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Biomedical subjects

James M Brophy

Publications and source records attributed to James M Brophy.

At least 19 recordsLinked to original sources
PubMed2007

The impact of over-the-counter simvastatin on the number of statin prescriptions in the United Kingdom: a view from the General Practice Research Database.

PURPOSE: The United Kingdom (UK) government changed the prescription policy of statins, making low-dose simvastatin (10 mg) available as an over-the-counter (OTC) drug in August 2004. We assessed the impact of this policy change on statin prescribing. METHODS: We examined all statin prescriptions in the General Practice Research Database (GPRD), a well-validated database of approximately 3.5 million patients, from the first quarter of 2001 to the second quarter of 2005. RESULTS: From 2001, the number of statin prescriptions written for GPRD patients was increasing by approximately 437 prescriptions per 100,000 people per quarter until the time of the policy change. Over the four quarters post-policy implementation, however, this trend changed abruptly (p < 0.0001) with a decrease of 281 prescriptions per 100,000 people per quarter. This decrease was not restricted to prescriptions of 10 mg statins but was also observed for statin prescriptions of >or=20 mg. Several other cardiovascular medications displayed a similar trend as that observed in the number of statin prescriptions. This trend was not observed among non-cardiovascular control medications. CONCLUSIONS: Our study suggests that the policy allowing the OTC sale of 10 mg simvastatin has had a significant impact on statin prescriptions by general practitioners. However, this new policy may also be leading to less aggressive statin therapy. An alternative explanation for the observed decrease in statin prescriptions may be related to the unknown factors responsible for the overall decrease observed with other cardiovascular prescription drugs.

Databases, Factual↗
PubMed2006

The cost-effectiveness of drug-eluting stents: a systematic review.

BACKGROUND: Drug-eluting stents have been seen as an attractive alternative to bare-metal stents for percutaneous coronary interventions (PCIs) because of the decreased need for revascularization. However, comparative clinical trials have shown no difference in patient outcomes, and drug-eluting stents are considerably more expensive than their bare-metal counterparts. We conducted a systematic review of all published comparative cost-effectiveness analyses to identify the factors contributing to the heterogeneity of their conclusions. METHODS: We retrieved all articles published between Jan. 1, 2000, and July 31, 2006, in which the cost-effectiveness, from a third-party payer perspective, of drug-eluting stents was compared with that of bare-metal stents for PCI in unrestricted patient populations. Electronic databases, Web sites from health technology assessment groups and references of identified articles were searched. Our outcome variable was whether the study's conclusions favoured widespread use of drug-eluting stents, as assessed by 4 independent reviewers. Study characteristics such as quality, funding source, country and year of publication were extracted. Two-by-2 tables and Fisher's exact test were used to study the association between covariates and the outcome variable. A classification and regression tree (CART) model was used for multivariate analysis. RESULTS: We identified 19 cost-effectiveness analyses. Ten were in favour of widespread use of drug-eluting stents, and 9 favoured more restrained use. Only 1 of 9 high-quality studies supported widespread use, as compared with 9 of 10 lower quality studies (p < 0.001). All of the 7 sponsored studies argued in favour of widespread use, as compared with 3 of the 12 studies without sponsorship (p = 0.003). Studies from the United States were more likely than those from other countries to endorse unlimited use (p = 0.032). A CART model with 2 covariates--study quality and sponsorship--provided the best fit (error rate 10.5%). INTERPRETATION: Conclusions drawn by cost-effectiveness analyses of drug-eluting stents for PCI are associated with the study's quality, funding source and country of origin. Vigilance regarding these study characteristics is required when interpreting findings from cost-effectiveness analyses.

Coronary Artery Disease↗
PubMed2006

Acute ischemic heart disease and interventional cardiology: a time for pause.

