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1、Prasugrel vs. Clopidogrel for Acute Coronary Syndromes Patients Managed without Revascularization the TRILOGY ACS trialOn behalf of the TRILOGY ACS Investigatorswww.clinicaltrials.govwww.clinicaltrials.gov Identifier: NCT00699998 Identifier: NCT00699998Committees and DisclosuresExecutive Committee M
2、agnus Ohman, MB ChB Chair Matthew Roe, MD PI Paul Armstrong, MD Keith Fox, MB ChB Harvey White, MB ChB Dorairaj Prabhakaran, MDData Monitoring Board Frans van de Werf, MD Chair Bernard Gersh, MB ChB Robert Wilcox, MB ChB Stuart Pocock, Ph.D. David Williams, MD Andrzej Budaj, MD Gilles Montalescot, M
3、D Michael Wilson, MSSteering Committee 50 representatives from the participating countries Conflict of Interest Disclosures Disclosures for Drs. Roe and Ohman listed on www.dcri.org Disclosures for all authors listed within the manuscriptTrial Conduct Academic Coordinating Center: DCRI Independently
4、 performed statistical analyses Global project management Event adjudication activities Global Trial Operations: Quintiles Site management Data management Sponsors: Eli Lilly and Daiichi Sankyo Protocol Adherence Total of 18 patients lost to follow-up (0.2% of overall) Median study follow-up: 17.1 m
5、onths (10.4, 24.4)TRILOGY ACS Background The proportion of ACS (UA/NSTEMI) patients world -wide who are managed medically without revascularization (PCI or CABG) is 40-60% Medically managed ACS patients have a two-fold increase in ischemic events, but have been under- represented in contemporary ACS
6、 trials Prasugrel, a thienopyridine P2Y12 inhibitor, was shown to improve outcomes compared with clopidogrel in ACS patients undergoing PCI in the TRITON trial, with an increase in major bleedingTRILOGY ACS Inclusion Criteria Randomization within 10 days of a UA/NSTEMI event NSTEMI: CK-MB or Troponi
7、n ULN UA: ST depression 1 mm in 2 or more leads “Reasonable certainty” for a medical management strategy decision determined Angiography not required, but if performed, had to be done before randomization, and evidence of coronary disease had to be seen (1 lesion 30% or prior PCI/CABG) At least 1 of
8、 4 enrichment criteria: Age 60 years Diabetes Mellitus Prior MI Prior Revascularization (PCI or CABG)TRILOGY ACS Study DesignMedically Managed UA/NSTEMI PatientsClopidogrel175 mg MDPrasugrel1 5 or 10 mg MDMinimum Rx Duration: 6 months; Maximum Rx Duration: 30 monthsPrimary Efficacy Endpoint: CV Deat
9、h, MI, Stroke Randomization Stratified by: Age, Country, Prior Clopidogrel Treatment (Primary analysis cohort Age 1 Year: 0.72 (0.54, 0.97)Primary Efficacy Endpoint to 30 Months (Age 1 YearCV Death1.00 (0.78, 1.28)0.75 (0.49, 1.14)All MI0.97 (0.78, 1.19)0.68 (0.46, 0.99)All Stroke0.86 (0.50, 1.47)0.
10、35 (0.14, 0.88)HR: 0.93 (0.75-1.15)HR: 0.89 (0.74-1.07)HR: 0.67 (0.42-1.06)CV DeathAll MIAll StrokeEvaluation of All Ischemic Events Over Time* (Age 12 mos = 0.64, 95% CI: 0.480.86, Interaction P=0.02) * Pre-specified evaluation of all CV death, MI, or stroke events by treatmentTIMI Major Bleeding t
11、o 30 Months (Age 75 years)HR (95% CI): 1.31 (0.81, 2.11) P = 0.27Incidence of Bleeding Outcomes (Age 75 years)GUSTO CriteriaP = 0.06P = 0.8752133514TIMI CriteriaP = 0.02P = 0.39P = 0.99P = 0.88P = 0.2770841639461241730Primary Efficacy Endpoint and TIMI Major Bleeding Through 30 Months (Overall popul
12、ation)HR (95% CI): 0.96 (0.86, 1.07) P = 0.45HR (95% CI): 1.23 (0.84, 1.81) P = 0.29Incidence of Key Safety Outcomes (Overall Population)Prasugrel ClopidogrelHazard Ratio (95% CI)P ValueBleeding(N = 4623) (N = 4617)GUSTO Severe/life-threatening bleeding22 (0.5%)27 (0.6%)0.83 (0.481.46)0.53TIMI Fatal
13、 Bleeding7 (0.2%)9 (0.2%)0.80 (0.302.14)0.68Intracranial Hemorrhage14 (0.3%)19 (0.4%)0.76 (0.381.51)0.42NeoplasmNew, non-benign neoplasms*82 (1.8%)78 (1.7%)1.05 (0.77-1.43)0.79Mortality(N = 4663) (N = 4663)All-cause death385 (8.3%)409 (8.8%)0.94 (0.821.08)0.40*Among patients with no prior history of
14、 malignancy or prior malignancy treated with curative therapy Conclusions In the largest trial to date of ACS patients managed medically without revascularization, prasugrel was not statistically different from clopidogrel during 2.5 years of follow-up among patients 75 years of age Further analyses
15、 of the primary endpoint yielded several important findings favoring prasugrel treatment Trend for a time-dependent benefit after 1 year Fewer total recurrent ischemic events, particularly after 1 year No statistical differences in major, life-threatening, or fatal bleeding with prasugrel vs. clopidogrelwww.nejm.org - 8.26.12
