RESEARCH - Cardiovascular outcomes with etoricoxib and diclofenac in patients with OA and RA - MEDAL

[Guest guest]

Lancet. 2006 Nov 18;368(9549):1771-81.

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.

Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin

AS, Bombardier C, Weinblatt ME, van der Heijde D, Erdmann E, Laine L; MEDAL

Steering Committee.

Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular

Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

02115, USA. cpcannon@...

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-inflammatory 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 prespecified 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, defined 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 1.24 and 1.30 per 100 patient-years and a hazard

ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac.

Rates of upper gastrointestinal clinical events (perforation, bleeding,

obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs

0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of

complicated upper gastrointestinal events were similar for etoricoxib (0.30)

and diclofenac (0.32).

INTERPRETATION: Rates of thrombotic cardiovascular events in patients with

arthritis on etoricoxib are similar to those in patients on diclofenac with

long-term use of these drugs.

PMID: 17113426

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

7113426

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org