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Selective COX-2 inhibitors, NSAIDs and cardiovascular events - is celecoxib the safest choice?

Howes LG - Ther Clin Risk Manag (2007)

Bottom Line: However, subsequent data have suggested an association between therapy with non-selective COX inhibitors (NSAIDs) and serious cardiovascular events.Celecoxib therapy may be associated with an increased risk of cardiovascular events, but only when used at doses substantially higher than those recommended for the treatment of arthritis.There is a greater body of evidence supporting the relative cardiovascular safety of celecoxib when used at the doses recommended for the treatment of arthritis than for any of the other selective COX-2 inhibitors or NSAIDs.

View Article: PubMed Central - PubMed

Affiliation: Departments of Cardiology, and Pharmacology and Therapeutics, Gold Coast Hospital, Griffith University Medical School Southport, Queensland, Australia.

ABSTRACT
Inhibitors of cyclo-oxogenase (COX) are widely used anti-inflammatory drugs. In recent years concerns have arisen about the cardiovascular safety of these drugs, initially because of reported associations between therapy with the COX-2 selective inhibitor rofecoxib and myocardial infarction. However, subsequent data have suggested an association between therapy with non-selective COX inhibitors (NSAIDs) and serious cardiovascular events. This article reviews the clinical trial and population data linking COX inhibition to cardiovascular events. The data currently available suggests that both specific and non-specific COX inhibitors may increase the risk of serious cardiovascular events, but that the effect varies between the individual drugs. The strongest evidence for an increased risk of serious cardiovascular events is with rofecoxib therapy. Celecoxib therapy may be associated with an increased risk of cardiovascular events, but only when used at doses substantially higher than those recommended for the treatment of arthritis. There is a greater body of evidence supporting the relative cardiovascular safety of celecoxib when used at the doses recommended for the treatment of arthritis than for any of the other selective COX-2 inhibitors or NSAIDs.

No MeSH data available.


Related in: MedlinePlus

Cumulative incidence of cardiovascular events on rofecoxib and placebo therapy in the APPROVe Study.
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Related In: Results  -  Collection


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fig1: Cumulative incidence of cardiovascular events on rofecoxib and placebo therapy in the APPROVe Study.

Mentions: The APPROVe study was a 3-year, placebo-controlled study of rofecoxib 25 mg daily in the prevention of adenomatous colonic polyps (Bresalier et al 2005). The study enrolled 2586 patients with a history of colorectal adenoma, 1287 of whom received rofecoxib 25 mg daily and 1299 of whom received placebo. Patients with a history of ischemic heart disease or cerebrovascular disease were excluded. Monitoring of cardiovascular events was a planned component of the trial. Potential cardiovascular endpoints were adjudicated in a blinded manner. Serious adverse cardiovascular events were defined as fatal and non-fatal myocardial infarction, unstable angina, sudden death from cardiac causes, fatal and non-fatal ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, peripheral venous thrombosis, and pulmonary embolism. The patients were followed for approximately three years (3059 patient-years). After about 18 months of therapy a statistically significant difference in cardiovascular events was found between the patients receiving rofecoxib and those receiving placebo (Figure 1). Forty five patients receiving rofecoxib experienced a serious cardiovascular thromboembolic event compared to 25 of the patients receiving placebo (relative risk 1.92, 95% confidence intervals 1.19 to 3.11, P = 0.008). Major contributors to the excess number of cardiovascular events in patients receiving rofecoxib were myocardial infarction (21 on rofecoxib verses 9 on placebo) and ischemic stroke (11 verses 6). These findings led the manufacturer Merck Pty Ltd to voluntarily withdraw the drug from marketing at the beginning of October 2004. A significantly greater number of patients developed hypertension on rofecoxib therapy than on placebo (14.3% verses 7.3%), a factor which could have contributed to the higher incidence of cardiovascular events on rofecoxib therapy.


Selective COX-2 inhibitors, NSAIDs and cardiovascular events - is celecoxib the safest choice?

Howes LG - Ther Clin Risk Manag (2007)

Cumulative incidence of cardiovascular events on rofecoxib and placebo therapy in the APPROVe Study.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376081&req=5

fig1: Cumulative incidence of cardiovascular events on rofecoxib and placebo therapy in the APPROVe Study.
Mentions: The APPROVe study was a 3-year, placebo-controlled study of rofecoxib 25 mg daily in the prevention of adenomatous colonic polyps (Bresalier et al 2005). The study enrolled 2586 patients with a history of colorectal adenoma, 1287 of whom received rofecoxib 25 mg daily and 1299 of whom received placebo. Patients with a history of ischemic heart disease or cerebrovascular disease were excluded. Monitoring of cardiovascular events was a planned component of the trial. Potential cardiovascular endpoints were adjudicated in a blinded manner. Serious adverse cardiovascular events were defined as fatal and non-fatal myocardial infarction, unstable angina, sudden death from cardiac causes, fatal and non-fatal ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, peripheral venous thrombosis, and pulmonary embolism. The patients were followed for approximately three years (3059 patient-years). After about 18 months of therapy a statistically significant difference in cardiovascular events was found between the patients receiving rofecoxib and those receiving placebo (Figure 1). Forty five patients receiving rofecoxib experienced a serious cardiovascular thromboembolic event compared to 25 of the patients receiving placebo (relative risk 1.92, 95% confidence intervals 1.19 to 3.11, P = 0.008). Major contributors to the excess number of cardiovascular events in patients receiving rofecoxib were myocardial infarction (21 on rofecoxib verses 9 on placebo) and ischemic stroke (11 verses 6). These findings led the manufacturer Merck Pty Ltd to voluntarily withdraw the drug from marketing at the beginning of October 2004. A significantly greater number of patients developed hypertension on rofecoxib therapy than on placebo (14.3% verses 7.3%), a factor which could have contributed to the higher incidence of cardiovascular events on rofecoxib therapy.

Bottom Line: However, subsequent data have suggested an association between therapy with non-selective COX inhibitors (NSAIDs) and serious cardiovascular events.Celecoxib therapy may be associated with an increased risk of cardiovascular events, but only when used at doses substantially higher than those recommended for the treatment of arthritis.There is a greater body of evidence supporting the relative cardiovascular safety of celecoxib when used at the doses recommended for the treatment of arthritis than for any of the other selective COX-2 inhibitors or NSAIDs.

View Article: PubMed Central - PubMed

Affiliation: Departments of Cardiology, and Pharmacology and Therapeutics, Gold Coast Hospital, Griffith University Medical School Southport, Queensland, Australia.

ABSTRACT
Inhibitors of cyclo-oxogenase (COX) are widely used anti-inflammatory drugs. In recent years concerns have arisen about the cardiovascular safety of these drugs, initially because of reported associations between therapy with the COX-2 selective inhibitor rofecoxib and myocardial infarction. However, subsequent data have suggested an association between therapy with non-selective COX inhibitors (NSAIDs) and serious cardiovascular events. This article reviews the clinical trial and population data linking COX inhibition to cardiovascular events. The data currently available suggests that both specific and non-specific COX inhibitors may increase the risk of serious cardiovascular events, but that the effect varies between the individual drugs. The strongest evidence for an increased risk of serious cardiovascular events is with rofecoxib therapy. Celecoxib therapy may be associated with an increased risk of cardiovascular events, but only when used at doses substantially higher than those recommended for the treatment of arthritis. There is a greater body of evidence supporting the relative cardiovascular safety of celecoxib when used at the doses recommended for the treatment of arthritis than for any of the other selective COX-2 inhibitors or NSAIDs.

No MeSH data available.


Related in: MedlinePlus