Ibuprofen (brand names Advil or Motrin) is known to be linked to increased blood pressure and hypertension when compared to celecoxib (brand names Celebrex) in patients with osteoarthritis or rheumatoid arthritis and a heightened risk of cardiovascular disease, according to the latest results from the PRECISION-ABM (Ambulatory Blood Pressure Measurement) study presented on August 28 in a Hot Line Session at the European Society of Cardiology (ESC) Congress and published in the European Heart Journal (EHJ).
With the exception of aspirin, almost all nonsteroidal anti-inflammatory drugs, including those available over-the-counter, have adverse consequences on the cardiovascular system. PRECISION’s purpose was to compare the cardiovascular safety for the chronic use of three NSAIDs used to treat arthritis.
Nonsteroidal anti-inflammatory drugs (NSAIDs), both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most popular and widely prescribed drugs globally, but are associated with increased blood pressure and adverse cardiovascular events. Approximately 19 percent of the United States population use at least one NSAID on a regular basis, including 30 million American with osteoarthritis, 40 percent of whom also have hypertension.
Warning Labels on NSAID Drugs
NSAID labels have warnings about potential increases in blood pressure but there is minimal data on the effects of individual drugs. Achieving or maintaining blood pressure control in patients with arthritis and accompanying hypertension (treated or untreated) could avoid 60,000 deaths from coronary heart disease and over 70,000 deaths from stroke each year, making it a priority to examine the effects of various NSAIDs on blood pressure.
Studies of Blood Pressure Effects
PRECISION-ABPM is a pre-specified four-month sub-study of the landmark PRECISION trial,4 was designed to determine the blood pressure effects of the selective COX-2 inhibitor celecoxib compared to the non-selective NSAIDs naproxen (Aleve) and ibuprofen.
PRECISION-ABPM was a double-blind, prospective, randomized non-inferiority cardiovascular safety trial. The study was performed at 60 sites in the U.S. and included 444 patients, of whom 408 (92 percent) had osteoarthritis and 36 (8 percent) had rheumatoid arthritis. All patients were at increased risk, or had evidence of coronary artery disease.
Participants were randomized in a 1:1:1 fashion to receive celecoxib (100-200 mg twice a day), ibuprofen (600-800 mg three times a day), or naproxen (375-500 mg twice a day) with matching placebos. The primary endpoint was the change from baseline in 24-hour ambulatory blood pressure after four months.
Principal investigator Professor Frank Ruschitzka, professor of cardiology and co-head, Department of Cardiology, University Heart Centre, Zurich, Switzerland, said, “PRECISION-ABPM showed differential blood pressure effects between the different NSAIDs, ibuprofen, and naproxen, and the COX-2 inhibitor celecoxib. While celecoxib and naproxen produced either a slight decrease (celecoxib) or a relatively small increase (naproxen) in blood pressure, ibuprofen was associated with a significant increase in ambulatory systolic blood pressure of more than 3 mmHg.”
How Celecoxib Works
Celecoxib works by blocking the enzyme in the body that makes prostaglandins. COX-2 enzymes are responsible for releasing prostaglandins after infection or injury. Decreasing prostaglandins helps to reduce pain and swelling.
By specifically only blocking COX-2 enzymes, COX-2 inhibitors relieve inflammation and pain with less adverse gastrointestinal effects than NSAIDs that inhibit both COX-1 and COX-2 enzymes. However, they are not entirely devoid of gastrointestinal effects, and their use, like all NSAIDs, has been associated with a higher risk of heart attack and stroke, according to Drugs.com.
Additional Comparison Study
An additional analysis showed that the percentage of patients with normal baseline blood pressure who developed hypertension was 23.2 percent for ibuprofen, 19.0 percent for naproxen, and 10.3 percent for celecoxib odds ratio [OR] 0.39, p=0.004 and OR 0.49, p=0.03 for celecoxib versus ibuprofen and naproxen, respectively.
“Patients receiving ibuprofen had a 61 percent higher incidence of de novo hypertension compared to those receiving celecoxib,” said Professor Ruschitzka. These results support and extend the findings of the PRECISION trial, showing noninferiority for the primary cardiovascular outcomes for moderate doses of celecoxib compared with naproxen or ibuprofen. These findings may have the greatest clinical significance in the elderly, who have a high incidence of arthritis and hypertension.
Professor Ruschitzka said: “The current findings suggest that the elevated cardiovascular risk with NSAIDs may be partly due to drug-specific increases in blood pressure. This challenges the widely held belief that conventional NSAIDs, like naproxen and ibuprofen, with their higher COX-1 (and thromboxane reducing) effects would provide greater cardiovascular safety than other more COX-2 selective agents, especially celecoxib.”
Professor Ruschitzka concluded: “PRECISION-ABPM clearly demonstrates that NSAIDs, particularly ibuprofen, may be not as safe as previously thought. Patients should continue to consult their doctor before taking NSAIDs or coxibs and clinicians need to weight the potential hazards of worsening blood pressure control when considering the use of these agents.”