Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) Trial.

Abstract

AIMS:

Non-steroidal anti-inflammatory drugs (NSAIDs), both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely prescribed drugs worldwide, but associate with increased blood pressure (BP) and adverse cardiovascular (CV) events. PRECISION-ABPM, a substudy of PRECISION was conducted at 60 sites, to determine BP effects of the selective COX-2 inhibitor celecoxib vs. the non-selective NSAIDs naproxen and ibuprofen.

METHODS AND RESULTS:

In this double-blind, randomized, multicentre non-inferiority CV-safety trial, 444 patients (mean age 62 ± 10 years, 54% female) with osteoarthritis (92%) or rheumatoid arthritis (8%) and evidence of or at increased risk for 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, to assess the effect on 24-h ambulatory BP after 4 months. The change in mean 24-h systolic BP (SBP) in celecoxib, ibuprofen and naproxen-treated patients was -0.3 mmHg [95% confidence interval (CI), -2.25, 1.74], 3.7 (95% CI, 1.72, 5.58) and 1.6 mmHg (95% CI, -0.40, 3.57), respectively. These changes resulted in a difference of - 3.9 mmHg (P = 0.0009) between celecoxib and ibuprofen, of - 1.8 mmHg (P = 0.12) between celecoxib and naproxen, and of - 2.1 mmHg (P = 0.08) between naproxen and ibuprofen. The percentage of patients with normal baseline BP who developed hypertension (mean 24-h SBP ≥ 130 and/or diastolic BP ≥ 80 mmHg) was 23.2% for ibuprofen, 19.0% for naproxen, and 10.3% for celecoxib (odds ratio 0.39, P = 0.004 and odds ratio 0.49, P = 0.03 vs. ibuprofen and naproxen, respectively).

CONCLUSIONS:

In PRECISION-ABPM, allocation to the non-selective NSAID ibuprofen, compared with the COX-2 selective inhibitor celecoxib was associated with a significant increase of SBP, and a higher incidence of new-onset hypertension.

CLINICALTRIALS:

gov number NCT00346216.

• Authors: Frank Ruschitzka, Jeffrey S Borer, Henry Krum, Andreas J Flammer, Neville D Yeomans, Peter Libby, Thomas F Lüscher, Daniel H Solomon, M Elaine Husni, David Y Graham, Deborah A Davey, Lisa M Wisniewski, Venu Menon, Rana Fayyad, Bruce Beckerman, Dinu Iorga, A Michael Lincoff, Steven E Nissen
• Journal: European heart journal (Eur Heart J) Vol. 38 Issue 44 Pg. 3282-3292 (Nov 21 2017) ISSN: 1522-9645 [Electronic] England
• PMID: 29020251 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Naproxen
• Celecoxib
• Ibuprofen

Topics

• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects, pharmacology)
• Arthritis, Rheumatoid (drug therapy, physiopathology)
• Blood Pressure (drug effects)
• Celecoxib (administration & dosage, adverse effects, pharmacology)
• Coronary Artery Disease (etiology)
• Cyclooxygenase 2 Inhibitors (administration & dosage, adverse effects, pharmacology)
• Double-Blind Method
• Female
• Humans
• Hypertension (chemically induced)
• Ibuprofen (administration & dosage, adverse effects, pharmacology)
• Male
• Naproxen (administration & dosage, adverse effects, pharmacology)
• Osteoarthritis (drug therapy, physiopathology)
• Prospective Studies