Inpharma 1655 - 13 Sep 2008

Apixaban advantageous in ACS?The investigational factor Xa inhibitor apixaban* has

demonstrated potential for the prevention of myocardialinfarction (MI) and stroke among patients with acutecoronary syndrome (ACS), according to phase II studyresults presented at the Annual Congress of theEuropean Society of Cardiology.

The 6-month APPRAISE-1 trial** was a placebo-controlled, dose-ranging study, designed to test thesafety and efficacy of apixaban in patients with ACS. Atotal of 1715 such patients, from 14 countriesthroughout Europe and North America, wererandomised to receive apixaban at a dose of 2.5mg twicedaily, 10mg once daily, 10mg twice daily, 20mg oncedaily or placebo, for 26 weeks. In addition, all patientsreceived aspirin ≤ 165 mg/day; the use of clopidogrelwas left to the discretion of the treating physician. Theprimary endpoint of the study was the incidence ofmajor bleeding and clinically relevant non-majorbleeding, as defined using International Society ofThrombosis and Haemostasis (ISTH) standard criteria.The composite efficacy endpoint was the time to firstoccurrence of cardiovascular death, non-fatal MI, non-haemorrhagic stroke and severe recurrent ischaemia.

The two arms of the study that evaluated apixaban atdoses of 10mg twice daily and 20mg once daily werediscontinued early due to an increased total risk ofbleeding. The incidence of the primary safety endpointwas 5.7% for apixaban 2.5mg twice daily recipients,7.9% for 10mg once daily recipients, and 3.0% forplacebo recipients. The incidence of major ISTHbleeding was 0.8% with placebo, 1.6% with apixaban2.5mg twice daily, and 1.9% with apixaban 10mg oncedaily.

Results not so convincingFor the composite efficacy endpoint, there was a non-

significant relative risk reduction of 27% with apixaban2.5mg twice daily and 39% with apixaban 10mg oncedaily, compared with placebo.

"The data show adding 5 or 10 milligrams of apixabanto a regimen of aspirin or aspirin and clopidogrel inpatients hoping to prevent a second heart attack mayoffer therapeutic potential", commented lead researcherDr John Alexander, Duke University Medical Center."But this needs to be definitively demonstrated in astatistically significant manner in large, well-controlledstudies", he concluded.* Bristol-Myers Squibb, Pfizer; phase II for ACS, phase III forthrombosis and stroke in several countries** sponsored by Bristol-Myers Squibb

Bristol-Myers Squibb Company, et al. New Data is Presented on InvestigationalOral Anticoagulant Apixaban in Acute Coronary Syndrome Patients. MediaRelease : 2 Sep 2008. Available from: URL: http://www.bms.com 809092712

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Inpharma 13 Sep 2008 No. 16551173-8324/10/1655-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved