ACE研究将指导心血管疾病全面防治的新策略ppt课件

1、Professor Rury HolmanUniversity of Oxford, UKProfessor Chang Yu PanProfessor Da Yi HuChinese PLA General HospitalUniversity of PekingChinaChinaM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dRationale for ACE Trial Accumulating evidence suggests there is a close association between “

2、prediabetes and cardiovascular disease (CVD) Treating conventional risk factors in type 2 diabetes does not reduce CVD risk to the same level as in a non-diabetic population Post prandial hyperglycaemia may explain the excess risk seen in diabetes and “prediabetes Acarbose has been reported* to redu

3、ce CVD risk in individuals with “prediabetes, but its impact on new CVD events in individuals with “prediabetes and existing CVD and is unknown* Chiasson JL et al. JAMA 2003; 290(4): 486-94M a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dACE Trial ManagementCoordinating CentreDiabetes

4、 Trials Unit, University of OxfordACE Chinese Project OfficeOxford University () Science & Technology LimitedFunding & Study MedicationBayer HealthCare China & Bayer Schering PharmaM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dStudy DesignDouble-blind, multi-centre, ran

5、domised, controlled, clinical outcome trial comparing acarbose versus placebo Investigator designed and led academic trialIndependent data collection, analysis and reportingConducted in Mainland China and Hong Kong7,500 patients in 150 cardiovascular centresMinimum patient follow up four yearsEvent

6、driven (904 adjudicated primary events)M a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dRury HolmanUK Diabetologist (Chair)DaYi HuChina Cardiologist(Co-Chair)ChangYu PanChinaDiabetologist (Co-Chair)JiaLun ChenChinaDiabetologist (Honoured adviser)Juliana ChanHong Kong DiabetologistJean

7、-Louis ChiassonCanadaDiabetologistJunBo GeChinaCardiologistHertzel GersteinCanadaDiabetologistJohn McMurrayUKCardiologistLars RydnSwedenCardiologistMichal TenderaPoland CardiologistJaakko TuomilehtoFinlandEpidemiologistWenYing YangChinaDiabetologistJoanne KeenanUKDTU Project ManagerDieter NeuserGerm

8、anyBayer Project ManagerThorsten PetruschkeGermanyBayer Project ManagerACE Steering CommitteeM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dMajor Inclusion CriteriaConfirmed cardiovascular disease (CVD)History of myocardial infarctionPrevious unstable anginaCurrent stable anginaImpa

9、ired glucose tolerance (IGT) on an oral glucose tolerance test with:Fasting plasma glucose 3x ULN)Severe renal impairment(eGFR 30 ml/min/1.73m2)Gastrointestinal problems or alpha glucosidase inhibitor intolerancePregnancy or possibility of pregnancyThought by the investigator to be unsuitableM a c i

10、n to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dACE Primary EndpointComposite “hard CVD endpointDefined as the time to the first occurrence after randomisation of any of:Cardiovascular deathResuscitated cardiac arrestNon-fatal myocardial infarctionNon-fatal strokeAn Endpoint Adjudication Co

11、mmittee, masked to therapy allocation, will review all potential CVD endpoints independently.M a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dNew-onset type 2 diabetes, confirmed by two successive diagnostic plasma glucose valuesFPG 7.0 mmol/land/or2HPG 11.1 mmol/lACE Secondary Endpoi

12、ntM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte d All cause mortality Extended CVD endpoint of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, fatal or non-fatal stroke and hospitalisation for heart failure or for unstable angina. Each component w

13、ill also be analysed individually Evidence of non-alcoholic fatty liver disease (NAFLD) as judged by ALT changes Development of impaired renal function (eGFR 60 ml/minute/1.73 m2) or doubling of baseline creatinine Health Economic evaluationOther Secondary OutcomesM a c in to s h P IC Tim a g e fo r

14、m a tis n o t s u p p o rte dSample Size EstimationAssumesA primary event rate of 3.5% per yearA 20% relative reduction compared with placeboAn 18 month accrual periodAlpha of 5%For 90% PowerThe study requires 7,268 patients with a minimum of 904 adjudicated primary events A total of 7,500 patients

15、will be recruited to allow for an overall 3% loss-to-follow upM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dDouble Blind InterventionIn addition to optimised CVD therapy:Randomised to:Acarbose, 50 mg three times a dayorMatching placebo, three times a dayTablets to be taken with mea

16、lsUse Start low, go slow dose titrationM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dACE Study Flow ChartM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dMinimum of 904 adjudicated primary events required7,500CVDor ACSOptimisation of Cardiovascular TherapyCVD therapy

17、 will be optimised during the four-week, single-blind, placebo run-in period to ensure it conforms with international guidelines for treating patients with established CVDThat is:Antiplatelet therapy, unless contraindicated or not toleratedA statin, unless contraindicated or not toleratedACE inhibit

18、or, beta-blocker, and/or antihypertensive therapy if considered indicated by the investigatorM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dSafetyThe ACE trial will be conducted to ICH-GCP standardsLiver function will be monitored annuallySerious Unexpected Suspected Adverse Reactio

19、ns (SUSARs) will undergo expedited reportingAn Independent Data Safety Monitoring Board (DSMB) will review unblinded safety data at least six-monthlyM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dThe ACE trial is enrolling 150 cardiovascular centres in Mainland China and Hong KingEach centre is expected to recruit approximately 50 patients (minimum of 35 patients)Recruitment is competitive and will close when 7,500 patients have been randomisedThe ACE trial results are expected in 2021ScheduleClinical Centre RequirementsQualified resea