BACKGROUND: A major change has occurred in the last few years in the therapeutic approach to patients presenting with all forms of acute coronary syndromes. Whether or not these patients present initially to tertiary cardiac care centers, they are now routinely referred for early coronary angiography and increasingly undergo percutaneous revascularization. This practice is driven primarily by the angiographic image and technical feasibility. Concomitantly, there has been a decline in expectant or ischemia-guided medical management based on specific clinical presentation, response to initial treatment, and results of noninvasive stratification. This 'tertiarization' of acute coronary care has been fueled by the increasing sophistication of the cardiac armamentarium, the peer-reviewed publication of clinical studies purporting to show the superiority of invasive cardiac interventions, and predominantly supporting (non-peer-reviewed) editorials, newsletters, and opinion pieces. DISCUSSION: This review presents another perspective, based on a critical reexamination of the evidence. The topics addressed are: reperfusion treatment of ST-elevation myocardial infarction; the indications for invasive intervention following thrombolysis; the role of invasive management in non-ST-elevation myocardial infarction and unstable angina; and cost-effectiveness and real world considerations. A few cases encountered in recent practice in community and tertiary hospitals are presented for illustrative purposes The numerous and far-reaching scientific, economic, and philosophical implications that are a consequence of this marked change in clinical practice as well as healthcare, decisional and conflict of interest issues are explored. SUMMARY: The weight of evidence does not support the contemporary unfocused broad use of invasive interventional procedures across the spectrum of acute coronary clinical presentations. Excessive and unselective recourse to these procedures has deleterious implications for the organization of cardiac health care and undesirable economic, scientific and intellectual consequences. It is suggested that there is need for a new equilibrium based on more refined clinical risk stratification in the treatment of patients who present with acute coronary syndromes.

Acute Disease↗
PubMed2006

Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis.

Conventional nonsteroidal antiinflammatory drugs (NSAIDs) are associated with acute renal failure, but cyclooxygenase-2 inhibitors have not been comparatively evaluated. The authors conducted a nested case-control study to assess the association between exposure to NSAIDs, including cyclooxygenase-2 inhibitors, and hospitalization for acute renal failure. They identified 121,722 new NSAID users older than age 65 years from the administrative health care databases of Quebec, Canada, in 1999-2002. Data for 4,228 cases and 84,540 controls matched on age and follow-up time were analyzed by using conditional logistic regression, adjusted for sex, age, health status, health care utilization measures, exposure to contrast agents, and nephrotoxic medications. The risk of acute renal failure for all NSAIDs combined was highest within 30 days of treatment initiation (adjusted rate ratio (RR) = 2.05, 95% confidence interval (CI): 1.61, 2.60) and receded thereafter. The association with acute renal failure within 30 days of therapy initiation was comparable for rofecoxib (RR = 2.31, 95% CI: 1.73, 3.08), naproxen (RR = 2.42, 95% CI: 1.52, 3.85), and nonselective, non-naproxen NSAIDs (RR = 2.30, 95% CI: 1.60, 3.32) but was borderline lower for celecoxib (RR =1.54, 95% CI: 1.14, 2.09; test for interaction comparing celecoxib with rofecoxib, p = 0.057). There was a significant association for both selective and nonselective NSAIDs with acute renal failure, but confirmatory studies are required.

Acute Kidney Injury↗
PubMed2006

The risk of death associated with delayed coronary artery bypass surgery.

BACKGROUND: The detrimental effect of delaying surgical revascularization has been estimated in randomized trials and observational studies. It has been argued that the Kaplan-Meier method used in quantifying the hazard of delayed treatment is not appropriate for summarizing the probability of competing outcomes. Therefore, we sought to improve the estimates of the risk of death associated with delayed surgical treatment of coronary artery disease. METHODS: Population-based prospective study of 8,325 patients registered to undergo first time isolated coronary artery bypass grafting (CABG) in any of the four tertiary hospitals that provide cardiac care to adult residents of British Columbia, Canada. The cumulative incidence of pre-operative death, the cumulative incidence of surgery, and the probability that a patient, who may die or undergo surgery, dies if not operated by certain times over the 52-week period after the decision for CABG were estimated. The risks were quantified separately in two groups: high-severity at presentation were patients with either persistent unstable angina or stable angina and extensive coronary artery disease, and low-severity at presentation were stable symptomatic patients with limited disease. RESULTS: The median waiting time for surgery was 10 weeks (interquartile range [IQR] 15 weeks) in the high-severity group and 21 weeks (IQR 30 weeks) in the low-severity group. One percent of patients died before surgery: 54 in the high-severity and 26 in the low-severity group. For 58 (72.5%) patients, death was related to CVD (acute coronary syndrome, 33; chronic CVD, 16; other CVD, 4; and sudden deaths, 5). The overall death rate from all causes was 0.61 (95% CI 0.48-0.74) per 1,000 patient-weeks, varying from 0.62 (95% CI 0.45-0.78) in the high-severity group to 0.59 (95% CI 0.37-0.82) in the low-severity group. After adjustment for age, sex, and comorbidity, the all-cause death rate in the low-severity group was similar to the high-severity group (OR = 1.02, 95% CI 0.64-1.62). The conditional probability of death was greater in the high-severity group than in the low-severity group both for all-cause mortality (p = 0.002) and cardiovascular deaths (p <0.001). CONCLUSION: The probability of death conditional on not having undergone a required CABG increases with time spent on wait lists.

