A big study published in 2016, called the PRECISION trial, found that people with arthritis who take the anti-inflammatory drug ibuprofen are more likely to develop cardiovascular problems than those using celecoxib – and now researchers think they know why. Ibuprofen raises blood pressure, according to new findings presented recently at the annual meeting of the European Society of Cardiology in Barcelona.
These findings were based on the results of a sub-study of the PRECISION trial, called PRECISION-ABPM. Both studies looked at patients at risk of heart disease who took one of three common pain relievers for arthritis: celecoxib (Celebrex), ibuprofen (such as Motrin) or naproxen (such as Aleve). All three of the medications belong to a class called nonsteroidal anti-inflammatory drugs (NSAIDs); buprofen and naproxen are so-called nonselective NSAIDs, whereas celecoxib is a selective COX-2 inhibitor.
These drugs are among the most commonly prescribed worldwide; in the United States, about 30 million people with osteoarthritis (OA) take them, 40 percent of whom already have high blood pressure.
It’s well established that all NSAIDs, including about a dozen not analyzed in the PRECISION studies, increase the risk of heart attack and stroke, especially in people over 65 with a history of heart disease. In 2015, the Food and Drug Administration (FDA) warned that the risks of NSAIDs were greater than originally thought and required manufacturers to put a warning on the label. But it wasn’t clear if some NSAIDs were riskier than others.
PRECISION was a decade-long study that attempted to answer that question. It was mandated by the FDA (and funded by Pfizer, the maker of Celebrex) after rofecoxib (Vioxx), a COX-2 inhibitor like celecoxib, was pulled from the market for safety reasons. (A third COX-2 inhibitor, valdecoxib (Bextra) was pulled off the market shortly after rofecoxib.) PRECISION was intended to determine if celecoxib had the same high risk of heart attack and stroke as the others.
But the trial found the opposite of what was expected: Celecoxib turned out to be safer than either ibuprofen or naproxen.
PRECISION-ABPM looked at the specific effect of the three drugs on blood pressure. It lasted four months and involved 444 arthritis patients, most with OA. It showed ibuprofen raised blood pressure by almost 4 mmHg (millimeters of mercury, the common measure for blood pressure) over 24 hours compared to a 1.6 point increase with naproxen and a slight decrease (0.3 mmHg) with celecoxib.
“Since decreasing systolic blood pressure by just 2 mmHg lowers stroke mortality by 10 percent and ischaemic heart disease mortality by 7 percent, increases in systolic blood pressure associated with NSAIDs as observed in PRECISION-ABPM should be considered clinically relevant,” says principal investigator Frank Ruschitzka, professor of cardiology and co-head of the department of cardiology at the University Heart Centre in Zurich, Switzerland, in a press statement.
Even patients who had normal blood pressure to begin with ended up with hypertension – 23 percent of those taking ibuprofen, 19 percent with naproxen and 10 percent with celecoxib.
“Patients receiving ibuprofen had a 61 percent higher incidence of de novo hypertension compared to those receiving celecoxib,” Ruschitzka noted.
NSAIDs Still a Threat
Do the study results mean it’s safe to take celecoxib for arthritis? Not necessarily. Although the patients in the PRECISION studies took daily doses of NSAIDs, some doctors think the drugs should only be used short-term, on an as-needed basis or not at all.
Peter Wilson, MD, a professor of medicine and public health at Emory University who served on the FDA’s expert panel on NSAIDs, says the drugs may be useful for short-term relief for younger people with no history of heart disease.
According to Vladimir Kramskiy, MD, a neurologist and director of the Ambulatory Recuperative Pain Medicine Program at Hospital for Special Surgery in New York City, “NSAIDs should only be used when they are needed most – for example, first thing in the morning or after exercise – to avoid serious gastrointestinal, cardiac and renal side effects.”
Other doctors argue that there are better options. Many, like Geoffrey Westrich, MD, research director of Adult Reconstruction and Joint Replacement Service, also at Hospital for Special Surgery in New York City, think exercise and maintaining a healthy weight are among the best treatments for arthritis pain.
Author: Linda Rath
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