Practice Update - ESC Congress 2017

Ibuprofen Is Associated with a Rise in Blood Pressure in Patients with Arthritis and Cardiovascular Risk – PRECISION-ABPM Trial

The results supported and extended the findings of the PRECISION trial, inasmuch as they demonstrated noninferiority of the primary cardiovascular outcomes with moderate doses of celecoxib vs naproxen or ibuprofen. The findings may hold the greatest clinical significance in the elderly, who suffer a high prevalence of arthritis and hypertension. “The findings suggested that the elevated cardiovascular risk with NSAIDs may be partly due to drug-specific increases in blood pressure, challenging the widely cited hypothesis that adverse effects of NSAIDs relate directly to their effects on platelets and endothelial cells," Dr. Ruschitzka said. He added, “Since decreasing systolic blood pressure by just 2 mmHg lowers stroke mortality by 10% and ischemic heart dis- ease mortality by 7%, increases in systolic blood pressure associated with NSAIDs as observed in PRECISION-ABPM should be considered clinically relevant.”

In patients with osteoarthritis or rheumatoid arthritis, ibuprofen was associated with increased blood pressure and hypertension compared with celecoxib as well as an increased risk of cardiovascular disease. This conclusion, based on results of the double-blind noninferiority cardiovascular safety trial called Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement (PRECISION- ABPM), was presented at the 2017 European Society of Cardiology (ESC) Congress, from August 26–30.

Dr. Frank Ruschitzka

F rank Ruschitzka, MD, of the University Heart Centre, Zurich, Switzerland, explained that nonsteroidal anti-inflammatory drugs (NSAIDs), both nonselective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely prescribed drugs worldwide, though they are linked with increased blood pressure and adverse cardiovascular events. One-fourth of the world’s population aged over 35 years has arthritis, and of these, almost half have or are at high risk of cardiovascular disease, particularly hyper- tension,” Dr. Ruschitzka said during his presentation. “Clinicians need to weigh the potential hazards of worsening blood pressure control and its clinical sequelae against the arthritis-mitigating benefits associated with the use of NSAIDs, par- ticularly ibuprofen. The landmark PRECISION study was a prospective, long-term noninferiority trial of 24,081 patients. It was designed to assess the cardiovascular safety of cel- ecoxib vs prescription-strength doses of ibuprofen and naproxen in patients with chronic pain from osteoarthritis or rheu- matoid arthritis. It was conducted at 60 sites in the US and included 444 patients, of whom 408 (92%) had osteoarthritis and 36 (8%) had rheu- matoid arthritis. All patients had evidence of, or were at increased risk for, coronary artery disease. PRECISION-ABPM, a prespecified 4-month substudy of the PRECISION trial, was designed to determine the blood pressure effects of the selective COX-2 inhibitor celecoxib compared to

the non-selective NSAIDs naproxen and ibuprofen. Patients were randomized 1:1:1 to celecoxib (100–200 mg twice a day), ibu- profen (600–800 mg three times a day), or naproxen (375–500 mg twice a day) or placebo. The primary endpoint was change from baseline in 24-h ambulatory blood pressure after 4 months. Celecoxib decreased average systolic blood pressure measured over 24 h by –0.3 mmHg. Ibuprofen and naproxen increased it by 3.7 and 1.6 mm Hg, respectively. The resulting difference of –3.9 mmHg between celecoxib and ibu- profen was significant (P = .009). According to Dr. Ruschitzka the PRECISION-ABPM showed differential blood pressure effects between the dif- ferent NSAIDs, ibuprofen and naproxen, and the COX-2 inhibitor celecoxib. While celecoxib and naproxen produced either a slight decrease (celecoxib) or a rela- tively small increase (naproxen) in blood pressure, ibuprofen was associated with a significant increase in ambulatory systolic blood pressure of more than 3 mmHg. An additional analysis showed that the percentage of patients with normal baseline blood pressure who developed hypertension (n=5) was 23.2% for ibu- profen, 19.0% for naproxen, and 10.3% for celecoxib (odds ratio 0.39, P = .004; and 0.49, P = .03 for celecoxib vs ibuprofen and naproxen, respectively). “Patients receiving ibuprofen experienced a 61% higher incidence of de novo hyper- tension vs those receiving celecoxib,” Dr. Ruschitzka said.

PracticeUpdate Editorial Team

PRACTICEUPDATE CONFERENCE SERIES • ESC Congress 2017 6