Adult↗
PubMed2006

Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease.

OBJECTIVES: The purpose of this study was to determine if statins (hydroxymethylglutaryl CoA reductase inhibitors [HMG-CoA]), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) reduce cardiovascular (CV) events and pulmonary morbidity in chronic obstructive pulmonary disease (COPD) patients. BACKGROUND: Few current COPD therapies alter prognosis. Although statins, ACE inhibitors, and ARBs improve outcomes in CV populations, their benefits in COPD patients both with and without concomitant heart disease has not previously been studied. METHODS: A time-matched nested case-control study of two population-based retrospective cohorts was undertaken: 1) COPD patients having undergone coronary revascularization (high CV risk cohort); and 2) COPD patients without previous myocardial infarction (MI) and newly treated with nonsteroidal anti-inflammatory drugs (low CV risk cohort). Prespecified outcomes were COPD hospitalization, MI, and total mortality. RESULTS: These drugs reduced both CV and pulmonary outcomes, with the largest benefits occurring with the combination of statins and either ACE inhibitors or ARBs. This combination was associated with a reduction in COPD hospitalization (risk ratio [RR] 0.66, 95% confidence interval [CI] 0.51 to 0.85) and total mortality (RR 0.42, 95% CI 0.33 to 0.52) not only in the high CV risk cohort but also in the low CV risk cohort (RR 0.77, 95% CI 0.67 to 0.87, and RR 0.36, 95% CI 0.28 to 0.45, respectively). The combination also reduced MI in the high CV risk cohort (RR 0.39, 95% CI 0.31 to 0.49). Benefits were similar when steroid users were included. CONCLUSIONS: These agents may have dual cardiopulmonary protective properties, thereby substantially altering prognosis of patients with COPD. These findings need confirmation in randomized clinical trials.

Aged↗
PubMed2006

Time variations in the risk of myocardial infarction among elderly users of COX-2 inhibitors.

BACKGROUND: The timing of cardiovascular risks associated with the use of cyclooxygenase-2 (COX-2) inhibitors is unclear. Using data collected in a previous population-based cohort study of elderly people starting nonsteroidal anti-inflammatory drug (NSAID) therapy, we evaluated the temporal nature of the risk of a first myocardial infarction (MI) associated with the use of rofecoxib and celecoxib. METHODS: We identified people 66 years of age or older without previous MI who were currently taking rofecoxib and celecoxib using Quebec's computerized health databases (January 1999 to June 2002). Data on use and MI outcome were analyzed using a time-matched, nested case-control approach with rate ratios, comparing current users and non-users of rofecoxib and celecoxib in the year preceding the index date, estimated using conditional logistic regression. RESULTS: The risk of MI was highest following first-time use of rofecoxib (adjusted rate ratio [RR] 1.67, 95% confidence interval [CI] 1.21-2.30), with events occurring within a median of 9 (6-13) days after therapy was started. The risk increase for first-time use of celecoxib was not statistically significant (RR 1.29, 95% CI 0.90-1.83). Repeated exposure to rofecoxib was associated with a small but statistically nonsignificant delayed risk (RR 1.17, 95% CI 0.98-1.40), but no risk was seen with celecoxib (RR 0.97, 95% CI 0.82-1.14). Treatment duration was not associated with increasing risk for either agent. The risk remained elevated for the first 7 days after rofecoxib was discontinued (RR 1.23, 95% CI 1.05-1.44) but appeared to return to baseline between day 8 and 30 (RR 0.82, 95% CI 0.61-1.09). INTERPRETATION: A small proportion of patients using rofecoxib for the first time had their first MI shortly after starting the drug. This risk did not increase with the length of treatment and returned to baseline shortly after treatment was discontinued. More research is needed to identify those most susceptible to cardiotoxicity mediated by COX-2 inhibitor therapy.

