Literature DB >> 19223284

Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study).

Bernard Combe1, Gary Swergold, James McLay, Timothy McCarthy, Cristiano Zerbini, Paul Emery, Laurine Connors, Amarjot Kaur, Sean Curtis, Loren Laine, Christopher P Cannon.   

Abstract

OBJECTIVE: To compare cardiovascular (CV) and other safety and efficacy parameters of etoricoxib 60 and 90 mg, and diclofenac 150 mg.
METHODS: This double-blind study randomized OA patients to etoricoxib 90 mg, then to 60 mg once daily vs diclofenac 75 mg twice daily; RA patients were randomized to etoricoxib 90 mg once daily or diclofenac 75 mg twice daily. The primary endpoint was non-inferiority of etoricoxib vs diclofenac for thrombotic CV events (95% CI upper bound of hazard ratio <1.30). Other safety and efficacy parameters were evaluated in cohorts of patients based on etoricoxib dose and disease.
RESULTS: A total of 23 504 patients were randomized with mean treatment duration from 19.4 to 20.8 months. The thrombotic CV risk hazard ratio (HR) (etoricoxib to diclofenac) was 0.96 (95% CI 0.81, 1.15), consistent with non-inferiority of etoricoxib to diclofenac. The cumulative gastrointestinal (GI)/liver adverse events (AEs) discontinuation rate was significantly lower for etoricoxib than diclofenac in each patient cohort; HR (95% CI) of 0.46 (0.39, 0.54), 0.52 (0.42, 0.63) and 0.49 (0.39, 0.62) for the 60 mg OA, 90 mg OA and RA cohorts. The maximum average change in systolic blood pressure (BP) with etoricoxib was 3.4-3.6 mmHg (diastolic BP: 1.0-1.5 mmHg), while diclofenac produced a maximum average change of 0.9-1.9 mmHg (diastolic BP: 0.0-0.5 mmHg). Both agents resulted in similar efficacy regardless of etoricoxib dose.
CONCLUSION: Long-term etoricoxib use is associated with a risk of thrombotic CV events comparable with that of diclofenac. Compared with diclofenac, etoricoxib demonstrated a greater risk of renovascular AEs, but a more favourable GI/liver tolerability profile.

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Year:  2009        PMID: 19223284     DOI: 10.1093/rheumatology/kep005

Source DB:  PubMed          Journal:  Rheumatology (Oxford)        ISSN: 1462-0324            Impact factor:   7.580


  16 in total

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Journal:  Ther Adv Musculoskelet Dis       Date:  2014-08       Impact factor: 5.346

2.  Nonsteroidal Anti-Inflammatory Drugs and Risk of First Hospitalization for Heart Failure in Patients with No History of Heart Failure: A Population-Based Case-Crossover Study.

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Review 3.  Coronary Risks Associated with Diclofenac and Other NSAIDs: An Update.

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Journal:  Drug Saf       Date:  2020-04       Impact factor: 5.606

4.  Increased incidence and impact of upper and lower gastrointestinal events in patients with rheumatoid arthritis in Olmsted County, Minnesota: a longitudinal population-based study.

Authors:  Elena Myasoedova; Eric L Matteson; Nicholas J Talley; Cynthia S Crowson
Journal:  J Rheumatol       Date:  2012-04-01       Impact factor: 4.666

Review 5.  Etoricoxib: a review of its use in the symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis.

Authors:  Katherine F Croom; M Asif A Siddiqui
Journal:  Drugs       Date:  2009-07-30       Impact factor: 9.546

6.  Musculoskeletal pain: prescription of NSAID and weak opioid by primary health care physicians in Sweden 2004-2008 - a retrospective patient record review.

Authors:  Metha Brattwall; Ibrahim Turan; Jan Jakobsson
Journal:  J Pain Res       Date:  2010-08-04       Impact factor: 3.133

7.  Efficacy and Safety of COX-2 Inhibitors in the Clinical Management of Arthritis: Mini Review.

Authors:  Sam T Mathew; Gayathri Devi S; V V Prasanth; B Vinod
Journal:  ISRN Pharmacol       Date:  2011-05-17

Review 8.  Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: a network meta-analysis.

Authors:  Anneloes van Walsem; Shaloo Pandhi; Richard M Nixon; Patricia Guyot; Andreas Karabis; R Andrew Moore
Journal:  Arthritis Res Ther       Date:  2015-03-19       Impact factor: 5.156

Review 9.  NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species.

Authors:  Rajeshwary Ghosh; Azra Alajbegovic; Aldrin V Gomes
Journal:  Oxid Med Cell Longev       Date:  2015-09-20       Impact factor: 6.543

10.  Future directions for the management of pain in osteoarthritis.

Authors:  Nidhi Sofat; Anasuya Kuttapitiya
Journal:  Int J Clin Rheumtol       Date:  2014-04
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