Arthritis drugs known as COX-2 inhibitors raise blood pressure more than older pain relievers, which may explain why the newer medicines have been linked to heart attacks, Australian researchers reported on Monday.
The increases were small and varied among the different COX-2 drugs. The risk seemed highest with Merck & Co. Inc.’s Vioxx, the researchers said after reviewing data from more than 45,000 people in 19 studies. Merck pulled Vioxx from the market last September. The study was published online on Monday by the Archives of Internal Medicine. The safety of pain relievers is under scrutiny from regulators. A U.S. advisory committee will review the medicines at a three-day meeting starting on Wednesday. The Archives of Internal Medicine said it released the findings early because they were relevant to the meeting. One of the authors of the new study, Henry Krum, said the blood pressure increases seen with the COX-2 drugs were small, but they may be enough to help spur heart attacks. “One could draw the conclusion the elevations in blood pressure are contributing to the increase in cardiovascular risk,” said Krum, director of the National Health and Medical Research Council of Australia’s Center of Clinical Research Excellence in Therapeutics. Some COX-2 inhibitors, as well as older pain relievers called nonsteroidal anti-inflammatory drugs or NSAIDs, had already been linked to higher blood pressure. The new study was designed to determine if the widely used COX-2 drugs raised blood pressure more than NSAIDs such as ibuprofen and naproxen. The COX-2 drugs studied were Merck’s Vioxx and Arcoxia and Pfizer Inc.’s Celebrex. On average, systolic blood pressure — the upper number of a blood pressure measurement — was 2.83 millimeters of mercury higher with COX-2 inhibitors than with NSAIDs. Diastolic pressure — the lower number — was 1.34 millimeters of mercury higher with the COX-2 drugs. Vioxx “clearly is the most dramatic in elevating blood pressure,” while Celebrex “looks pretty clean,” Krum said.The data on Arcoxia, which is approved in some countries but not the United States, were too limited to draw conclusions, Krum said. Merck spokeswoman Casey Stavropoulos noted the study was an analysis of previously published research. “There will be a more complete review of selective COX-2 inhibitors and blood pressure at the (Food and Drug Administration) committee meeting later this week,” she said. COX-2 inhibitors were developed with the hope they would reduce pain as much as NSAIDs while being gentler on the stomach. NSAIDs can cause potentially fatal stomach and intestinal bleeding. Only Vioxx has been shown to produce fewer serious gastric problems than NSAIDs. Vioxx was pulled after a study showed the drug doubled heart attack and stroke risk in patients who took it for at least 18 months. “Clinicians need to weigh the risks of improved gastrointestinal safety versus potential hazards of developing elevated blood pressure when considering the use of these agents, especially in the elderly population,” Krum and his colleagues wrote. The research was funded by grants from Australia’s National Health and Medical Research Council and the Royal Australasian College of Physicians. Krum has received consulting fees from Pfizer, Merck and Novartis — all makers of COX-2 inhibitors. Another of the study’s authors was a consultant to Pfizer.(Source: Archives of Internal Medicine: Reuters Health: Lisa Richwine: February 2005.)