Age Factors↗
PubMed2006

A pharmacoepidemiology study of the interaction between atorvastatin and clopidogrel after percutaneous coronary intervention.

BACKGROUND: After percutaneous coronary intervention (PCI), the antiplatelet drug clopidogrel is frequently used to prevent stent thrombosis. A concern has been raised that atorvastatin may competitively inhibit the metabolism of the prodrug clopidogrel to its active metabolites by the cytochrome P450 3A4 (CYP3A4) enzyme, thereby potentially negating its antiplatelet effect. The 30-day rates of adverse cardiovascular events (composite of death, myocardial infarction, 11 unstable angina, stroke or transient ischemic attack, and repeat revascularization procedures) in unselected 12 patients prescribed clopidogrel after PCI as a function of their exposure to CYP3A4 inhibitors has not been fully resolved. METHODS: Using the administrative databases from the Province of Québec, we identified all patients in 1999 and 2000 who received an outpatient prescription for clopidogrel within 5 days of PCI with stenting. Using multiple logistic regression, we compared the odds ratios (OR) of the composite cardiovascular outcome within 30 days of the index PCI between patients prescribed drugs inhibiting CYP3A4 activity and those who were not. Event rates were adjusted for demographic variables, disease severity, associated comorbidities, and other medications. RESULTS: The 2927 patients who were prescribed clopidogrel after PCI were included in our cohort. Of these, 727 were prescribed atorvastatin and 2200 were not. There were 33 (4.54%) adverse events in the group prescribed atorvastatin and 68 (3.09%) in the group not prescribed atorvastatin. The adjusted 30-day OR of the composite outcome was 1.65 (95% CI 1.07-2.54) in patients prescribed atorvastatin with clopidogrel compared to those not prescribed atorvastatin. Other drugs that are substrates for CYP3A4 (OR 1.56, 95% CI 1.02-2.37) and a delay in filling the clopidogrel prescription (OR 1.77, 95% CI 1.16-2.70) were also associated with a higher risk. Sex, previous hospitalizations for unstable angina or myocardial infarction, aspirin use, or a history of revascularization (PCI or coronary artery bypass graft) in the 6 months before the index procedure was not statistically associated with adverse outcomes. CONCLUSIONS: After coronary stenting, a delay in filling the prescription for clopidogrel as well as prescriptions for drugs inhibiting CYP3A4 enzyme activity was associated with adverse cardiovascular events. However, because of the limitations of observational study designs, the clinical significance of these putative drug interactions remains uncertain but merits further investigation.

Aged↗
PubMed2006

Statin wars following coronary revascularization--evidence-based clinical practice?

BACKGROUND: Randomized clinical trials (RCTs) have shown that statins provide substantial heath benefits. Pharmaceutical companies spend enormous amounts of money on both clinical trials and marketing. The relative influence of information from clinical trials on physician prescription patterns for statins is unknown. OBJECTIVE: To examine the correlation between statin prescription patterns and the quality of evidence from RCTs. METHODS: Using the computerized administrative databases of the Quebec Health Insurance Board, the choice of statin for elderly patients (older than 65 years of age) following a coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft surgery) performed between January 1, 1994, and June 30, 2003, was examined. Prescriptions for each statin were compared with their evidence base obtained from a cumulative systematic literature review of RCTs that recorded mortality as an outcome and were published before December 31, 2002. RESULTS: The study cohort comprised 27,979 elderly revascularized patients who received at least one statin prescription. In 1996, the year atorvastatin was introduced, simvastatin and pravastatin had 38.3% and 37.1% of the market share, respectively. By 2003, atorvastatin had 44% of the market share, compared with 29.9% and 24.1% for simvastatin and pravastatin, respectively. In contrast, RCTs published up to the end of 2002 had culminated in 133,341 and 140,565 patient-years of follow-up for simvastatin and pravastatin, respectively, and only 1459 patient-years for atorvastatin. CONCLUSIONS: Prescription patterns regarding the choice of statin do not appear to be determined uniquely from high-quality RCTs. Further research into the other possible determinants of physician prescription patterns is necessary.

