Association of non-steroidal anti-inflammatory drugs with outcomes in patients with ST-segment elevation myocardial infarction treated with fibrinolytic therapy: an ExTRACT-TIMI 25 analysis.
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) may be prothrombotic, may worsen hypertension or congestive heart failure and obstruct access to the binding site of aspirin to cyclooxygenase-1 and thereby interfere with aspirin's mechanism of action in reducing death and recurrent myocardial infarction (MI). We hypothesized that treatment with NSAIDs prior to an index MI would be associated with an increase in the risk of death, heart failure and recurrent MI among patients with ST-segment elevation MI (STEMI) treated with fibrinolytic therapy.


METHODS
In ExTRACT-TIMI 25, patients with STEMI were treated with aspirin and fibrinolytic therapy and randomized to either enoxaparin or unfractionated heparin. We included patients who had received NSAIDs within 7 days of enrollment and evaluated the incidence of MI, the composite of death and MI and the composite of death, MI, severe heart failure and shock through 30 days.


RESULTS
Of 20,479 patients enrolled, 572 (2.8%) received an NSAID within 7 days of enrollment. NSAID treatment prior to entry was associated with a higher incidence of 30-day death or nonfatal recurrent MI (15.9% vs. 10.8%, univariate P < 0.001). In multivariable models adjusting for randomization group and differences in baseline characteristics, NSAID use was associated with higher odds of MI (adjusted odds ratio [OR(adj)] 1.44, 95% confidence interval [CI] 1.01-2.07, P = 0.047), the composite of death and MI (OR(adj) 1.29, 95% CI 1.00-1.66, P = 0.051), and the composite of death, MI, severe heart failure and shock (OR(adj) 1.29, 95% CI 1.02-1.65, P = 0.037).


CONCLUSIONS
Among STEMI patients treated with a fibrinolytic agent and aspirin, use of NSAIDs in the week preceding the incident event was associated with a higher incidence of MI, the composite of death and MI as well as the composite of death, MI, severe heart failure and shock at 30 days.
Gibson
C Michael
CM
TIMI Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 350 Longwood Avenue, First Floor, Boston, MA 02115, USA. mgibson@perfuse.org
Pride
Yuri B
YB
Aylward
Philip E
PE
Col
Jacques J
JJ
Goodman
Shaun G
SG
Gulba
Dietrich
D
Bergovec
Mijo
M
Kunadian
Vijayalakshmi
V
Zorkun
Cafer
C
Buros
Jacqueline L
JL
Murphy
Sabina A
SA
Antman
Elliott M
EM
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015897:Comorbidity; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D015912:Thrombolytic Therapy / Q000009:adverse effects; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D016861:Cyclooxygenase Inhibitors; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006493:Heparin; D001241:Aspirin