SUNDAY, Nov. 13, 2005 (HealthDay News) -- Taking pain relievers called non-steroidal anti-inflammatory drugs (NSAIDs) -- including Cox-2 inhibitors such as Celebrex -- after a heart attack increases the risk of death, a new Danish study has found.
The higher the dose, the higher the risk of death, according to research presented Sunday at the American Heart Association's scientific sessions 2005 in Dallas.
The study did not include aspirin, which is known to benefit patients after a heart attack. Nor did the study find any link between NSAIDs and a second heart attack.
In light of the steadily increasing and often confusing body of information related to certain NSAIDs and cardiovascular risks, how are consumers to take this additional information?
"The results of our study should be viewed along with the rest of the evidence," said Dr. Gunnar H. Gislason, lead author of the study and a research fellow at Bispebjerg University Hospital in Copenhagen, Denmark. "Patients with a previous myocardial infarction (heart attack) should, if at all possible, avoid high-dose NSAID and Cox-2 inhibitors at any dose. Patients with severe pain that can be relieved by these drugs may choose to be treated, but they need to discuss the balance between benefit and risk carefully with their doctors."
Dr. Mark Fendrick, professor of internal medicine at the University of Michigan School of Medicine, added: "This large, observational study adds to the mounting evidence that Cox-2 selective and traditional NSAIDs may lead to increased all-cause mortality rates. This hypothesis-generating investigation, when put alongside other retrospective analyses, warrants the performance of randomized, controlled investigations to more definitively quantify the risks of NSAIDs, while providing better insight into the not-well-understood mechanisms behind these adverse events."
NSAIDs are pain relievers -- including aspirin, ibuprofen and naproxen -- that carry a risk of gastrointestinal bleeding. Cox-2 inhibitors are a specific type of NSAID that do not carry this risk.
Cox-2 inhibitors and NSAIDs have been caught in a prolonged furor since September 2004 when Vioxx was withdrawn from the market due to concerns about cardiovascular safety. Similar concerns were raised about Bextra, another Cox-2, then Celebrex, and then naproxen, a traditional NSAID. Bextra was later withdrawn from the market.
A number of studies continue to look at the different risks and benefits of the drugs. This study is the first to look at patients who took NSAIDs after suffering their first heart attack.
The researchers analyzed records of 58,432 men and women in the Danish National Patients Registry who had been discharged from hospital care between 1995 and 2002 after a first acute heart attack.
Compared with people not taking NSAIDs, men and women taking more than 200 milligrams a day of Celebrex (celecoxib) had a 4.24 times higher chance of death; those taking more than 25 milligrams a day of Vioxx (rofecoxib) had a 5.03 times higher risk; those taking more than 100 milligrams a day of Cataflam and Voltaren (diclofenac) had a 3.76 times higher risk; and those taking other NSAIDs had a 1.22 times higher chance of dying. The risk of death was 1.96 times higher for people taking more than 1,200 milligrams a day of ibuprofen, such as Advil or Motrin.
Lower doses of Celebrex and Vioxx also showed a higher risk of death, although not lower doses of ibuprofen or diclofenac.
Oddly, there was no increased risk of a second heart attack, and the researchers are still trying to figure out if there were any patterns in the causes of death.
"Cox-2 inhibitors are associated with a substantial increase in the risk of death and more so with higher doses," Gislason said. "NSAIDs are associated with an increased risk of death in high doses, but not in low doses."
According to Gislason, this is not the end of the story.
"The studies in this field have revealed that major safety concerns were present where none were expected," he said. "In our view, the safety of not only COX-2 inhibitors, but also that of all NSAIDs, need to be addressed."
The American Heart Association has a statement on pain medications.