NSAIDs acute myocardial infarction Use of in patients with

Use of
NSAIDs in patients with acute myocardial infarction
Alain Vanasse, MD PhD1,2
Artur de Brum-Fernandes, MD PhD2,3
Josiane Courteau, PhD2
Danielle Pilon, MD MSc3
2. Centre de Recherche Clinique Étienne-Le Bel, Université de Sherbrooke, Sherbrooke, Québec
3. Département de médecine, Université de Sherbrooke, Sherbrooke, Québec
Groupe de recherche PRIMUS: www.pages.usherbrooke.ca/primus
Groupe de recherche
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In Lee et al, the risk of all-cause death was
reduced among non-selective NSAIDs users,
even in the high risk population with a
preexisting coronary artery disease and is not
related to the NSAIDs used (Naproxen,
Ibuprofen, Diclofenac, other NSAIDs)
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Similarly, Stürmer et al showed a significant
decreased death risk associated to non-selective
NSAIDs
On the other hand, Gislason et al found a
significant increased risk of death associated
with both Ibuprofen and Diclofenac in a
population with AMI, but this risk seemed to
be observed with high daily dosage only. With
low dosage of Ibuprofen, the risk of death was
significantly decreased
Finally, MacDonald et al showed a significant
increased risk of both all-cause and
cardiovascular death with aspirin and Ibuprofen
as compared to aspirin alone, but a non
significant decrease with aspirin and Diclofenac
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Cardiovascular mortality
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Recurrent AMI
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5837 (21.8%) patients died
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3634 (13.5%) died from a cardiovascular disease
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2611 (9.7%) were readmitted for AMI
This was particularly true for diclofenac users as compared to
non diclofenac users
NSAIDs users were less likely to die from cardiovascular
disease than non NSAIDs users
This was particularly true for naproxen users as compared to
non naproxen users
Characteristics of population according to event-points
CVD DEATH
ALL-CAUSE DEATH
Cases
(n=5837)
Controls
(n=116668)
p-value
Cases
(n=3634)
AMI REHOSPITALIZATION
Controls
(n=72623)
p-value
Cases
(n=2611)
Controls
(n=52203)
p-value
Gender , %
Female
0.978
47.4
0.972
44.7
53.8
53.8
52.6
52.5
55.3
55.3
77.8 (7.2)
77.1 (6.7)
< .001
77.9 (7.2)
77.3 (6.7)
< .001
76.0 (6.7)
75.6 (6.5)
0.002
2.5 (2.2)
1.5 (1.7)
< .001
2.4 (2.0)
1.5 (1.7)
< .001
1.9 (1.8)
1.5 (1.7)
< .001
17.3 (22.5)
15.9 (20.8)
< .001
16.8 (20.0)
15.9 (20.7)
< .001
13.4 (12.3)
15.9 (20.0)
< .001
3.4
9.3
< .001
3.0
9.0
< .001
4.6
10.9
< .001
Aspirin
30.9
52.3
< .001
35.5
52.2
< .001
51.5
54.1
Beta-blockers
15.9
33.8
< .001
18.7
33.8
< .001
33.4
36.3
0.002
ACE
28.9
32.1
< .001
33.7
32.0
< .001
36.9
31.8
< .001
3.4
8.4
< .001
3.9
8.0
< .001
7.8
8.7
0.094
175 (3.0)
Male
Age, mean (SD) (y)
Methods
Methods
Comorbidity, mean (SD)
Length of stay, mean (SD) (d)
Revascularization, %
46.2
6.2
47.5
44.7
No statistically significant increased risk of recurrent
AMI was observed in NSAIDs users
0.994
Cardioprotective drugs, %
Design
We conducted matched nested case-control studies
in a retrospective population-based cohort
Covariables
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Study population
The cohort includes all elderly patients living in
Quebec and hospitalized for an AMI between 1992
and 1996. Patients with an AMI in the year
preceding index hospitalization or who died at index
hospitalisation were excluded
Data sources
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in a population with AMI in the province of Quebec
Like selective NSAIDs (COX-2), nonselective NSAIDs have raised
concerns based on several studies
reporting an increased risk of
cardiovascular events
Mortality studies show contradictory
results
Mortality
NSAIDs users were less likely to die than non NSAIDs
users
During the 2-year period following hospital discharge
The objective of the study was to measure the impact of