Aged↗
PubMed2006

Treating the right patient at the right time: access to specialist consultation and non-invasive testing.

The Council of the Canadian Cardiovascular Society commissioned working groups to examine issues of access to, and wait times for, various aspects of cardiovascular care. The present article summarizes the deliberations on targets for medically acceptable wait times for access to cardiovascular specialist evaluation and on the performance of noninvasive testing needed to complete this evaluation. Three categories of referral indications were identified: those requiring hospitalization due to substantial ongoing risk of mortality and morbidity; those requiring an expedited early review in an ambulatory setting; and, finally, a larger category in which delays of two to six weeks can be justified. The proposed wait time targets will provide guidance on the timeliness of care to busy clinicians charged with the care of patients with cardiovascular disease, help policy makers appreciate the clinical challenges in providing access to high quality care, and highlight the critical need for a thoughtful review of cardiology human resource requirements. Wait time implementation suggestions are also included, such as the innovative use of disease management and special need clinics. The times proposed assume that available clinical practice guidelines are followed for clinical coronary syndrome management and for treatment of associated conditions such as hypertension, diabetes, renal disease, smoking cessation and lipid disorders. Although media attention tends to focus on wait times for higher profile surgical procedures and high technology imaging, it is likely that patients face the greatest wait-related risk at the earlier phases of care, before the disease has been adequately characterized.

Canada↗
PubMed2006

Do angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers decrease the risk of hospitalization secondary to community-acquired pneumonia? A nested case-control study.

STUDY OBJECTIVE: As studies have shown that angiotensin-converting enzyme (ACE) inhibitors may lower the risk of developing pneumonia by increasing the cough reflex, we sought to explore the potential association between use of ACE inhibitors and the risk of hospitalization secondary to community-acquired pneumonia (CAP). To test this hypothesis further, we also looked at the risk for CAP in those taking angiotensin II receptor blockers (ARBs), as these drugs have a similar mechanism of action to that of ACE inhibitors but have minimal or no effect on the cough reflex. In addition, the putative protection against pneumonia may instead be related to general inhibition of the renin-angiotensin system. DESIGN: Nested case-control study. DATA SOURCE: Universal Quebec, Canada, administrative health databases. PATIENTS: From a cohort of 47,148 patients with coronary artery disease who had a revascularization procedure between 1996 and 2000, 1666 patients with CAP and 33,315 time-matched control subjects (20 controls for each case) were identified. MEASUREMENTS AND MAIN RESULTS: Conditional logistic regression analysis was used to estimate rate ratios, while controlling for potential confounders. No association was observed between patients receiving ACE inhibitors and hospitalization for CAP (rate ratio [RR] 0.98, 95% confidence interval [CI] 0.69-1.40). A similar lack of association was noted for those receiving ARBs (RR 1.02, 95% CI 0.70-1.49). CONCLUSION: In this case-control study, no association was found between use of ACE inhibitors or ARBs and risk of hospitalization secondary to CAP. Future studies are necessary to explore this association further.

Aged↗
PubMed2005

Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review.

BACKGROUND: The recent increase in the number and severity of cases of nosocomial Clostridium difficile-associated diarrhea (CDAD) has prompted interest in the use of probiotics for the prevention and treatment of this disease. We performed a systematic review of randomized controlled trials to assess the effectiveness of probiotic therapy. METHODS: We searched the PubMed, EMBASE, INAHTA, HEN and Cochrane Collaboration databases to identify trials in which the prevention or treatment of CDAD with probiotic therapy was the primary or secondary outcome. We extracted data on the number of patients randomly assigned to receive probiotic or placebo, the number of patients with CDAD, the type of probiotic, criteria for diagnosing CDAD, persistence of infection after treatment, compliance and adverse effects. RESULTS: We identified 4 eligible studies in which prevention (n = 1) or treatment (n = 3) of CDAD was the primary outcome. The benefit of probiotic therapy seen in 2 of the studies was restricted to subgroups characterized by severe CDAD and increased use of vancomycin. The remaining 2 studies were too methodologically flawed for us to draw meaningful conclusions. We also identified 4 trials in which prevention of antibiotic-associated diarrhea with probiotics was the primary outcome and prevention of CDAD a secondary outcome. These studies were limited primarily by too few CDAD cases and provided no evidence of effective prophylaxis. Overall, heterogeneity in choice and dose of probiotic and in criteria for diagnosing CDAD makes it difficult to synthesize information from the 8 studies. INTERPRETATION: Studies conducted to date provide insufficient evidence for the routine clinical use of probiotics to prevent or treat CDAD. Better designed and larger studies are needed.

