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

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

Research output: Contribution to journalArticle

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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 3.43.6 mmHg (diastolic BP: 1.01.5 mmHg), while diclofenac produced a maximum average change of 0.91.9 mmHg (diastolic BP: 0.00.5 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.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalRheumatology
Volume48
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • NSAIDs
  • rheumatoid arthritis
  • osteoarthritis
  • COX-2 inhibitors
  • cardiovascular safety
  • gastrointestinal safety
  • analgesia
  • nonsteroidal antiinflammatory drugs
  • rheumatoid-arthritis
  • inhibitor etoricoxib
  • multinational etoricoxib
  • metaanalysis
  • rofecoxib
  • naproxen
  • events
  • COX-2

Cite this

Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study). / Combe, Bernard; Swergold, Gary; McLay, James; McCarthy, Timothy; Zerbini, Cristiano; Emery, Paul; Connors, Laurine; Kaur, Amarjot; Curtis, Sean; Laine, Loren; Cannon, Christopher P.

In: Rheumatology, Vol. 48, No. 4, 04.2009, p. 425-432.

Research output: Contribution to journalArticle

Combe, B, Swergold, G, McLay, J, McCarthy, T, Zerbini, C, Emery, P, Connors, L, Kaur, A, Curtis, S, Laine, L & Cannon, CP 2009, 'Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study)', Rheumatology, vol. 48, no. 4, pp. 425-432. https://doi.org/10.1093/rheumatology/kep005
Combe, Bernard ; Swergold, Gary ; McLay, James ; McCarthy, Timothy ; Zerbini, Cristiano ; Emery, Paul ; Connors, Laurine ; Kaur, Amarjot ; Curtis, Sean ; Laine, Loren ; Cannon, Christopher P. / Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study). In: Rheumatology. 2009 ; Vol. 48, No. 4. pp. 425-432.
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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 3.43.6 mmHg (diastolic BP: 1.01.5 mmHg), while diclofenac produced a maximum average change of 0.91.9 mmHg (diastolic BP: 0.00.5 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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AU - Combe, Bernard

AU - Swergold, Gary

AU - McLay, James

AU - McCarthy, Timothy

AU - Zerbini, Cristiano

AU - Emery, Paul

AU - Connors, Laurine

AU - Kaur, Amarjot

AU - Curtis, Sean

AU - Laine, Loren

AU - Cannon, Christopher P.

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N2 - 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 3.43.6 mmHg (diastolic BP: 1.01.5 mmHg), while diclofenac produced a maximum average change of 0.91.9 mmHg (diastolic BP: 0.00.5 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.

AB - 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 3.43.6 mmHg (diastolic BP: 1.01.5 mmHg), while diclofenac produced a maximum average change of 0.91.9 mmHg (diastolic BP: 0.00.5 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.

KW - NSAIDs

KW - rheumatoid arthritis

KW - osteoarthritis

KW - COX-2 inhibitors

KW - cardiovascular safety

KW - gastrointestinal safety

KW - analgesia

KW - nonsteroidal antiinflammatory drugs

KW - rheumatoid-arthritis

KW - inhibitor etoricoxib

KW - multinational etoricoxib

KW - metaanalysis

KW - rofecoxib

KW - naproxen

KW - events

KW - COX-2

U2 - 10.1093/rheumatology/kep005

DO - 10.1093/rheumatology/kep005

M3 - Article

VL - 48

SP - 425

EP - 432

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

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