Ibuprofen Elevates Blood Pressure in Arthritis

August 28, 2017

Hypertension goes up more than with celecoxib in patients who are at increased risk for cardiovascular disease.

Ibuprofen increases blood pressure and hypertension more than celecoxib in patients who have osteoarthritis or rheumatoid arthritis and are at increased risk for cardiovascular disease, according to study results presented at the European Society of Cardiology’s ESC Congress 2017 in Barcelona.

Although NSAIDs (nonselective and selective cyclooxygenase-2 [COX-2] inhibitors) are among the most widely prescribed drugs worldwide, they are linked with increased blood pressure and adverse cardiovascular events, researchers noted.

The investigators conducted the PRECISION-ABPM study, a prespecified 4-month substudy of the landmark PRECISION trial, to determine the blood pressure effects of the selective COX-2 inhibitor celecoxib compared with the nonselective NSAIDs naproxen and ibuprofen.

PRECISION-ABPM, a prospective, double-blind, randomized, noninferiority cardiovascular safety trial, involved 60 sites in the United States. Of 444 patients, 408 (92%) had osteoarthritis and 36 (8%) had rheumatoid arthritis. All had evidence of, or were at increased risk for, coronary artery disease.

The researchers randomized patients in a 1:1:1 fashion to receive celecoxib (100 to 200 mg twice a day), ibuprofen (600 to 800 mg 3 times a day), or naproxen (375 to 500 mg twice a day) with matching placebos. The change from baseline in 24-hour ambulatory blood pressure after 4 months was the primary end point.

Celecoxib decreased the average systolic blood pressure measured over 24 hours by -0.3 mmHg; ibuprofen and naproxen increased it by 3.7 mmHg and 1.6 mmHg, respectively. The resulting difference of -3.9 mmHg between celecoxib and ibuprofen was significant.

“PRECISION-ABPM showed differential blood pressure effects between the different NSAIDs, ibuprofen and naproxen, and the COX-2 inhibitor celecoxib,” said principal investigator Frank Ruschitzka, professor of cardiology and co-head, Department of Cardiology, University Heart Centre, Zurich, Switzerland.

“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.”

In an additional analysis, the percentage of patients with normal baseline blood pressure in whom hypertension developed was 23.2% for ibuprofen, 19.0% for naproxen, and 10.3% for celecoxib.

“Patients receiving ibuprofen had a 61% 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, demonstrating noninferiority for the primary cardiovascular outcomes for moderate doses of celecoxib compared with naproxen or ibuprofen, the researchers noted, adding that the findings may have the greatest clinical significance in older patients, in whom the prevalence of arthritis and hypertension is high.

“The current findings suggest that the elevated cardiovascular risk with NSAIDs may be partly due to drug-specific increases in blood pressure,” Professor Ruschitzka said. “This challenges the widely cited hypothesis that the adverse effects of NSAIDs relate directly to their effects on platelets and endothelial cells.”

“PRECISION-ABPM clearly demonstrates that NSAIDs, particularly ibuprofen, may be not as safe as previously thought,” Professor Ruschitzka concluded. “Patients with osteoarthritis and arthritis should continue to consult their doctor before taking NSAIDs or coxibs and clinicians need to weigh the potential hazards of worsening blood pressure control when considering the use of these agents.”

“Since decreasing systolic blood pressure by just 2 mmHg lowers stroke mortality by 10% and ischaemic heart disease mortality by 7%, increases in systolic blood pressure associated with NSAIDs as observed in PRECISION-ABPM should be considered clinically relevant.”

Disclosures:

The study was funded by Pfizer. All authors involved in the study did not accept honoraria, consulting fees, or any other compensation related to NSAIDs during the entire course of the study.