Fractional Flow Reserve Guided PCI versus Medical Therapy in Stable Coronary Disease. FAME 2 Trial

Transcription

1 Fractional Flow Reserve Guided PCI versus Medical Therapy in Stable Coronary Disease FAME 2 Trial Clinicaltrials.gov NCT Bernard De Bruyne, Nico H.J. Pijls, William F Fearon, Peter Juni, Emanuele Barbato, Pim Tonino, for the FAME 2 study group

2 Potential conflicts of interest Speaker s name: Bernard De Bruyne I have the following potential conflicts of interest to report: Research contracts Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest Study Supported by St. Jude Medical

3 Background In patients with stable coronary disease, PCI has not been shown to improve prognosis FAME 1 demonstrated the superiority of FFR-guided over angiography-guided PCI In previous trials, revascularization has been guided by the angiographic appearance of the lesions It is likely that in previous trials a sizable proportion of patients had no or little ischemia

4 Objective To compare clinical outcomes of FFRguided contemporary PCI plus the best available medical therapy (MT) versus MT alone in patients with stable coronary disease

5 Inclusion Criteria Referred for PCI because of And Stable angina pectoris (CCS 1, 2, 3) Stabilized angina pectoris CCS class 4 Atypical or no chest pain with documented ischemia Angiographic 1, 2, or 3 vessel disease

6 Exclusion Criteria 1. Prior CABG 2. LVEF < 30% 3. LM disease

7 Primary End Point Composite of all cause death myocardial infarction unplanned hospitalization with urgent revascularization

8 Flow Chart Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI N = 1220 Randomized Trial FFR in all target lesions Registry At least 1 stenosis with FFR 0.80 (n=888) When all FFR > 0.80 (n=332) Randomization 1:1 PCI + MT 73% MT 27% MT 50% randomly assigned to FU Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years

9 Study Centers (n=28) Investigators Centers # of Patients Piroth Hungarian Institute of Cardiology- Hungary 145 Jagic Clinical Center Kragujevac- Serbia 132 Mobius-Winkler Heart Center Leipzig- Germany 131 Pijls Catherina-Ziekenhuis- The Netherlands 89 Rioufol Hospices Civil de Lyon- France 86 Witt Sodersjukhuset- Sweden 85 De Bruyne Cardiovascular Center Aalst- Belgium 82 Kala University Hospital Brno- Czech Republic 75 Fearon Stanford Univ/VA Med Center Palo Alto- USA 50 MacCarthy Kings College Hospital- UK 42 Engstroem Rigshospitalet University Hospital- Denmark 42 Oldroyd Golden Jubilee National Hospital- UK 37 Mavromatis Atlanta VA Medical Center- USA 34 Manoharan Royal Victoria Hospital- Ireland 27 9

10 Study Centers (n=28) Investigators Centers # of Patients Ver Lee Northeast Cardiology Associates- USA 25 Frobert Orebro University Hospital- Sweden 25 Curzen Southampton General Hospital- UK 18 Sohn Klinikum der Universitat Munchen- Germany 18 Uren Edinburgh Heart Center- Scotland 12 Samady Emory University- USA 12 Dambrink Isala Klinieken- Netherlands 12 Mansour CHUM - Hotel Dieu- Canada 11 Arain Tulane University- USA 8 Mates Nemocnice Na Homolce- Czech Republic 8 Rensing St. Antonius Ziekenhuis- Netherlands 5 Valgimigli Universitaria de Ferrara- Italy 4 Rieber Heart Center Munich- Germany 3 Schampaert Hopital du Sacre Coeur- Canada 2 10

11 DSMB Recommendation On recommendation of the independent Data and Safety Monitoring Board* recruitment was halted on January 15 th, 2012 after inclusion of 1220 patients (± 54% of the initially planned number of randomized patients) *DSMB: Stephan Windecker, Chairman, Stuart Pocock, Bernard Gersh 11

12 Baseline Clinical Characteristics (1) Randomized trial N=888 Registry N=322 P* Patients, N PCI+MT=447 MT=441 with FU=166 Demographic Age (y) 63.5± ± ± Male sex - (%) BMI 28.3± ± ± Risk factors for CAD Positive family history CAD - (%) Smoking - (%) Hypertension - (%) Hypercholesterolemia - (%) Diabetes mellitus - (%) Insulin requiring diabetes - (%) *P value compares all RCT patients with patients in registry 12

