Hypertension, Diabetes Connection

The Celecoxib Rofecoxib Efficacy and Safety in Comorbodities Evaluation Trial (CRESCENT) evaluated the effects of the COX-2 inhibitors and naproxen on 24-hour blood pressure readings in patients with type 2 diabetes, hypertension, and osteoarthritis.

"Reductions in osteoarthritis symptoms, including pain, mobility, and stiffness, were similar in all treatment groups," the researchers found. "The mean (average) 24-hour systolic [top number in blood pressure reading] blood pressure following 6-weeks of therapy was increased significantly by refecoxib but not by celecoxib or naproxen."

"[T]hese results suggest the need for careful monitoring and control of blood pressure when NSAIDS (non-steroidal anti-inflammatory drugs) or COX-2 inhibitors are chosen for osteoarthritis management for patients with hypertension and type 2 diabetes and further suggest need for careful evaluation of currently available as well as future COX-2-specific inhibitors and nonspecific NSAIDs in this population," the authors conclude.

COX-2 versus Nonnaproxen NSAIDs

An observational study of 6,250 patients enrolled in the Maryland Medicaid program found that COX-2 inhibitors did not increase the risk for cardiovascular events over nonnaproxen NSAIDs in a high-risk population.

The authors conclude: "The results of this analysis do not show a difference in the rate of cardiovascular events between COX-2 inhibitors and nonnaproxen NSAIDs. Given that the study population had higher baseline cardiovascular risk, these observations provide more confidence that the widespread use of COX-2 inhibitors will not be associated with an increase in thrombotic or coronary artery events. This is particularly important because NSAIDs are often used in older, higher-risk patients."

Hemorrhage Risk with Warfarin

Patients taking warfarin at the same time as selective COX-2 inhibitors or nonselective NSAIDs have an increased risk of hospitalization for upper gastrointestinal (GI) hemorrhage, according to Canadian researchers analyzing health care databases. Warfarin is an anti-coagulant (blood thinner used to prevent clots) commonly used in patients with a variety of thromboembolic [blood vessel blocking, usually by a clot] condition.

"Our findings suggest that the risk of upper GI hemorrhage is similarly heighted in warfarin users treated with either selective COX-2 inhibitors or nonselective NSAIDs," the authors write.

"[P]hysicians and pharmacists who care for elderly patients taking warfarin should be aware of the potential risks of concomitant therapy with NSAIDs or COX-2 inhibitors, particularly because the latter are among the fastest-growing class of prescription medications and have rapidly gained acceptance in clinical practice."

Current Surveillance System Does Not Work

In an editorial accompanying all of the studies, Daniel H. Solomon, M.D., M.P.H., from Brigham and Women's Hospital, Boston, and Jerry Avorn, M.D., of Harvard University School of Medicine, write that the withdrawal of rofecoxib (Vioxx) from the market in September 2004 by its manufacturer, Merck & Co., "raises many questions concerning drug policy, scientific evidence, and treatment alternatives. Several of these questions are raised by articles in this issue of the Archives."

"Several lessons can be learned from the 5-year experience and eventual withdrawal of rofecoxib from the market. First, the current postmarketing surveillance system does not work. If the FDA is to continue to approve drugs rapidly, we should not expect that all safety issues will be understood prior to a drug's approval." The editorial authors add that an improved system of postmarketing surveillance is needed.

"Fortunately, many patients taking coxibs can be switched to other equally effective and evidence-based analgesic (pain relieving) regimens."

"The market withdrawal of rofecoxib has brought to the forefront concerns about the drug safety system that have been raised before. These issues must be addressed now if we are to restore the public's confidence in the safety of our pharmacologic armamentarium and provide physicians and patients with the data we all need to prescribe drugs safely."