title: Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study).
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service d'Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France. b-combe@chu-montpellier.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
authors.forename: Gary
authors.initials: G
authors.lastname: Swergold
authors.forename: James
authors.initials: J
authors.lastname: McLay
authors.forename: Timothy
authors.initials: T
authors.lastname: McCarthy
authors.forename: Cristiano
authors.initials: C
authors.lastname: Zerbini
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Laurine
authors.initials: L
authors.lastname: Connors
authors.forename: Amarjot
authors.initials: A
authors.lastname: Kaur
authors.forename: Sean
authors.initials: S
authors.lastname: Curtis
authors.forename: Loren
authors.initials: L
authors.lastname: Laine
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004008:Diclofenac / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004630:Emergencies; D000077613:Etoricoxib; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D012449:Safety; D018401:Sample Size; D013450:Sulfones / Q000009:adverse effects* / Q000627:therapeutic use; D013927:Thrombosis / Q000139:chemically induced*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D004008:Diclofenac; D000077613:Etoricoxib