The VIOXX in Prostate Cancer Prevention study: cardiovascular events observed in the rofecoxib 25 mg and placebo treatment groups.
BACKGROUND
A double-blind, randomized, placebo-controlled study was designed to determine the cumulative incidence of developing prostate cancer over 6 years of treatment with rofecoxib 25 mg/day versus placebo. Before completion, this trial was terminated following the voluntary withdrawal of rofecoxib. (On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.) Here we report the cardiovascular (CV) safety data collected from this study.


METHODS
A total of 4741 men (44-81 years old) exhibiting prostate-specific antigen levels (PSA) between 2.5 and 10 ng/mL were enrolled. Patients were stratified by PSA level and use of low-dose aspirin (LDA), then randomized to rofecoxib 25 mg (n = 2369) or placebo (n = 2372). Safety data were analyzed in all patients receiving > or = 1 dose of study medication. All reported thrombotic CV events occurring on-treatment or within 14 days after study drug discontinuation were adjudicated by an independent panel of clinical experts blinded to treatment assignment. Rates per 100 patient-years and relative risk (RR) of thrombotic CV events, rofecoxib vs. placebo, were determined.


RESULTS
Approximately 36% of patients had > or = 2 CV risk factors or LDA indicated. Median treatment duration was 4.14 (range: 0.03-15.90) months. Twenty-nine patients (14 rofecoxib, rate 1.27; 15 placebo, rate 1.36) experienced confirmed thrombotic CV events; RR 0.94 (95% CI: 0.45, 1.94) vs. placebo. Four patients (one rofecoxib; three placebo) died due to a confirmed thrombotic event. Significantly (p = 0.002) more patients receiving rofecoxib (n = 20; 0.8%) experienced hypertension-related adverse events versus placebo (n = 2; 0.1%). There were no cases of congestive heart failure.


CONCLUSIONS
Rofecoxib 25 mg and placebo demonstrated similar risk of thrombotic CV events in this limited dataset.
van Adelsberg
Janet
J
Merck Research Laboratories, Rahway, NJ 07065, USA. janet_vanadelsberg@merck.com
Gann
Peter
P
Ko
Amy T
AT
Damber
Jan-Erik
JE
Logothetis
Christopher
C
Marberger
Michael
M
Schmitz-Drager
Bernd J
BJ
Tubaro
Andrea
A
Harms
Celia J
CJ
Roehrborn
Claus
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D010919:Placebos; D013450:Sulfones; C116926:rofecoxib; D017430:Prostate-Specific Antigen