The association of aspirin use with severity of acute
exacerbation of chronic obstructive pulmonary disease: a
retrospective cohort study
, Mohammad Kamal Faridi
, Carlos A. Camargo
and Kohei Hasegawa
Little is known about the effect of long-term aspirin use on acute severity of COPD. We hypothesized that, in patients hospitalized
for acute exacerbation of COPD (AECOPD), long-term aspirin use is associated with lower risks of disease severity (in-hospital death,
mechanical ventilation use, and hospital length-of-stay). We conducted a retrospective cohort study using large population-based
data from 2012 through 2013. Among 206,686 patients (aged ≥40 years) hospitalized for AECOPD, aspirin users had lower in-
hospital mortality (1.0 vs. 1.4%; OR 0.60 [95% CI 0.50–0.72]; P < 0.001) and lower risk of invasive mechanical ventilation use (1.7 vs.
2.6%; OR 0.64 [95% CI 0.55–0.73]; P < 0.001) compared to non-users, while there was no signiﬁcant difference in risks of non-
invasive positive pressure ventilation use. Length-of-stay was shorter in aspirin users compared to non-users (P < 0.001). In sum, in
patients with AECOPD, aspirin use was associated with lower rates of in-hospital mortality and invasive mechanical ventilation use,
and shorter length-of-stay.
npj Primary Care Respiratory Medicine (2018) 28:7 ; doi:10.1038/s41533-018-0074-x
Increasing evidence suggests a potential beneﬁt of antiplatelet
therapy on chronic outcomes in patients with chronic obstructive
pulmonary disease (COPD).
For example, a recent analysis of an
ongoing prospective cohort study revealed that antiplatelet
therapy was associated with a lower 1-year mortality among
individuals with COPD.
However, little is known about the effect
of aspirin use on acute outcomes (including mortality) in patients
hospitalized for acute exacerbation of COPD (AECOPD).
To examine the association of aspirin use with severity of
AECOPD, we conducted a retrospective cohort study using data
from the State Inpatient Databases (SID) of seven US states
(Arkansas, Florida, Iowa, Nebraska, New York, Utah, and Washing-
ton) from 2012 and 2013. Additional details of the SID may be
The institutional review board of Massachusetts
General Hospital approved this study.
We identiﬁed all hospitalizations made by patients aged ≥40
years with a primary discharge diagnosis of COPD (ICD-9-CM
codes: 491.21, 491.22, 491.8, 491.9, 492.8, 493.20, 493.21, 493.22,
and 496), or those with a primary diagnosis of respiratory failure
(codes: 518.81, 518.82, 518.84, and 799.1) and a secondary
diagnosis of COPD.
We included only the ﬁrst hospitalization
for AECOPD for each patient during the study period. Then, we
further identiﬁed aspirin users by using the ICD-9-CM code for
long-term (current) use of aspirin (V58.66) in any diagnostic ﬁeld at
The outcome measures were in-hospital death (SID does not
include the information on the cause of death), the use of
mechanical ventilation (invasive mechanical ventilation [ICD-9-CM
procedure code 96.04] and non-invasive positive pressure
ventilation [NIPPV, code 96.30] assessed separately), and hospital
length-of-stay (LOS). To examine the association between aspirin
use and each outcome, we ﬁt unadjusted and adjusted logistic
regression or negative binomial regression models with general-
ized estimating equations to account for patient clustering within
hospitals. We adjusted for age, sex, race/ethnicity, payer, median
household income, 27 Elixhauser comorbidity measures (including
heart failure, arrhythmias, and valvular diseases), hospitalization
year, and hospital state. We repeated the analyses with (1)
excluding patients who had any of the cardiovascular comorbid-
ities that are commonly treated with aspirin (coronary artery
diseases [codes, 410–414] and ischemic stroke [codes, 433–434])
and (2) excluding these potential aspirin users and patients with
heart failure. All analyses were performed using STATA 14.1
(StataCorp, College Station, TX).
Overall, we identiﬁed 206,686 patients with hospitalization for
AECOPD in the seven US states. Of these, 13,826 patients (7%)
were aspirin users. Aspirin users were older, and more likely to
have Medicare comorbidities, compared to non-users (all P <
0.001; Table 1). Aspirin users had a signiﬁcantly lower in-hospital
mortality compared to non-users (1.0 vs. 1.4%; adjusted OR 0.60
[95% CI 0.50–0.72] P < 0.001; Table 2). Additionally, aspirin users
had a signiﬁcantly lower rate of invasive mechanical ventilation
use (1.7 vs. 2.6%; adjusted OR 0.64 [95% CI 0.55–0.73] P < 0.001),
while there was no signiﬁcant difference in the rate of NIPPV use
(7.6 vs. 7.2%; adjusted OR 1.05 [95% CI 0.98–1.12] P = 0.20).
Hospital LOS was signiﬁcantly shorter in aspirin users compared to
non-users (median, 3 days vs. 4 days), corresponding to −7%
change in the adjusted model (95% CI −5to−9%, P < 0.001). In
the sensitivity analysis excluding the patients with history of
coronary artery diseases, ischemic stroke, and/or heart failure, the
point estimates of these associations did not change materially.
Consistent with our ﬁndings, previous cohort studies have
reported that, among patients with COPD, the use of antiplatelet
therapy is associated with a lower long-term mortality.
Received: 8 October 2017 Revised: 25 January 2018 Accepted: 26 January 2018
Department of Emergency Medicine, Massachusetts General Hospital, 125 Nashua Street, Suite 920, Boston, MA 02114, USA
Correspondence: Tadahiro Goto (email@example.com)
Published in partnership with Primary Care Respiratory Society UK