Even Short-Term NSAID Use Raises Death/Recurrent MI Risk

For patients with a history of myocardial infarction, any length of treatment with nonsteroidal anti-inflammatory drugs poses an unacceptably high risk for death or recurrent heart attack, based on findings from a Danish study using hospital and pharmacy registry data and published online May 9 in Circulation.

The risk elevation began during the first week of therapy and continued throughout the course of treatment, with some differences in the magnitude of risk between NSAIDs.

"These results challenge the view that NSAIDs are not harmful during short-term [1-week] treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established cardiovascular disease is required," concluded Anne-Marie Schjerning of the department of cardiology, Copenhagen University Hospital in Gentofte, Denmark, and her coauthors. (Circulation 2011 May 9 [doi: 0.1161/CIRCULATIONAHA.110.004671]).

The significant increase in death and recurrent myocardial infarction associated with the use of NSAIDs in a study of people with a history of myocardial infarction indicates that current recommendations regarding NSAID use in patients with cardiovascular disease need to be revised, the study authors concluded.

Although international guidelines state that NSAID use should be discouraged in people with established cardiovascular disease, they say that if such use is unavoidable, the duration of NSAID treatment "should be as short as possible," the authors pointed out.

The investigators conducted the study to address the paucity of information on the association between the duration of treatment with NSAIDs and the risk of cardiovascular disease, in this population of patients. Of the 83,675 people aged 30 years and older who had had their first MI from 1997 through 2006 identified in the national registries (mean age, 68 years), 42% had received NSAIDs.

Overall, treatment with NSAIDs was associated with a 45% greater risk of death/recurrent MI during the first 7 days of treatment, which persisted and was increased by 65% over a 30- to 90-day period of treatment.

The greatest risk identified was with diclofenac (hazard ratio, 3.26; 95% confidence interval, 2.57-3.86 for death/MI at day 1-7 of treatment). Diclofenac is available over the counter in many countries, the authors noted.

A significant increase in risk was seen after 1 week of treatment with ibuprofen, in the first week of treatment with rofecoxib (which has been withdrawn from the market), and after 14-30 days with celecoxib. The risk associated with ibuprofen was lower than the risk associated with the two cyclo-oxygenase-2 (COX-2) selective inhibitors, rofecoxib and celecoxib, and it was lower than the risk associated with the use of diclofenac. There was no increased risk of death or recurrent MI associated with naproxen for the entire treatment duration, which exceeded 90 days in some cases. However, naproxen has been associated with an increased risk of GI bleeding, compared with rofecoxib, in one study, the authors noted.

The results of the study "challenge" American Heart Association recommendations regarding NSAID treatment in patients with established cardiovascular disease "because we demonstrate that even short-term NSAID treatment is associated with increased cardiovascular risk in patients with prior MI," the authors stressed.

Despite some limitations of the study, namely the observational design and the possible effects of information bias, and the need for randomized clinical studies, the investigators added: "The accumulating evidence suggests that we must limit NSAID use to the absolute minimum in patients with established cardiovascular disease."

The authors said they had no relevant financial disclosures.

For patients with a history of myocardial infarction, any length of treatment with nonsteroidal anti-inflammatory drugs poses an unacceptably high risk for death or recurrent heart attack, based on findings from a Danish study using hospital and pharmacy registry data and published online May 9 in Circulation.

The risk elevation began during the first week of therapy and continued throughout the course of treatment, with some differences in the magnitude of risk between NSAIDs.

"These results challenge the view that NSAIDs are not harmful during short-term [1-week] treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established cardiovascular disease is required," concluded Anne-Marie Schjerning of the department of cardiology, Copenhagen University Hospital in Gentofte, Denmark, and her coauthors. (Circulation 2011 May 9 [doi: 0.1161/CIRCULATIONAHA.110.004671]).

The significant increase in death and recurrent myocardial infarction associated with the use of NSAIDs in a study of people with a history of myocardial infarction indicates that current recommendations regarding NSAID use in patients with cardiovascular disease need to be revised, the study authors concluded.

Although international guidelines state that NSAID use should be discouraged in people with established cardiovascular disease, they say that if such use is unavoidable, the duration of NSAID treatment "should be as short as possible," the authors pointed out.

The investigators conducted the study to address the paucity of information on the association between the duration of treatment with NSAIDs and the risk of cardiovascular disease, in this population of patients. Of the 83,675 people aged 30 years and older who had had their first MI from 1997 through 2006 identified in the national registries (mean age, 68 years), 42% had received NSAIDs.

