TY - JOUR
T1 - Cardiovascular events associated with rofecoxib
T2 - final analysis of the APPROVe trial
AU - Baron, John A.
AU - Sandler, Robert S.
AU - Bresalier, Robert S.
AU - Lanas, Angel
AU - Morton, Dion G.
AU - Riddell, Robert
AU - Iverson, Erik R.
AU - DeMets, David L.
N1 - Funding Information:
APPROVe was funded by Merck Research Laboratories. JAB, RSB, RSS, RR, DGM, and AL received consulting fees as members of the APPROVe Trial Steering Committee. JAB is a consultant to Bayer and has received research funding from the company. DLD consults extensively with NIH, FDA, and industry of clinical trials. In particular, he has obtained support for this analysis through a contract between the University of Wisconsin and Merck. ERI was supported by this same contract.
PY - 2008
Y1 - 2008
N2 - Background: Selective inhibition of cyclo-oxygenase-2 has been associated with an increased risk of cardiovascular events in several clinical trials. The Adenomatous Polyp Prevention on Vioxx (APPROVe) study assessed the effect of 3-year treatment with a cyclo-oxygenase-2 inhibitor, rofecoxib (25 mg), on recurrence of neoplastic polyps of the large bowel. We report the cardiovascular outcomes of a long-term follow-up of participants in the trial. Methods: The APPROVe study is a multicentre, randomised, placebo-controlled, double-blind trial. 2587 patients with a history of colorectal adenomas were recruited at 108 centres worldwide during 2000 and 2001. Participants were followed for adverse events while on treatment and during the following 14 days. However, after early termination of treatment because of cardiovascular toxicity, we attempted to follow up all randomised patients for at least 1 year after stopping study treatment. External committees blindly assessed potential serious cardiovascular events. The focus of the analysis was the combined incidence of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and unknown causes (Antiplatelet Trialists' Collaboration [APTC] combined endpoint). We used Cox proportional hazards regression to calculate endpoint hazard ratios. The study is registered with ClinicalTrials.gov, number NCT0282386. Findings: We obtained extended post-treatment cardiovascular follow-up data from 84% of participants, and extended mortality follow-up from 95%. In total, 59 individuals had an APTC endpoint in the rofecoxib group and 34 in the placebo group (hazard ratio 1·79, 95% CI 1·17-2·73; p=0·006). In the first year after cessation of treatment, there was a non-significant increase in the risks of APTC endpoints. The APTC hazard ratio did not substantially change over time. Interpretation: Use of rofecoxib is associated with increased rates of APTC events. Study data are compatible with an early increase in risk that persists for one year after stopping treatment. Funding: Merck Research Laboratories.
AB - Background: Selective inhibition of cyclo-oxygenase-2 has been associated with an increased risk of cardiovascular events in several clinical trials. The Adenomatous Polyp Prevention on Vioxx (APPROVe) study assessed the effect of 3-year treatment with a cyclo-oxygenase-2 inhibitor, rofecoxib (25 mg), on recurrence of neoplastic polyps of the large bowel. We report the cardiovascular outcomes of a long-term follow-up of participants in the trial. Methods: The APPROVe study is a multicentre, randomised, placebo-controlled, double-blind trial. 2587 patients with a history of colorectal adenomas were recruited at 108 centres worldwide during 2000 and 2001. Participants were followed for adverse events while on treatment and during the following 14 days. However, after early termination of treatment because of cardiovascular toxicity, we attempted to follow up all randomised patients for at least 1 year after stopping study treatment. External committees blindly assessed potential serious cardiovascular events. The focus of the analysis was the combined incidence of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and unknown causes (Antiplatelet Trialists' Collaboration [APTC] combined endpoint). We used Cox proportional hazards regression to calculate endpoint hazard ratios. The study is registered with ClinicalTrials.gov, number NCT0282386. Findings: We obtained extended post-treatment cardiovascular follow-up data from 84% of participants, and extended mortality follow-up from 95%. In total, 59 individuals had an APTC endpoint in the rofecoxib group and 34 in the placebo group (hazard ratio 1·79, 95% CI 1·17-2·73; p=0·006). In the first year after cessation of treatment, there was a non-significant increase in the risks of APTC endpoints. The APTC hazard ratio did not substantially change over time. Interpretation: Use of rofecoxib is associated with increased rates of APTC events. Study data are compatible with an early increase in risk that persists for one year after stopping treatment. Funding: Merck Research Laboratories.
UR - http://www.scopus.com/inward/record.url?scp=55749105531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55749105531&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(08)61490-7
DO - 10.1016/S0140-6736(08)61490-7
M3 - Article
C2 - 18922570
AN - SCOPUS:55749105531
SN - 0140-6736
VL - 372
SP - 1756
EP - 1764
JO - The Lancet
JF - The Lancet
IS - 9651
ER -