Risk of Myocardial Infarction and Death Associated With the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Among Healthy Individuals: A Nationwide Cohort Study (original) (raw)
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PLOS ONE, 2018
Background Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used. Objectives To estimate the risk of AMI for individual NSAIDs. Methods A nested case-control study was performed from a cohort of new NSAID users �18 years (1999-2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time. Data were retrieved from six healthcare databases. Adjusted odds ratios (ORs) of current use of individual NSAIDs compared to past use were estimated per database. Pooling was done by two-stage pooling using a random effects model (ORmeta) and by one-stage pooling (ORpool). Results Among 8.5 million new NSAID users, 79,553 AMI cases were identified. The risk was elevated for current use of ketorolac (ORmeta 2.06;95%CI 1.83-2.32, ORpool 1.80; 1.49-2.18) followed, in descending order of point estimate, by indometacin, etoricoxib, rofecoxib, diclofenac, fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen,
Current Use of Nonsteroidal Antiinflammatory Drugs and the Risk of Acute Myocardial Infarction
Pharmacotherapy, 2005
To evaluate the risk of acute myocardial infarction during current exposure to nonsteroidal antiinflammatory drugs (NSAIDs). Retrospective case-control analysis. General practice offices. A total of 8688 case patients, aged 89 years or younger, with a first-time acute myocardial infarction and 33,923 control subjects matched on age, sex, calendar time, and general practice attended. The United Kingdom General Practice Research Database was searched for potential cases of first-time acute myocardial infarction between January 1995 and April 2001. Control subjects without acute myocardial infarction were identified at random. Exposure to NSAIDs was assessed, and 650 case patients and 2339 control subjects were found to be currently taking NSAIDs. After adjusting for various risk factors for acute myocardial infarction (e.g., hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease, body mass index, smoking), the relative risk (expressed as odds ratio [OR]) of acute myocardial infarction was 1.07 (95% confidence interval [CI] 0.96-1.19) for subjects with current NSAID exposure compared with those not taking NSAIDs. The adjusted OR for current diclofenac use was 1.23 (95% CI 1.00-1.51), for current ibuprofen use 1.16 (95% CI 0.92-1.46), and for current naproxen use 0.96 (95% CI 0.66-1.38) compared with those not taking NSAIDs. Current aspirin use combined with current NSAID use was associated with a statistically significant risk reduction (adjusted OR 0.74, 95% CI 0.57-0.97), compared with nonuse of NSAIDs and aspirin. Current use of aspirin together with current use of ibuprofen yielded an adjusted OR of 0.69 (95% CI 0.42-1.15). Our results provide additional evidence that the risk of first-time acute myocardial infarction during current use of NSAIDs is not materially altered. We found no evidence for a reduced cardioprotective effect of aspirin with concomitant NSAID use.
Archives of Internal Medicine, 2005
Background: It remains uncertain if the excess cardiovascular risk of rofecoxib and celecoxib reported in clinical trials is present in routine practice and whether the use of other nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) also carries an increased cardiovascular risk. We performed a population-based case-control study to examine the risk of myocardial infarction (MI) among users of various categories of nonaspirin NSAIDs.
Circulation: Cardiovascular Quality and Outcomes, 2010
Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4,614,807 individuals on January 1, 1997, of which 2,663,706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1,028,437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.
Arthritis Research & Therapy, 2006
The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22–1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88–1.11). In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen, supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so further investigation into the risk of AMI is warranted because the potential for harm can be substantial.
Pharmacoepidemiology and Drug Safety, 2007
Purpose To evaluate the association between rofecoxib, celecoxib, diclofenac, and ibuprofen and the risk of hospitalization for acute myocardial infarction (AMI) in an elderly population. Methods We conducted a retrospective cohort study, using data from the government of Quebec health insurance agency databases, among patients 65-80 years of age who filled a prescription for any of the study drugs during 1999-2002. Cox regression models with time-dependent exposure were used to compare the incidence rates of hospitalization for AMI adjusting for patients' baseline characteristics. Analyses stratified by dose and number of supplied days were also conducted. Results At the index date, a total of 91 062 patients were taking rofecoxib, 127 928 celecoxib, 49 193 diclofenac, and 15 601 ibuprofen. The adjusted hazard ratio (HR) (95%CI) of hospitalization for AMI were: celecoxib versus rofecoxib: 0.90 (0.79, 1.01); ibuprofen versus rofecoxib: 0.95 (0.65, 1.37); diclofenac versus rofecoxib: 1.01 (0.84, 1.22). In secondary analyses based on intended duration of use, neither COX-2 selective inhibitor was associated with a higher risk than ibuprofen or diclofenac. The unadjusted risk of AMI for all NSAIDs increased with dose. In the direct two way adjusted comparison of each NSAID stratified by dose, the only statistically significant difference was with rofecoxib >25 mg/day versus celecoxib >200 mg/day. Conclusion In this study there was no difference between AMI occurrence in elderly patients taking rofecoxib or celecoxib at recommended doses for chronic indications versus those taking ibuprofen/diclofenac. However, the risk of AMI was higher among patients using higher doses of rofecoxib (>25 mg/day) compared to patients using higher doses of celecoxib (>200 mg/day).
Cardiovascular risk of non-steroidal anti-inflammatory drugs
Vnitřní lékařství
Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the most widely used drugs. Results of recent large meta-analyses have shown that the cardiovascular risk of NSAIDs is more serious than originally believed and is not associated exclusively with coxibs; it is also increased when using so called traditional NSAIDs. Data obtained to date show the safest drugs of this class in terms of cardiovascular risk are naproxen and ibuprofen at low doses. The position of naproxen as the safest NSAID has been challenged by some more recent findings. The authors examine some results of meta-analyses and conclusions of regulatory agencies.