Overall, treatment with NSAIDs was associated with a 45% greater risk of death/recurrent MI during the first 7 days of treatment, which persisted and was increased by 65% over a 30- to 90-day period of treatment.

The greatest risk identified was with diclofenac (hazard ratio, 3.26; 95% confidence interval, 2.57-3.86 for death/MI at day 1-7 of treatment). Diclofenac is available over the counter in many countries, the authors noted.

A significant increase in risk was seen after 1 week of treatment with ibuprofen, in the first week of treatment with rofecoxib (which has been withdrawn from the market), and after 14-30 days with celecoxib. The risk associated with ibuprofen was lower than the risk associated with the two cyclo-oxygenase-2 (COX-2) selective inhibitors, rofecoxib and celecoxib, and it was lower than the risk associated with the use of diclofenac. There was no increased risk of death or recurrent MI associated with naproxen for the entire treatment duration, which exceeded 90 days in some cases. However, naproxen has been associated with an increased risk of GI bleeding, compared with rofecoxib, in one study, the authors noted.

The results of the study "challenge" American Heart Association recommendations regarding NSAID treatment in patients with established cardiovascular disease "because we demonstrate that even short-term NSAID treatment is associated with increased cardiovascular risk in patients with prior MI," the authors stressed.

Despite some limitations of the study, namely the observational design and the possible effects of information bias, and the need for randomized clinical studies, the investigators added: "The accumulating evidence suggests that we must limit NSAID use to the absolute minimum in patients with established cardiovascular disease."

The authors said they had no relevant financial disclosures.

For patients with a history of myocardial infarction, any length of treatment with nonsteroidal anti-inflammatory drugs poses an unacceptably high risk for death or recurrent heart attack, based on findings from a Danish study using hospital and pharmacy registry data and published online May 9 in Circulation.

The risk elevation began during the first week of therapy and continued throughout the course of treatment, with some differences in the magnitude of risk between NSAIDs.

"These results challenge the view that NSAIDs are not harmful during short-term [1-week] treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established cardiovascular disease is required," concluded Anne-Marie Schjerning of the department of cardiology, Copenhagen University Hospital in Gentofte, Denmark, and her coauthors. (Circulation 2011 May 9 [doi: 0.1161/CIRCULATIONAHA.110.004671]).

The significant increase in death and recurrent myocardial infarction associated with the use of NSAIDs in a study of people with a history of myocardial infarction indicates that current recommendations regarding NSAID use in patients with cardiovascular disease need to be revised, the study authors concluded.

Although international guidelines state that NSAID use should be discouraged in people with established cardiovascular disease, they say that if such use is unavoidable, the duration of NSAID treatment "should be as short as possible," the authors pointed out.

The investigators conducted the study to address the paucity of information on the association between the duration of treatment with NSAIDs and the risk of cardiovascular disease, in this population of patients. Of the 83,675 people aged 30 years and older who had had their first MI from 1997 through 2006 identified in the national registries (mean age, 68 years), 42% had received NSAIDs.

Overall, treatment with NSAIDs was associated with a 45% greater risk of death/recurrent MI during the first 7 days of treatment, which persisted and was increased by 65% over a 30- to 90-day period of treatment.

The greatest risk identified was with diclofenac (hazard ratio, 3.26; 95% confidence interval, 2.57-3.86 for death/MI at day 1-7 of treatment). Diclofenac is available over the counter in many countries, the authors noted.

A significant increase in risk was seen after 1 week of treatment with ibuprofen, in the first week of treatment with rofecoxib (which has been withdrawn from the market), and after 14-30 days with celecoxib. The risk associated with ibuprofen was lower than the risk associated with the two cyclo-oxygenase-2 (COX-2) selective inhibitors, rofecoxib and celecoxib, and it was lower than the risk associated with the use of diclofenac. There was no increased risk of death or recurrent MI associated with naproxen for the entire treatment duration, which exceeded 90 days in some cases. However, naproxen has been associated with an increased risk of GI bleeding, compared with rofecoxib, in one study, the authors noted.

The results of the study "challenge" American Heart Association recommendations regarding NSAID treatment in patients with established cardiovascular disease "because we demonstrate that even short-term NSAID treatment is associated with increased cardiovascular risk in patients with prior MI," the authors stressed.

Despite some limitations of the study, namely the observational design and the possible effects of information bias, and the need for randomized clinical studies, the investigators added: "The accumulating evidence suggests that we must limit NSAID use to the absolute minimum in patients with established cardiovascular disease."

The authors said they had no relevant financial disclosures.