Two NSAIDs Were Associated With Increase in Heart Risks

The nonsteroidal anti-inflammatory drugs rofecoxib and diclofenac were linked to increased cardiovascular mortality and morbidity in a nationwide cohort of otherwise healthy Danish residents, while naproxen appeared to be associated with the least cardiovascular risk, researchers reported.

Dr. Emil Loldrup Fosbøl of Gentofte University Hospital in Hellerup, Denmark, and colleagues reported that patients in the study taking the nonselective NSAID diclofenac (Voltaren, Cataflam) had a 91% increased risk of cardiovascular death, compared with patients with no NSAID history, and patients taking the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib (Vioxx), which was withdrawn from the market in 2004 because of poor cardiovascular safety, had a 66% increased risk.

The investigators also observed a small, dose-dependent trend for increase in cardiovascular risk associated with ibuprofen, while no such relationship was observed with naproxen, they wrote (Circ. Cardiovasc. Qual. Outcomes 2010 June 8 [doi: 10.1161/CIRC OUTCOMES.109.861104]).

The epidemiologic study included data for 1,028,437 individuals, median age 39, collected from 1997 through 2005. Approximately 45% of the cohort had a history of some NSAID use during this time.

To determine whether specific NSAIDs carried a risk of cardiovascular adverse events, the investigators compared cause-specific mortality and hospitalizations for individuals with and without a history of NSAID use. They estimated the risk of cause-specific death associated with exposure to NSAIDs (ibuprofen, naproxen, diclofenac, rofecoxib, and celecoxib) using two statistical methods: case-crossover and Cox proportional-hazard regression analysis.

In the case-crossover analyses, diclofenac use was associated with a significant increase in the risk of cardiovascular death, coronary death, or nonfatal myocardial infarction, as well as fatal or nonfatal stroke, with a clear dose-dependent relationship, the authors wrote. The dose-dependent association is especially worrying, according to the authors, “because diclofenac more often is used in high doses compared with the other drugs.”

The crossover analyses also showed a significant relationship between rofecoxib treatment and an increased risk of cardiovascular death and the composite of coronary death or nonfatal MI and a nonsignificant trend for increased risk of fatal or nonfatal stroke, while no such relationships were observed for celecoxib (Celebrex), the authors reported. Additionally, high doses of ibuprofen were associated with a significant increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke, they wrote.

In the Cox proportional hazard analysis, diclofenac was linked with increased risk of cardiovascular death in high doses and a dose-dependent increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke; rofecoxib demonstrated a similar but statistically nonsignificant pattern for fatal and nonfatal stroke and an increased risk of coronary death or nonfatal MI and cardiovascular death; and celecoxib showed a “small and statistically insignificant trend” toward increased risk of coronary death, nonfatal MI, and fatal/nonfatal stroke, according to the authors.

Ibuprofen showed a dose-dependent association with coronary and stroke event risk in the Cox analyses, with a decreased risk of coronary death, nonfatal MI, and stroke in low doses and trend for increased risk in high doses, and, as in the crossover analysis, “naproxen was associated with a trend for neutral or decreased risk of all the examined end points,” they wrote.

In repeat analyses conducted on a population of NSAID users and sex-, age-, and time-matched NSAID nonusers, a trend for a higher increase in cardiovascular risk was associated with use of all of the NSAID drugs, the authors reported.

Disclosures: The authors report no financial conflicts relevant to this investigation.

Source Elsevier Global Medical News

The nonsteroidal anti-inflammatory drugs rofecoxib and diclofenac were linked to increased cardiovascular mortality and morbidity in a nationwide cohort of otherwise healthy Danish residents, while naproxen appeared to be associated with the least cardiovascular risk, researchers reported.

Dr. Emil Loldrup Fosbøl of Gentofte University Hospital in Hellerup, Denmark, and colleagues reported that patients in the study taking the nonselective NSAID diclofenac (Voltaren, Cataflam) had a 91% increased risk of cardiovascular death, compared with patients with no NSAID history, and patients taking the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib (Vioxx), which was withdrawn from the market in 2004 because of poor cardiovascular safety, had a 66% increased risk.

The investigators also observed a small, dose-dependent trend for increase in cardiovascular risk associated with ibuprofen, while no such relationship was observed with naproxen, they wrote (Circ. Cardiovasc. Qual. Outcomes 2010 June 8 [doi: 10.1161/CIRC OUTCOMES.109.861104]).

The epidemiologic study included data for 1,028,437 individuals, median age 39, collected from 1997 through 2005. Approximately 45% of the cohort had a history of some NSAID use during this time.

To determine whether specific NSAIDs carried a risk of cardiovascular adverse events, the investigators compared cause-specific mortality and hospitalizations for individuals with and without a history of NSAID use. They estimated the risk of cause-specific death associated with exposure to NSAIDs (ibuprofen, naproxen, diclofenac, rofecoxib, and celecoxib) using two statistical methods: case-crossover and Cox proportional-hazard regression analysis.

