In the largest study of its kind, Canadian researchers have found that a COX-2 inhibitor had neither favorable nor adverse affects on blood vessel function in people with coronary artery disease. There has been considerable debate lately as to whether these drugs possess heart protective benefits in addition to their role in treating arthritis pain.Researchers at the Queen Elizabeth II Health Sciences Centre in Halifax, Novia Scotia, Canada studied the drug Vioxx — which is in the same class of COX-2 inhibitors as Celebrex and Bextra — and found that it had similar effects on vascular function and inflammation as a placebo.
The study was published in the November 19th issue of the Journal of the American College of Cardiology.
Dr. Lawrence Title and colleagues studied 60 patients who were managing their coronary artery disease with ACE inhibitors and lipid lowering drugs. In addition to taking 325 milligrams of aspirin once a day, the study participants were randomized to receive 25 milligrams of Vioxx or a sugar pill for 8 weeks.
The patients were evaluated for vascular function by measuring blood flow through the brachial artery when a pressure cuff was applied and after nitroglycerin pills were given. Blood samples were also analyzed to measure cholesterol levels and markers of inflammation, including C-reactive protein—a powerful predictor of heart attack and stroke.
Although flow-mediated dilation—a measure of blood vessel function—tended to be higher in the Vioxx group, analysis of the data showed it did not significantly change in either group. The researchers also found that lipid levels and circulating levels of inflammatory markers, such as C-reactive protein, were not altered in either placebo or Vioxx patients.
An earlier, but much smaller study on the drug Celebrex showed that the COX-2 inhibitor did improve flow-mediated dilation and lowered C-reactive protein levels. But the researchers of the Vioxx study write, "it remains unknown whether such differences exist among the various selective COX-2 inhibitors."
The debate among researchers as to whether these drugs have a protective or deleterious effect on the heart centers on the fact that COX-2 enzyme expression is elevated within atherosclerotic lesions, or plaque, along blood vessels. Thus, some believe blocking COX-2 may inhibit inflammation and progression of atherosclerosis.
Conversely, others say there is evidence to suggest the presence of COX-2 in plaque has a protective role by maintaining the balance of specific chemicals that favor an anti-thrombotic state within the vessel.
Dr. Title and his colleagues say it’s possible they were unable to observe a difference between placebo and control groups because Vioxx may have its effects "at the cellular level, which are not detectible by measuring flow-mediated function and nonspecific serum inflammatory markers."
They also point out "that the concomitant use of low-dose aspirin, statins, and ACE inhibitors may have suppressed the levels of those markers within the normal range."
In the same issue of the Journal, an editorial by Dr. Subodh Verma and Paul Szmitko, BSc stated, "it is important to realize that until a large-scale randomized controlled trial with hard endpoints (heart attack, stroke, and cardiovascular death) is conducted we will not have definitive answers as to whether coxibs (COX-2 inhibitors) are neutral, promote atherothrombosis, or are actually antiatherogenic (heart protective)."
The editorial went on to say that this study on Vioxx in patients with coronary artery disease is an important addition to the research on COX-2 inhibitors.
