PMID- 19223284
OWN - NLM
STAT- MEDLINE
DCOM- 20090515
LR  - 20211028
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 48
IP  - 4
DP  - 2009 Apr
TI  - Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs 
      diclofenac in a randomized controlled clinical trial (The MEDAL study).
PG  - 425-32
LID - 10.1093/rheumatology/kep005 [doi]
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 
      3.4-3.6 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.
FAU - Combe, Bernard
AU  - Combe B
AD  - Service d'Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France. 
      b-combe@chu-montpellier.fr
FAU - Swergold, Gary
AU  - Swergold G
FAU - McLay, James
AU  - McLay J
FAU - McCarthy, Timothy
AU  - McCarthy T
FAU - Zerbini, Cristiano
AU  - Zerbini C
FAU - Emery, Paul
AU  - Emery P
FAU - Connors, Laurine
AU  - Connors L
FAU - Kaur, Amarjot
AU  - Kaur A
FAU - Curtis, Sean
AU  - Curtis S
FAU - Laine, Loren
AU  - Laine L
FAU - Cannon, Christopher P
AU  - Cannon CP
LA  - eng
GR  - 18475/ARC_/Arthritis Research UK/United Kingdom
GR  - 18475/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090217
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Sulfones)
RN  - 144O8QL0L1 (Diclofenac)
RN  - WRX4NFY03R (Etoricoxib)
SB  - IM
MH  - Aged
MH  - Cardiovascular Diseases/chemically induced
MH  - Cyclooxygenase Inhibitors/*adverse effects/therapeutic use
MH  - Diclofenac/*adverse effects/therapeutic use
MH  - Double-Blind Method
MH  - Emergencies
MH  - Etoricoxib
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Odds Ratio
MH  - Osteoarthritis/complications/*drug therapy
MH  - Pyridines/*adverse effects/therapeutic use
MH  - Safety
MH  - Sample Size
MH  - Sulfones/*adverse effects/therapeutic use
MH  - Thrombosis/*chemically induced
EDAT- 2009/02/19 09:00
MHDA- 2009/05/16 09:00
CRDT- 2009/02/19 09:00
PHST- 2009/02/19 09:00 [entrez]
PHST- 2009/02/19 09:00 [pubmed]
PHST- 2009/05/16 09:00 [medline]
AID - kep005 [pii]
AID - 10.1093/rheumatology/kep005 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2009 Apr;48(4):425-32. doi: 10.1093/rheumatology/kep005. 
      Epub 2009 Feb 17.