%0 Journal Article %1 RichardPeto09252008 %A Peto, Richard %A Emberson, Jonathan %A Landray, Martin %A Baigent, Colin %A Collins, Rory %A Clare, Robert %A Califf, Robert %D 2008 %J N Engl J Med %K Meta-analysis safety %N 13 %P 1357-1366 %R 10.1056/NEJMsa0806603 %T Analyses of Cancer Data from Three Ezetimibe Trials %U http://content.nejm.org/cgi/content/abstract/359/13/1357 %V 359 %X Background 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.

@article{RichardPeto09252008, abstract = {Background 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. }, added-at = {2008-09-26T12:00:06.000+0200}, author = {Peto, Richard and Emberson, Jonathan and Landray, Martin and Baigent, Colin and Collins, Rory and Clare, Robert and Califf, Robert}, biburl = {https://www.bibsonomy.org/bibtex/2ed5c933899545647645c1f508b532630/cucherat}, description = {NEJM -- Analyses of Cancer Data from Three Ezetimibe Trials}, doi = {10.1056/NEJMsa0806603}, eprint = {http://content.nejm.org/cgi/reprint/359/13/1357.pdf}, interhash = {d27b23595d010abfcd6b15b5cab802e6}, intrahash = {ed5c933899545647645c1f508b532630}, journal = {N Engl J Med}, keywords = {Meta-analysis safety}, number = 13, pages = {1357-1366}, timestamp = {2008-09-26T12:00:06.000+0200}, title = {{Analyses of Cancer Data from Three Ezetimibe Trials}}, url = {http://content.nejm.org/cgi/content/abstract/359/13/1357}, volume = 359, year = 2008 }