Clostridioides difficile↗
PubMed2005

Impact of care at a multidisciplinary congestive heart failure clinic: a randomized trial.

BACKGROUND: Although multidisciplinary congestive heart failure clinics in the United States appear to be effective in reducing the number of hospital readmissions, it is unclear whether the same benefit is seen in countries such as Canada, where access to both general and specialized medical care is free and unrestricted. We sought to determine the impact of care at a multidisciplinary specialized outpatient congestive heart failure clinic compared with standard care. METHODS: We randomly assigned 230 eligible patients who had experienced an acute episode of congestive heart failure to standard care (n = 115) or follow-up at a multidisciplinary specialized heart failure outpatient clinic (n = 115). The intervention consisted of a structured outpatient clinic environment with complete access to cardiologists and allied health professionals. The primary outcomes were all-cause hospital admission rates and total number of days in hospital at 6 months. The secondary outcomes were total number of emergency department visits, quality of life and total mortality. RESULTS: At 6 months, fewer patients in the intervention group had required readmission to hospital than patients in the control group (45 [39%] v. 66 [57%], crude hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.38-0.92. Patients in the intervention group stayed in hospital for 514 days compared with 815 days required by patients in the control group (adjusted HR 0.56, 95% CI 0.35-0.89). The number of patients seen in the emergency department and the total number of emergency department visits were similar in the intervention and control groups. At 6 months, quality of life, which was self-assessed using the Minnesota Living with Heart Failure questionnaire, was unchanged in the control group but improved in the intervention group (p < 0.001). No difference in mortality was observed, with 19 deaths in the control group and 12 in the intervention group (HR 0.61, 95% CI 0.24-1.54). INTERPRETATION: Compared with usual care, care at a multidisciplinary specialized congestive heart failure outpatient clinic reduced the number of hospital readmissions and hospital days and improved quality of life. When our results are integrated with those from other, similar trials, multidisciplinary disease management strategies for congestive heart failure are associated with clinically worthwhile improvements in survival.

Aged↗
PubMed2005

The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults.

BACKGROUND: Cyclooxygenase-2 (COX-2) selective inhibitors have been marketed since 1999 as safer alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs). Debate about their cardiac safety has culminated in the recent withdrawal of rofecoxib. Additional studies are needed to better understand this risk and to determine whether this safety concern represents a class effect. OBJECTIVE: To assess the influence of various NSAIDs on the risk for a first myocardial infarction (MI). DESIGN: Population-based, retrospective cohort study analyzed using a time-matched, nested case-control approach. SETTING: Quebec, Canada. PARTICIPANTS: 113,927 elderly persons without previous MI and newly treated with an NSAID between 1 January 1999 and 30 June 2002. MEASUREMENTS: NSAID exposure and occurrence of MI assessed by using Quebec's administrative health databases. RESULTS: Compared with no use of NSAIDs in the year preceding the event, current use of rofecoxib was associated with an increased risk for an acute MI (rate ratio [RR], 1.24 [95% CI, 1.05 to 1.46]) that was more pronounced at higher doses (RR, 1.73 [CI, 1.09 to 2.76]). The concomitant use of aspirin appears to decrease the risk associated with low-dose rofecoxib (RR, 1.00 [CI, 0.77 to 1.28]) but not with high-dose rofecoxib (RR, 2.36 [CI, 1.27 to 4.39]). No increased risks were observed with celecoxib (RR, 0.99 [CI, 0.85 to 1.16]) or the other NSAIDs. LIMITATIONS: The study could not completely account for all potential confounders, including over-the-counter use of aspirin and ibuprofen. CONCLUSIONS: These results provide evidence of an increased risk for acute MI in current users of rofecoxib among elderly persons with no history of MI. This risk appears greater at higher doses. Aspirin use mitigates the risk associated with low-dose but not high-dose rofecoxib. There was no evidence of an increased risk with the other NSAIDs.

Aged↗