exposition to NSAIDs on:
Non-steroidal
anti-inflammatory
drugs (NSAIDs) are drugs used to
reduce pain, fever and inflammation
Summary
Summary
A total of 26,822 patients survived a « new » AMI
hospitalization between 1992 and 1996 in the province of
Quebec
Objective
Objective
Introduction
Introduction
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Results
Results
Fonds de la recherche
en santé
PRIMUS
Few studies show the impact of nonselective NSAIDs on all-cause and
cardiovascular mortality in the
general population and even fewer
in the high-risk population of
patients who survived an acute
myocardial infarction (AMI)
and its impacts on cardiovascular outcomes
1. Département de médecine de famille, Université de Sherbrooke, Sherbrooke, Québec
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Provincial hospital discharge database (Med-Echo)
Provincial death register
Provincial beneficiary database (RAMQ)
Provincial pharmacological database (RAMQ)
Study outcomes
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All-cause death
Cardiovascular death (ICD-10: I20-I25, I44-I52)
Hospital readmission for AMI (ICD-9: 410)
Drug expositions
Every patient who filled a prescription at a pharmacy
was considered exposed to the drug for the length of
time of the prescription
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Age
Gender
Comorbidity index
Length of stay at index hospitalization
Revascularization (PTCA or CABG) at index hospitalization
Exposure to cardio-protective drugs
Aspirin, Beta-blockers, ACE inhibitors, Statins
Statins
0.008
NSAID exposure, n (%)
Any NSAIDs
4779 (4.1)
< .001
93 (2.6)
4779 (4.1)
< .001
117 (4.5)
2141 (4.1)
0.341
Ibuprofen
11 (0.2)
317 (0.3)
0.230
7 (0.2)
194 (0.3)
0.393
8 (0.3)
153 (0.3)
0.902
Naproxen
42 (0.7)
1174 (1.0)
0.031
16 (0.4)
710 (1.0)
0.001
26 (1.0)
542 (1.0)
0.834
Diclofenac
42 (0.7)
1492 (1.3)
< .001
28 (0.8)
880 (1.2)
0.017
32 (1.2)
633 (1.2)
0.953
Other NSAIDs
80 (1.4)
1873 (1.6)
0.162
42 (1.2)
1114 (1.5)
0.069
53 (2.0)
848 (1.6)
0.112
This study shows no statistically significant increased
risk of recurrent AMI in NSAIDs users and their risk of
cardiovascular death is reduced
Hazard Ratio (HR)
Selection of cases and controls
For each outcome, 20 controls per case were randomly
drawn from each case’s risk set
Matched for age (±5 years), gender and date of
cohort entry (±30 days)
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Statistical analyses
Conditional logistic regressions were used to estimate the
hazard ratios (HR) of outcome events associated with
NSAIDs
Models were adjusted for comorbidity index, length
of stay and revascularization at index hospitalization,
and exposures to aspirin, beta-blockers, ACE
inhibitors and statins
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0.33
0.5
1
2
3
Adjusted HR
(95% CI)
ALL-CAUSE DEATH
Adjusted* hazard ratios (HR)
with their 95% confidence
intervals estimated from
the conditional logistic
regression analyses
*Adjusted for age, gender, time of cohort entry, hospital
length of stay and revascularization at index
hospitalization, exposure to aspirin, ACE inhibitors, beta
blockers and statins
Any NSAIDs
0.84 (0.72-0.98) *
Ibuprofen
0.79 (0.43-1.44)
Naproxen
0.81 (0.59-1.11)
Diclofenac
0.69 (0.50-0.92) *
Other NSAIDs
0.97 (0.77-1.22)
Conclusions
Conclusions
Further studies are needed to better understand the
mechanisms implicated in these effects
CVD DEATH
Any NSAIDs
0.72 (0.58-0.89) *
Ibuprofen
0.81 (0.38-1.73)
Naproxen
0.51 (0.31-0.84) *
Diclofenac
0.74 (0.50-1.08)
Other NSAIDs
0.80 (0.59-1.10)
References
AMI READMISSION
Any NSAIDs
1.08 (0.89-1.31)
Ibuprofen
1.04 (0.51-2.14)
Naproxen
0.96 (0.65-1.43)
Diclofenac
1.01 (0.70-1.44)
Vanasse A, Pilon D, Courteau J, de Brum-Fernandes A. Use of cyclooxygenase2 inhibitors with patients with acute myocardial infarction and its impact on
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1.22 (0.92-1.62)
Other NSAIDs
0.33
0.5
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2
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