People who take some commonly prescribed painkillers for arthritis are at greater risk of developing congestive heart failure, new Canadian research suggests.
The findings could have broad repercussions because one in four seniors currently takes these drugs.
The bestseller, Vioxx, increased the risk of hospitalization for heart failure by 80 per cent within one year of prescription.
Taking a non-steroidal anti-inflammatory drug, such as ibuprofen or naproxen, increased the risk by about 10 per cent. Taking Celebrex, another bestseller, did not increase the risk of hospitalization for heart failure, researchers found.
However, among patients already suffering from heart failure, all the painkillers increased risk substantially, suggesting they exacerbate existing problems.
"The message we should retain is that there are definitely risks associated with taking these drugs, along with the benefits," said Muhammad Mamdani, a senior scientist at the Toronto-based Institute for Clinical Evaluative Sciences, which conducted the study.
He said that, overall, only about 1 per cent of seniors taking these painkillers are hospitalized for congestive heart failure each year, but given the large number of patients treated, "these results are clinically important and suggest a need for careful monitoring of the cardiovascular effects on patients receiving them."
The findings were published in today's edition of the medical journal The Lancet.
The principal drugs analyzed in this study, Vioxx and Celebrex, are among the most successful and profitable prescription drugs in history. Launched with much fanfare in 1999, they have largely displaced cheaper painkillers used to treat arthritis, though they are only marginally more effective.
They are both cyclo-oxygenase-2 inhibitors, meaning they inhibit production of cox-2, an enzyme involved in pain and inflammation. The non-steroidal anti-inflammatory drugs do the same, but in a less specific manner. (The study did not look at the effects of taking acetylsalicylic acid, or Aspirin, for arthritis.)
The drugs also increase blood pressure, which is likely why the risk of heart failure rises.
The main selling point of cox-2 inhibitors is that they cause fewer gastrointestinal problems than the traditional anti-inflammatory drugs.
Dr. Mamdani said it is "really ironic" that patients may be trading one side effect, gastric bleeding, for a far more serious one, congestive heart failure. He also noted that the number of gastric bleeds and ulcers has probably increased because so many more people are taking drugs to treat arthritis than before the new drugs were launched.
About one in five people over the age of 65 takes cox-2 inhibitors, and about one in three takes the traditional anti-inflammatory painkillers.
Based on the emerging evidence of risks, physicians and patients alike should rethink this sort of ubiquitous use, said Dr. Mamdani, who is also an assistant professor in the department of pharmacy at the University of Toronto.
"While these drugs have been greeted with great enthusiasm, perhaps more judicious prescribing by physicians is warranted," he said.
The researcher also recommended that arthritis sufferers "have a serious discussion with their physician before considering these drugs," particularly if they have a history of cardiovascular disease or gastrointestinal problems.
The new research is based on an analysis of patient records of almost 45,000 Ontario patients who were prescribed cox-2 inhibitors or non-steroidal anti-inflammatory drugs between April, 2000, and March, 2001. They were compared to 100,000 others who were not prescribed these drugs. The average age of those in the study was 75, a population that has high rates of osteoarthritis and heart failure.
There were 7.7 million prescriptions for cox-2 inhibitors in Canada last year (including almost three million for Celebrex and 3.3 million for Vioxx), with a total value of $475-million, according to IMS Health Canada, a private company that tracks prescription-drug use. There were 16 million prescriptions for the non-steroidal anti-inflammatories, with sales totalling $305-million.
About four million Canadians suffer from arthritis. Approximately 350,000 have congestive heart failure.
Dr. Mamdani said earlier research helps explain why Vioxx users are more likely to develop heart failure than Celebrex users. In head-to-head comparisons, Vioxx raised blood pressure more than Celebrex. Vioxx also has a longer half-life, meaning it stays in the body longer, and it has a tendency to accumulate.
The researcher said patients should not stop taking their prescription drugs based on this study. Rather, Dr. Mamdani said, if a person has concerns, the matter should be discussed with his or her physician to determine the personal risk and benefits from taking a particular drug.