In the case-crossover analyses, diclofenac use was associated with a significant increase in the risk of cardiovascular death, coronary death, or nonfatal myocardial infarction, as well as fatal or nonfatal stroke, with a clear dose-dependent relationship, the authors wrote. The dose-dependent association is especially worrying, according to the authors, “because diclofenac more often is used in high doses compared with the other drugs.”

The crossover analyses also showed a significant relationship between rofecoxib treatment and an increased risk of cardiovascular death and the composite of coronary death or nonfatal MI and a nonsignificant trend for increased risk of fatal or nonfatal stroke, while no such relationships were observed for celecoxib (Celebrex), the authors reported. Additionally, high doses of ibuprofen were associated with a significant increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke, they wrote.

In the Cox proportional hazard analysis, diclofenac was linked with increased risk of cardiovascular death in high doses and a dose-dependent increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke; rofecoxib demonstrated a similar but statistically nonsignificant pattern for fatal and nonfatal stroke and an increased risk of coronary death or nonfatal MI and cardiovascular death; and celecoxib showed a “small and statistically insignificant trend” toward increased risk of coronary death, nonfatal MI, and fatal/nonfatal stroke, according to the authors.

Ibuprofen showed a dose-dependent association with coronary and stroke event risk in the Cox analyses, with a decreased risk of coronary death, nonfatal MI, and stroke in low doses and trend for increased risk in high doses, and, as in the crossover analysis, “naproxen was associated with a trend for neutral or decreased risk of all the examined end points,” they wrote.

In repeat analyses conducted on a population of NSAID users and sex-, age-, and time-matched NSAID nonusers, a trend for a higher increase in cardiovascular risk was associated with use of all of the NSAID drugs, the authors reported.

Disclosures: The authors report no financial conflicts relevant to this investigation.

Source Elsevier Global Medical News

The nonsteroidal anti-inflammatory drugs rofecoxib and diclofenac were linked to increased cardiovascular mortality and morbidity in a nationwide cohort of otherwise healthy Danish residents, while naproxen appeared to be associated with the least cardiovascular risk, researchers reported.

Dr. Emil Loldrup Fosbøl of Gentofte University Hospital in Hellerup, Denmark, and colleagues reported that patients in the study taking the nonselective NSAID diclofenac (Voltaren, Cataflam) had a 91% increased risk of cardiovascular death, compared with patients with no NSAID history, and patients taking the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib (Vioxx), which was withdrawn from the market in 2004 because of poor cardiovascular safety, had a 66% increased risk.

The investigators also observed a small, dose-dependent trend for increase in cardiovascular risk associated with ibuprofen, while no such relationship was observed with naproxen, they wrote (Circ. Cardiovasc. Qual. Outcomes 2010 June 8 [doi: 10.1161/CIRC OUTCOMES.109.861104]).

The epidemiologic study included data for 1,028,437 individuals, median age 39, collected from 1997 through 2005. Approximately 45% of the cohort had a history of some NSAID use during this time.

To determine whether specific NSAIDs carried a risk of cardiovascular adverse events, the investigators compared cause-specific mortality and hospitalizations for individuals with and without a history of NSAID use. They estimated the risk of cause-specific death associated with exposure to NSAIDs (ibuprofen, naproxen, diclofenac, rofecoxib, and celecoxib) using two statistical methods: case-crossover and Cox proportional-hazard regression analysis.

In the case-crossover analyses, diclofenac use was associated with a significant increase in the risk of cardiovascular death, coronary death, or nonfatal myocardial infarction, as well as fatal or nonfatal stroke, with a clear dose-dependent relationship, the authors wrote. The dose-dependent association is especially worrying, according to the authors, “because diclofenac more often is used in high doses compared with the other drugs.”

The crossover analyses also showed a significant relationship between rofecoxib treatment and an increased risk of cardiovascular death and the composite of coronary death or nonfatal MI and a nonsignificant trend for increased risk of fatal or nonfatal stroke, while no such relationships were observed for celecoxib (Celebrex), the authors reported. Additionally, high doses of ibuprofen were associated with a significant increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke, they wrote.

In the Cox proportional hazard analysis, diclofenac was linked with increased risk of cardiovascular death in high doses and a dose-dependent increased risk of coronary death or nonfatal MI and fatal or nonfatal stroke; rofecoxib demonstrated a similar but statistically nonsignificant pattern for fatal and nonfatal stroke and an increased risk of coronary death or nonfatal MI and cardiovascular death; and celecoxib showed a “small and statistically insignificant trend” toward increased risk of coronary death, nonfatal MI, and fatal/nonfatal stroke, according to the authors.

Ibuprofen showed a dose-dependent association with coronary and stroke event risk in the Cox analyses, with a decreased risk of coronary death, nonfatal MI, and stroke in low doses and trend for increased risk in high doses, and, as in the crossover analysis, “naproxen was associated with a trend for neutral or decreased risk of all the examined end points,” they wrote.

In repeat analyses conducted on a population of NSAID users and sex-, age-, and time-matched NSAID nonusers, a trend for a higher increase in cardiovascular risk was associated with use of all of the NSAID drugs, the authors reported.

Disclosures: The authors report no financial conflicts relevant to this investigation.

Source Elsevier Global Medical News