Cardiovascular risk and inhibition of cyclooxygenase: A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2

Patricia McGettigan, David Henry

Research output: Contribution to journalReview articleResearchpeer-review

866 Citations (Scopus)

Abstract

Context: Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older non-selective NSAIDs. Objective: To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors. Data Sources: Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies. Study Selection: Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs. Data Extraction: Two people independently extracted data and assessed study quality with disagreements resolved by consensus. Data Synthesis: Data were combined using a random-effects model. A doserelated risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18). Conclusions: This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.

Original languageEnglish
Pages (from-to)1633-1644
Number of pages12
JournalJournal of the American Medical Association
Volume296
Issue number13
DOIs
Publication statusPublished - 4 Oct 2006
Externally publishedYes

Fingerprint

Cyclooxygenase 2 Inhibitors
Prostaglandin-Endoperoxide Synthases
Observational Studies
Confidence Intervals
Pharmaceutical Preparations
Celecoxib
Anti-Inflammatory Agents
Naproxen
Diclofenac
Myocardial Infarction
Piroxicam
Ibuprofen
Information Storage and Retrieval
Bibliography
Blood Vessels
Meta-Analysis
Case-Control Studies
Cohort Studies

Cite this

@article{4e5fe75978944302a6e898396fbf874b,
title = "Cardiovascular risk and inhibition of cyclooxygenase: A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2",
abstract = "Context: Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older non-selective NSAIDs. Objective: To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors. Data Sources: Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies. Study Selection: Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs. Data Extraction: Two people independently extracted data and assessed study quality with disagreements resolved by consensus. Data Synthesis: Data were combined using a random-effects model. A doserelated risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95{\%} confidence interval [CI], 1.00-1.79) and 2.19 (95{\%} CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95{\%} CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95{\%} CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95{\%} CI, 0.87-1.07); piroxicam, 1.06 (95{\%} CI, 0.70-1.59); and ibuprofen, 1.07 (95{\%} CI, 0.97-1.18). Conclusions: This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.",
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Cardiovascular risk and inhibition of cyclooxygenase : A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. / McGettigan, Patricia; Henry, David.

In: Journal of the American Medical Association, Vol. 296, No. 13, 04.10.2006, p. 1633-1644.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Cardiovascular risk and inhibition of cyclooxygenase

T2 - A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2

AU - McGettigan, Patricia

AU - Henry, David

PY - 2006/10/4

Y1 - 2006/10/4

N2 - Context: Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older non-selective NSAIDs. Objective: To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors. Data Sources: Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies. Study Selection: Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs. Data Extraction: Two people independently extracted data and assessed study quality with disagreements resolved by consensus. Data Synthesis: Data were combined using a random-effects model. A doserelated risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18). Conclusions: This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.

AB - Context: Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older non-selective NSAIDs. Objective: To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors. Data Sources: Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies. Study Selection: Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs. Data Extraction: Two people independently extracted data and assessed study quality with disagreements resolved by consensus. Data Synthesis: Data were combined using a random-effects model. A doserelated risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18). Conclusions: This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.

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U2 - 10.1001/jama.296.13.jrv60011

DO - 10.1001/jama.296.13.jrv60011

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SP - 1633

EP - 1644

JO - Journal of the American Medical Association

JF - Journal of the American Medical Association

SN - 0098-7484

IS - 13

ER -