Features April 2003 Issue

Is Your Painkiller Putting You In Danger Of A Heart Attack?

The jury is out, but this we know: Choosing the right

Afew years ago, physicians became encouraged when two new drugs, Celebrex and Vioxx—COX-1 and COX-2 inhibitors, called “coxibs”—became available for arthritis sufferers. Your doctor may well have prescribed these drugs for you, since they markedly reduce the risk of stomach ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs) like Motrin (ibuprofen) and Naprosyn (naproxen). This was important because almost 110,000 patients are hospitalized and 16,500 die every year in the U.S. due to NSAID-related ulcer complications.

But new studies suggest that coxibs can increase your risk of heart disease. Says Dr. Daniel Mazanec, a rheumatologist and director of the Spine Center at the Cleveland Clinic, “We thought coxibs were the answer to one of the most frustrating and dangerous complications we’re confronted with in managing pain.”

Coxibs Reduce Ulcer Risk, But…
“In this regard,” says Dr. Mazanec, “we weren’t disappointed—coxibs certainly cause fewer ulcers, but new research has raised new questions.”

A clinical trial called VIGOR (Vioxx Gastrointestinal Outcomes Research) was the first to question the safety of coxibs. In this study, patients took Vioxx or the NSAID Naprosyn, which is similar to aspirin in its blood-thinning properties. As expected, half as many patients who were on Vioxx than those who were on Naprosyn developed some type of ulcer. However, more than twice as many strokes or heart attacks occurred among patients in the Vioxx group than among those taking Naprosyn. Although few patients in the trial experienced these outcomes, the difference was statistically significant and therefore troubling.

What We Know Now
The VIGOR results could be explained in two ways: 1) Vioxx increased the risk of stroke or heart attack because of its inability to protect against blood clotting, or 2) Naprosyn decreased the risk of stroke or heart attack because of its aspirin-like blood-thinning effect. Unfortunately, doctors couldn’t determine which explanation was the correct one. Another study showed that another coxib, Celebrex, and low doses of Vioxx (25 mg or less) do not increase heart disease risk, while only the highest approved dose of Vioxx (50 mg) increased the risk. Other studies suggested that Naprosyn, like aspirin, decreased the risk of heart disease.

Some researchers thought that the way coxibs and NSAIDs work might explain the results. In blood there’s a balance between substances made by enzymes in cells in the blood and in the blood vessel wall that either prevent or stimulate blood clotting. Since blood clots can cause heart attacks, it’s best not to upset this balance. Coxibs do little to prevent blood clotting—or, to put that another way, they shift the balance in favor of blood clotting. NSAIDs neither prevent nor stimulate blood clotting, so they do not upset the balance.

The same enzymes affected by coxibs and NSAIDs in blood cells and the blood vessel wall also reside in the kidney, which, besides filtering your blood, helps control your blood pressure. Researchers believe that by inhibiting these enzymes through the use of coxibs (which can increase blood pressure and may cause swelling [edema]), changes are brought about that increase the risk of heart disease and kidney failure.

These results, physicians agree, need to be sorted out with further studies. Meanwhile, doctors still must prescribe painkillers for their patients—determining their patients’ risk factors for heart and kidney disease, then choosing a painkiller that minimizes the increase in risk.

Individualized Treatment A Must
If a patient is at risk of heart disease and requires coxibs for the treatment of arthritis pain, low-dose aspirin is indicated and should be used because neither coxibs nor NSAIDs can provide the same protective benefit. Further, says Dr. Mazanec, “Low-dose aspirin does not appear to negate the ulcer-risk-reducing benefits of coxibs.” Patients at high risk for ulcers should also take a drug that prevents ulcers at the same time. Patients with kidney impairment, or those taking drugs for high blood pressure that affect kidney function, risk additional kidney injury with coxibs and NSAIDs, so they should be monitored closely. These painkillers should be discontinued if any increase in blood pressure or signs of impaired kidney function are seen. Low-dose acetaminophen (Tylenol) is a possible alternative. Patients without risk factors for heart or kidney disease should do well on one of the coxibs in order to take advantage of their protective effects on the stomach.