39219
document
Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial ( The MEDAL study ) . 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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Intervention_Pharmacological
etoricoxib
39221
Intervention_Pharmacological
diclofenac
39222
Intervention_Pharmacological
etoricoxib
39223
Intervention_Pharmacological
diclofenac
39224
Intervention_Pharmacological
etoricoxib
39225
Intervention_Pharmacological
diclofenac
39226
Intervention_Pharmacological
etoricoxib
39227
Intervention_Pharmacological
diclofenac
39228
Intervention_Pharmacological
etoricoxib
39229
Intervention_Pharmacological
etoricoxib
39230
Intervention_Pharmacological
etoricoxib
39231
Intervention_Pharmacological
diclofenac
39232
Intervention_Pharmacological
etoricoxib
39233
Intervention_Pharmacological
diclofenac
39234
Intervention_Pharmacological
etoricoxib
39235
Intervention_Pharmacological
etoricoxib
39236
Intervention_Pharmacological
diclofenac
39237
Intervention_Pharmacological
diclofenac
39238
Intervention_Pharmacological
etoricoxib
39239
Outcome_Other
Cardiovascular safety
39240
Outcome_Other
gastrointestinal tolerability
39241
Outcome_Other
cardiovascular ( CV ) and other safety and efficacy parameters
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Outcome_Other
Other safety and efficacy parameters
39243
Outcome_Other
thrombotic CV risk hazard ratio
39244
Outcome_Adverse-effects
cumulative gastrointestinal ( GI ) /liver adverse events ( AEs ) discontinuation rate
39245
Outcome_Physical
systolic blood pressure
39246
Outcome_Other
efficacy
39247
Outcome_Physical
thrombotic CV events
39248
Outcome_Physical
renovascular AEs
39249
Outcome_Other
GI/liver tolerability profile
39250
Participant_Condition
OA patients
39251
Participant_Condition
RA patients
39252
Participant_Sample-size
23 504