Effient Shown to Lower Mortality Rates in CABG Patients

November 16, 2010—Daiichi Sankyo Company, Ltd. (Tokyo, Japan) and Eli Lilly and Company (Indianapolis, IN) announced that new results from an observational substudy from TRITON-TIMI 38 showed that patients treated with the companies' Effient (prasugrel) before coronary artery bypass graft surgery (CABG) had a reduced overall mortality rate compared to patients treated with clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, New York, NY) (2.3% vs 8.7%, respectively; P = .016). Effient is an oral antiplatelet agent that is approved by the US Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndromes (ACS) who are managed with percutaneous coronary intervention (PCI).

This retrospective analysis involved newly collected data on 346 patients with ACS who had received either study drug (Effient, n = 173; or clopidogrel, n = 173) and subsequently underwent isolated CABG after withdrawal of the drug at some point during the 15-month TRITON-TIMI 38 trial. The data were presented at the American Heart Association (AHA) Scientific Sessions 2010 in Chicago. Peter K. Smith, MD, is lead investigator for the retrospective CABG analysis.


“This analysis showed that Effient was associated with a significantly lower mortality rate compared with clopidogrel among these CABG patients but with a significantly higher risk of serious bleeding events,” commented Dr. Smith. “This analysis helps better define the risk of mortality for physicians who care for the ACS patients who may be targeted for PCI but end up undergoing CABG instead.”


In addition to all-cause mortality, this analysis found that the risk-adjusted rate of cardiovascular death at 30 days was also lower in patients treated with Effient compared with those receiving clopidogrel (0.6% vs 5.8%, respectively; P = .038). Effient-treated patients experienced a statistically significantly higher volume of chest tube blood loss at 12 hours after CABG compared to the clopidogrel-treated patients (655 ± 580 mL with Effient vs 503 ± 378 mL with clopidogrel).



TRITON-TIMI 38 was a phase 3, randomized, double-blind, head-to-head clinical trial comparing the effects of Effient versus clopidogrel in patients with ACS who were managed with PCI, including the use of coronary stenting. The study enrolled 13,608 patients at 707 trial sites in 30 countries.

The primary endpoint of the study was the combined incidence of cardiovascular death, nonfatal heart attack, or nonfatal stroke during at least 12 months after PCI. Patients were randomly assigned to one of two treatment groups and given a loading dose of either Effient 60 mg or the FDA-approved loading dose of clopidogrel 300 mg, followed by a daily maintenance dose of either Effient 10 mg or clopidogrel 75 mg. All patients also received a daily dose of aspirin (75 mg to 325 mg). 



Possible baseline imbalances between arms were adjusted using European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Society of Thoracic Surgeons scoring, two widely accepted and standardized methods of calculating cardiac operative mortality risk. Bleeding was measured by chest tube blood loss, a standard method used by surgeons. Despite the adjustment for predicted risk of mortality at the time of CABG, this nonrandomized comparison between Effient and clopidogrel may be subject to potential residual biases, the companies advised.