New results from an observational sub-study from TRITON—TIMI 38 presented at the American Heart Association (AHA) Scientific Sessions annual meeting showed that patients treated with Effient (prasugrel) prior to coronary artery bypass graft surgery (CABG) had a reduced overall mortality rate compared to patients treated with Plavix (clopidogrel) (2.3 per cent versus 8.7 per cent respectively, p=0.016).
This retrospective analysis involved 346 patients with acute coronary syndrome (ACS) who had received either study drug and subsequently underwent isolated CABG at some point during the 15-month TRITON-TIMI 38 trial.
In addition to all-cause mortality, this same 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 per cent versus 5.8 per cent respectively, p=0.038). Effient-treated patients experienced a statistically significantly higher volume of chest tube blood loss at 12 hours post-CABG compared to the clopidogrel-treated patients (655 +/- 580 milliliters with Effient versus 503 +/- 378 milliliters with clopidogrel).
"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," said Peter K. Smith, M.D., professor of surgery and division chief of Cardiovascular and Thoracic Surgery at Duke University Medical Center and lead investigator for the retrospective CABG analysis. "This analysis helps better define the risk of mortality for physicians who care for the ACS patients who may be targeted for percutaneous coronary intervention (PCI) but end up undergoing CABG instead."
The Effient prescribing information includes a warning and precaution against starting Effient in patients likely to undergo urgent CABG surgery. The risk of bleeding is increased in patients receiving Effient who undergo CABG. If possible, Effient should be discontinued at least seven days prior to CABG.
TRITON-TIMI 38 was a phase III, randomized, double-blind, head-to-head clinical trial comparing the effects of Effient versus clopidogrel in patients with ACS who were managed with PCI, a procedure to open blockages in heart arteries, 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, non-fatal heart attack or non-fatal stroke during at least 12 months following 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).
This retrospective analysis included newly collected data on 346 patients who underwent isolated CABG following withdrawal of study drug, either Effient (n=173) or clopidogrel n=173), during the TRITON-TIMI 38 study. Possible baseline imbalances between arms were adjusted using European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Society of Thoracic Surgeons (STS) 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 non-randomized comparison between Effient and clopidogrel may be subject to potential residual biases.
Daiichi Sankyo Company, Limited, and Eli Lilly and Company co-developed Effient, an oral antiplatelet agent discovered by Daiichi Sankyo and its Japanese research partner, Ube Industries, Ltd. Effient helps keep blood platelets from clumping together and developing a blockage in an artery. Effient is approved by the US Food and Drug Administration for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with ACS who are managed with an artery-opening procedure known as PCI. PCI usually includes the placement of a stent to help keep the artery open.