Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure.
BACKGROUND
Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF.


METHODS
We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models.


RESULTS
A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results.


CONCLUSIONS
NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.
Gislason
Gunnar H
GH
Department of Cardiology, Gentofte University Hospital, Niels Andersens Vej 65, 2900 Hellerup, Denmark. gg@heart.dk
Rasmussen
Jeppe N
JN
Abildstrom
Steen Z
SZ
Schramm
Tina K
TK
Hansen
Morten L
ML
Fosbøl
Emil L
EL
Sørensen
Rikke
R
Folke
Fredrik
F
Buch
Pernille
P
Gadsbøll
Niels
N
Rasmussen
Søren
S
Poulsen
Henrik E
HE
Køber
Lars
L
Madsen
Mette
M
Torp-Pedersen
Christian
C
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality*; D012307:Risk Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal