www.thelancet.com Vol 368 November 18, 2006
Cardiovascular outcomes with etoricoxib and diclofenac in
patients with osteoarthritis and rheumatoid arthritis in the
Multinational Etoricoxib and Diclofenac Arthritis Long-term
(MEDAL) programme: a randomised comparison
Christopher P Cannon, Sean P Curtis, Garret A FitzGerald, Henry Krum, Amarjot Kaur, James A Bolognese, Alise S Reicin, Claire Bombardier,
Michael E Weinblatt, Désirée van der Heijde, Erland Erdmann, Loren Laine, for the MEDAL Steering Committee*
Background Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic
cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of
assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-infl ammatory drugs
(NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events
with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac.
Methods We designed a prespecifi ed pooled analysis of data from three trials in which patients with osteoarthritis or
rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The
primary hypothesis stated that etoricoxib is not inferior to diclofenac, defi ned as an upper boundary of less than
1·30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis.
Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www.
clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445.
Findings 34 701 patients (24 913 with osteoarthritis and 9 787 with rheumatoid arthritis) were enrolled. Average
treatment duration was 18 months (SD 11·8). 320 patients in the etoricoxib group and 323 in the diclofenac group had
thrombotic cardiovascular events, yielding event rates of 1·2