Large Study Shows a New Cox-2 Inhibitor is Safe for the Heart

NYU School of Medicine Researcher Who Led the Study Comments on the Results

NEW YORK, August 19, 2004 -- A new painkiller, a member of the Cox-2 inhibitor family of drugs, can be used safely in arthritis patients at risk for heart attacks, says Michael Farkouh, M.D., a cardiologist at NYU School of Medicine, who led a new study on the drug's effects on the heart. However, he notes, the study does not resolve all concerns about Cox-2 inhibitors.

The two-part study, published in the August 21, 2004, issue of The Lancet, a British medical journal, evaluates the painkiller in more than 18,000 arthritis patients. It assesses its impact on the heart and the stomach compared to older types of painkillers. The new drug is not yet approved for marketing by the Food and Drug Administration. 

"The fact that we enrolled osteoarthritis patients in the study who already had high blood pressure or other risk factors for coronary heart disease like high cholesterol was incredibly important," says Dr. Farkouh, Director of the Cardiac Care Unit and Assistant Professor of Medicine in the Leon H. Charney Division of Cardiology at NYU School of Medicine.

"As a cardiologist, many of my patients have osteoarthritis," says Dr. Farkouh. "Until we had the results of this study," he notes, "I was afraid to prescribe a Cox-2 inhibitor to relieve their pain and get them moving so that they could improve their cardiac function. Now I feel more confident in prescribing this class of drugs."    

It still remains to be determined whether Cox-2 inhibitors can be used safely in patients who have already suffered a heart attack or stroke, says Dr. Farkouh.

Cox-2 inhibitors relieve pain and inflammation to the same extent as aspirin and other over-the-counter painkillers such as ibuprofen, but unlike aspirin and the other drugs they do not damage the lining of the stomach.

The ability to safeguard the stomach is a benefit. However, several years ago concerns started to emerge about effects of Cox-2 inhibitors on the heart. In a widely read study published in 2001, researchers reviewed two major trials and reported that Cox-2 inhibitors were associated with a significantly higher risk of heart attack than naproxen, another type of painkiller. However, the number of actual heart attacks in the trials under review was small. Consequently, there was no way to really determine the magnitude of the risk.

The latest study, an international, multicenter effort should contribute greatly to understanding that magnitude, says Dr. Farkouh. The study, called TARGET for The Therapeutic Arthritis Research and Gastrointestinal Event Trial, involved a Cox-2 inhibitor called lumiracoxib, which is made by the drug company Novartis. The company paid for the study; Dr. Farkouh has no financial interest in the company and he was part of an independent committee that designed the cardiovascular portion of the study and monitored its results.

The study is a large and randomized clinical trial, the so-called "gold standard" used by scientists to objectively evaluate a treatment's affects. It is "prospective," meaning that patients were randomly assigned to a specific medication regimen and then followed over a period of time. And, the trial enrolled 18,325 patients who reflected the general population of osteoarthritis sufferers age 50 and older, meaning that they had a high incidence of high blood pressure or a previous history of vascular disease or other problems such as diabetes.

In the trial, patients took 400 milligrams of lumiracoxib once daily, or 500 milligrams of naproxen twice daily, or 800 milligrams of ibuprofen three times a day for 52 weeks.  Some 24 percent of all patients in the study took low-dose aspirin in addition to the other painkiller. Most of the patients taking aspirin were at increased risk for coronary heart disease.  Aspirin inhibits the formation of blood clots and is widely used to help reduce the risk of heart attacks.

     According to the results of the study, the patients taking the Cox-2 inhibitor, regardless of whether they were also taking aspirin, did not experience significantly more heart attacks, strokes, or episodes of high blood pressure compared to patients taking the naproxen or the ibuprofen.  Moreover, there was practically no difference in the number of heart attacks among those taking the lumiracoxib and aspirin compared with those taking the ibuprofen or the naproxen and aspirin.

     "Our study doesn't resolve every question about Cox-2 inhibitors because of the small number of cardiac events in our study, but overall these drugs don't appear to be a significant health problem," says Dr. Farkouh.