13 Baseline Clinical Characteristics (2) Randomized trial N=888 Registry N=322 P* Patients, N PCI+MT=447 MT=441 with FU=166 Non-Cardiac Co-Morbidity Renal Failure (Cr > 2.0 mg/dl) - (%) History of stroke or TIA - (%) Peripheral vascular disease - (%) Cardiac History History of MI - (%) History of PCI in target vessel -(%) Angina - (%) 0.64 Asymptomatic CCS class I CCS class II CCS class III CCS class IV, stabilized Silent ischemia- (%) LVEF < 50% - (%) *P value compares all RCT patients with patients in registry 13

14 Angiographic Characteristics Randomized trial N=888 Registry N=322 P* Patients, N PCI+MT=447 MT=441 with FU=166 Angiographically significant stenoses - no. per patient 1.87± ± ±0.59 <0.001 No of vessels with 1 significant stenoses - (%) <0.001 Prox- or mid- LAD stenoses - (%) <0.001 *P value compares all RCT patients with patients in registry 14

15 FFR Measurements Randomized trial N=888 Registry N=322 P* Patients, N PCI+MT=447 MT=441 with FU=166 FFR significant stenoses - no. per patient 1.52± ± ±0.17 <0.001 No of vessels with 1 significant stenoses (by FFR) - (%) Prox- or mid- LAD stenoses - (%) <0.001 Lesions with FFR (%) ** <0.001 Mean FFR in stenoses with FFR ± ± ± * P value compares all RCT patients with patients in registry ** Chronic occlusions in the registry patients were arbitrarily assigned an FFR value of These patients also had another lesion >50% with an FFR >

16 Cumulative incidence (%) FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Primary Outcomes PCI+MT vs. MT: HR 0.32 ( ); p<0.001 PCI+MT vs. Registry: HR 1.29 ( ); p=0.61 MT vs. Registry: HR 4.32 ( ); p< No. at risk MT PCI+MT Registry Months after randomization

17 Cumulative incidence (%) FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Death from any Cause PCI+MT vs. MT: HR 0.33 ( ); p=0.31 PCI+MT vs. Registry: HR 1.12 ( ); p=0.54 MT vs. Registry: HR 2.66 ( ); p= No. at risk MT PCI+MT Registry Months after randomization

18 Cumulative incidence (%) FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Myocardial Infarction PCI+MT vs. MT: HR 1.05 ( ); p=0.89 PCI+MT vs. Registry: HR 1.61 ( ); p=0.41 MT vs. Registry: HR 1.65 ( ); p= No. at risk MT PCI+MT Registry Months after randomization

19 Cumulative incidence (%) FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Urgent Revascularization PCI+MT vs. MT: HR 0.13 ( ); p<0.001 PCI+MT vs. Registry: HR 0.63 ( ); p=0.43 MT vs. Registry: HR 4.65 ( ); p= No. at risk MT PCI+MT Registry Months after randomization

20 Patients with urgent revascularization Unstable angina only 51.8% 21.4% 26.8% Myocardial Infarction Unstable angina +evidence of ischemia on ECG

21 Cumulative incidence (%) Cumulative (%) FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Kaplan-Meier plots of Landmark Analysis of Death or MI days: HR 7.99 ( ); p=0.038 > 8 days: HR 0.42 ( ); p=0.053 p-interaction: p= Days after randomization >8 days PCI plus MT MT alone 7 days 0 7days Months after randomization MT alone PCI plus MT

22 Proportion of patients (%) Medications at 6 Months of Follow-up PCI + MT MT alone Registry

23 Patients with Angina Class II to IV Baseline PCI+MT MT Registry 30 days PCI+MT MT Registry P<0.001 P= months PCI+MT MT Registry P= months PCI+MT MT Registry P= Percentage of patients with CCS II to IV, %

24 Conclusions In patients with stable coronary artery disease, FFR-guided PCI, improves patient outcome as compared with medical therapy alone This improvement is driven by a dramatic decrease in the need for urgent revascularization for ACS In patients with functionally non-significant stenoses medical therapy alone resulted in an excellent outcome, regardless of the angiographic appearance of the stenoses

25 FAME 2: FFR-Guided PCI versus Medical Therapy in Stable CAD Available on-line on Aug 28, 2012 on