke.
Acta Neurochir Suppl 2011; 111:435–9.
3 Sui R, Zhang L. Risk factors of stroke-
associated pneumonia in Chinese patients.
Neurol Res 2011; 33:508–13.
4 Herzig SJ, Doughty C, Lahoti S et al. Acid-
suppressive medication use in acute stroke
and hospital-acquired pneumonia. Ann
Neurol 2014; 76:712–8.
Correspondence: Li Yang*, Department of
Neurology, The Second Xiangya Hospital of
Central South University, 139 Renmin Middle
Road, Changsha, Hunan 410011, China.
E-mail: yangli762@gmail.com
Conflict of interest: None declared.
Funding: This work was supported by the
Natural Science Foundation of China (grant
number 81301988) to Li Yang and China
Ministry of Education Doctoral Program Spot
Foundation (grant number 20130162120061)
to Li Yang.
DOI: 10.1111/ijs.12522
Letter to the editor
© 2015 World Stroke Organization
Vol 10, August 2015, E55 E55