Drug-specific effects of NSAIDs on BP may impact CV risk
Late-breaking data presented at the European Society of Cardiology Congress 2017 in Barcelona, Spain have shown that ibuprofen is associated with greater increase in blood pressure (BP) than celecoxib or naproxen in patients with arthritis, potentially increasing their risk of cardiovascular (CV) events. [Eur Heart J 2017, doi: 10.1093/eurheartj/ehx508]
“Both selective and nonselective NSAIDs are amongst the most widely prescribed drugs worldwide, but are linked with increased BP and CV events,” said lead investigator Dr Frank Ruschitzka from the University Heart Centre in Zurich, Switzerland. “PRECISION-ABPM [Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen Or Naproxen - Ambulatory Blood Pressure Measurement] was designed to determine the effects of the selective COX-2 inhibitor celecoxib on BP, as compared with the nonselective NSAIDs naproxen and ibuprofen.”
In the randomized, multicentre trial, 444 patients with osteoarthritis or rheumatoid arthritis who had evidence of or were at increased risk of coronary artery disease received celecoxib (100–200 mg BID), ibuprofen (600–800 mg TID) or naproxen (375–500 mg BID) with matching placebos in a 1:1:1 allocation. The primary endpoint was change from baseline in 24-hour ambulatory BP at 4 months. Baseline patient characteristics in terms of age, gender, BP, laboratory tests and co-medication were well matched between the groups.
The change in mean 24-hour systolic BP at 4 months was -0.3 mm Hg for celecoxib, +3.7 mm Hg for ibuprofen and +1.6 mm Hg for naproxen, and these differences manifested regardless of comorbidities such as baseline hypertension or chronic kidney disease. Similar differences between the drugs were observed for diastolic and arterial BP.
“The changes in systolic BP resulted in a significant difference of -3.9 mm Hg between celecoxib and ibuprofen [p=0.0009]. The -1.8 mm Hg difference between celecoxib and naproxen and -2.1 mm Hg difference between naproxen and ibuprofen were not statistically significant,” noted Ruschitzka.
In addition, patients receiving ibuprofen had a 61 percent higher incidence of new-onset hypertension. “The percentage of patients with normal baseline BP who developed hypertension at 4 months was 10.3 percent for celecoxib, 23.2 percent for ibuprofen and 19.0 percent for naproxen,” he reported.
These results support and extend the findings of the original PRECISION trial, which showed a 40 percent lower rate of hospitalization for hypertension with celecoxib vs ibuprofen (p=0.04) but not significantly lower with celecoxib vs naproxen. [N Engl J Med 2016;375:2519-2529]
“The PRECISION trial, which included over 24,000 patients, also indicated a trend towards lower CV and all-cause mortality with celecoxib as compared with ibuprofen or naproxen,” said Ruschitzka.
The finding that ibuprofen is associated with a significant increase in BP, a higher incidence of new-onset hypertension and a higher CV risk suggests that the elevated CV risk with NSAIDs may be partly due to drug-specific increases in BP.
“Increases in systolic BP with different NSAIDs as observed in PRECISION-ABPM should be considered clinically significant, especially for the elderly population with a high prevalence of arthritis and hypertension,” he concluded.