Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis.
BACKGROUND
Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain.


METHODS
The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) < or =1.33 and point estimate < or =1.12 for both intent-to-treat (ITT) and modified ITT populations.


CONCLUSIONS
PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.
Becker
Matthew C
MC
Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
Wang
Thomas H
TH
Wisniewski
Lisa
L
Wolski
Kathy
K
Libby
Peter
P
Lüscher
Thomas F
TF
Borer
Jeffrey S
JS
Mascette
Alice M
AM
Husni
M Elaine
ME
Solomon
Daniel H
DH
Graham
David Y
DY
Yeomans
Neville D
ND
Krum
Henry
H
Ruschitzka
Frank
F
Lincoff
A Michael
AM
Nissen
Steven E
SE