HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Analyses of cancer data from three ezetimibe trials.

AbstractBACKGROUND:
Five years of statin therapy lowers low-density lipoprotein (LDL) cholesterol substantially and, over a 5-year period, results in reductions in the incidence of cardiovascular events. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (ClinicalTrials.gov number, NCT00092677) has raised the hypothesis that adding ezetimibe to statin therapy for larger LDL cholesterol reductions might increase the incidence of cancer.
METHODS:
We compared the results of a hypothesis-generating analysis of the incidence of cancer in the SEAS trial of ezetimibe plus simvastatin in 1873 patients (mean follow-up after ezetimibe or matching placebo was begun, 4.1 years) with a hypothesis-testing analysis of cancer data from the two large ongoing trials of this regimen: the Study of Heart and Renal Protection (SHARP) (NCT00125593) with 9264 patients (mean follow-up, 2.7 years) and the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) (NCT00202878), currently with 11,353 patients (mean follow-up, 1.0 year).
RESULTS:
In the SEAS trial, assignment to ezetimibe was associated with an increase in any new onset of cancer (101 patients in the active-treatment group vs. 65 in the control group) from several cancer sites. In SHARP and IMPROVE-IT combined, there was no overall excess of cancer (313 active-treatment vs. 326 control; risk ratio, 0.96; 95% confidence interval, 0.82 to 1.12; P=0.61) and no significant excess at any particular site. Among patients assigned to ezetimibe, there were more, albeit not significantly more, deaths from cancer (97, vs. 72 in the control group; P=0.07), but there were also fewer, although not significantly fewer, other cases of cancer (216, vs. 254 in the control group; P=0.08). There was no evidence of a trend in the risk ratio for incidence of or death from cancer with increasing duration of follow-up.
CONCLUSIONS:
The available results from these three trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer. Follow-up of longer duration will permit the balance of risks and benefits to be determined more reliably.
AuthorsRichard Peto, Jonathan Emberson, Martin Landray, Colin Baigent, Rory Collins, Robert Clare, Robert Califf
JournalThe New England journal of medicine (N Engl J Med) Vol. 359 Issue 13 Pg. 1357-66 (Sep 25 2008) ISSN: 1533-4406 [Electronic] United States
PMID18765432 (Publication Type: Comment, Comparative Study, Journal Article)
Copyright2008 Massachusetts Medical Society
Chemical References
  • Anticholesteremic Agents
  • Azetidines
  • Cholesterol, LDL
  • Simvastatin
  • Ezetimibe
Topics
  • Anticholesteremic Agents (adverse effects, therapeutic use)
  • Aortic Valve Stenosis (drug therapy)
  • Azetidines (adverse effects, therapeutic use)
  • Cholesterol, LDL (blood)
  • Drug Therapy, Combination
  • Ezetimibe
  • Follow-Up Studies
  • Humans
  • Hypercholesterolemia (drug therapy)
  • Incidence
  • Neoplasms (chemically induced, epidemiology)
  • Randomized Controlled Trials as Topic
  • Risk
  • Simvastatin (adverse effects, therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: