Abstract | BACKGROUND: 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.
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Authors | Richard Peto, Jonathan Emberson, Martin Landray, Colin Baigent, Rory Collins, Robert Clare, Robert Califf |
Journal | The 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 |
PMID | 18765432
(Publication Type: Comment, Comparative Study, Journal Article)
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Copyright | 2008 Massachusetts Medical Society |
Chemical References |
- Anticholesteremic Agents
- Azetidines
- Cholesterol, LDL
- Simvastatin
- Ezetimibe
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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)
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