Randomized Comparison of Percutaneous Mitral Valve Repair and Surgery for Mitral Regurgitation

Transcription

1 Randomized Comparison of Mitral Valve Repair and for Mitral Regurgitation 2 Year Results of the EVEREST II Randomized Controlled Trial Ted Feldman, Elyse Foster, Saibal Kar, William Gray, Andrew Wang, Howard Herrmann, Paul Grayburn, John Lasala, Reginald Low, Tanvir Bajwa, Wesley Pedersen, Donald Glower and Laura Mauri on behalf of the EVEREST II Investigators

2 Disclosures Research Grants Abbott Vascular, Boston Scientific, Edwards Consultant Abbott Vascular, Boston Scientific, Edwards 2

3 Mitral Valve Repair MitraClip System

4 Introduction EVEREST II Randomized Controlled Trial Outcomes through 1 year have been previously reported MitraClip device demonstrated increased safety compared to surgery reduced MR more than percutaneous procedure 77% of percutaneous vs. 100% of surgical patients had inhospital MR reduction to 2+ or less Both groups showed improved LV function, NYHA Functional Class and Quality of Life We report 2 year clinical outcomes for the EVEREST II Randomized Controlled Trial

5 Study Organization EVEREST II RCT Principal Investigators: Ted Feldman, MD Evanston NorthShore University HealthSystem Donald Glower, MD Duke University Medical Center Academic Research Organization: Laura Mauri, MD Harvard Clinical Research Institute Data Safety Monitoring Board: Richard Shemin, MD University of California, Los Angeles Clinical Events Committee: Don Cutlip, MD Harvard Clinical Research Institute Echocardiography Core Lab: Elyse Foster, MD University of California, San Francisco Sponsor: Abbott Vascular Menlo Park, CA 5

6 EVEREST II RCT Investigators T Feldman, J Alexander, R Curran, E Chedrawy, S Smart, M Lampert NorthShore University HealthSystem, Evanston, IL A Wang, D Glower, J Jollis Duke University, Durham, NC T Byrne, P Tibi, HK Fang, JM Morgan Banner Good Samaritan Medical Center, Phoenix, AZ R Quesada, J Lamelas, N Moreno, R Machado Baptist Hospital of Miami, Miami, FL P Grayburn, B Hamman, R Hebeler, M Mack, W Ryan Baylor University Medical Center, Dallas, TX A Eisenhauer, M Davidson, L Cohn, J Wu Brigham and Women s Hospital, Boston, MA J Hermiller, D Heimansohn, K Allen, D Segar The Care Group, Indianapolis, IN M Rinaldi, E Skipper, R Steigel, J Cook, G Rose Carolinas Medical Center, Charlotte, NC S Kar, G Fontana, A Trento, R Kass, W Cheng, R Siegel, K Tolstrup Cedars-Sinai Medical Center, Los Angeles, CA P Whitlow, T Mihaljevic, N Smidera, L Svenssen, E Roselli, L Rodriquez, W Stewart The Cleveland Clinic, Cleveland, OH H Wasserman, W Gray, A Stewart, M Williams, M Argenziano, S Homma, R Pizzarello, L Gillam Columbia University, New York, NY; Danville, CT P Block, Z Ghazzal, T Vassiliades, R Martin, J Merlino, S Lerakis Emory University Hospital, Atlanta, GA B Whisenant, S Clayson, B Reid, S Horton, J Orford Latter Day Saints Hospital, Salt Lake City, UT R Smalling, G Letsou, J Walkes, C Loghin Memorial Hermann Hospital, Houston, TX W Pedersen, V Kshettry, F Eales, T Flavin, T Kroshus, R Bae Minneapolis Heart Institute, Minneapolis, MN O Nass, D Gangahar, R Jex, R Kacere Nebraska Heart Institute, Lincoln, NE SC Wong, OW Isom, L Girardi, K Krieger, R Devereux, R Mishra New York Presbyterian Hospital, New York, NY J Slater, A Galloway, G Perk, I Kronzon NYU Medical Center, New York, NY S Ramee, C Van Meter, P Parrino, C Lavie, Y Gilliland, VS Lucas Ochsner Clinic Foundation, New Orleans, LA R Kipperman, S Lucas, RM Bodenhamer, J Randolph, J Williams Oklahoma Heart Hospital, Okalahoma City, OK R Leung, R MacArthur, J Mullen, D Ross, J Choy Royal Alexandra Hospital, Edmonton, AB, Canada P Kramer, B Castlemain, A Schwartz, L Crouse, V Pasnoori Shawnee Mission Medical Center, Shawnee Mission, KS A Berke, N Robinson, R Colangelo, P Damus, H Fernandez, J Taylor, N Bercow, A Katz St. Francis Hospital, Long Island, NY M O'Donnell, M Qureshi, A Pruitt, B Kong, B McAllister, S Girard St. Joseph s Mercy Hospital, Ypsilanti, MI T Bajwa, D O Hair, D Kress, K Sagar St. Luke s Medical Center, Milwaukee, WI JT Maddux, M Sanz, S Tahta, JM Maxwell, B Berry, J Knapp St. Patrick's Hospital & Health Science Ctr, Missoula, MT W Gray, M Reisman, W Curtis, D Gartman, J Teply, D Warth, K Krabill Swedish Medical Center, Seattle, WA P Fail, K Paape, T Fudge, M Trotter, M Allam, E Feinberg, V Tedesco, D Solet Terrebonne General Medical Center, Houma, LA E Horlick, T David, M Borger, M Mezody Toronto General Hospital, Toronto, ON, Canada R Low, N Young, K Shankar, R Calhoun, W Bommer University of California at Davis, Sacramento, CA J Carroll, J Cleveland, R Quaife University of Colorado Health Sciences Center, Denver, CO H Herrmann, M Acker, YJ Woo, F Silvestry, S Wiegers University of Pennsylvania, Philadelphia, PA S Bailey, E Sako, J Erikson University of Texas Health Sciences Ctr, San Antonio, TX DS Lim, I Kron, J Kern, J Dent, H Gutgesell University of Virginia, Charlottesville, VA E Fretz, J Ofiesh, M Mann Victoria Heart Institute Foundation, Victoria BC, Canada K Kent, S Boyce. P Sears-Rogan Washington Hospital Center, Washington DC J Lasala, M Moon, R Damiano, B Lindman, A Zajarias, J Madrazo Washington University Medical Center, St. Louis, MO G Hanzel, F Shannon, M Sakwa, A Abbas, M Gallagher, P Markovitz William Beaumont Hospital, Royal Oak, MI Interventional Cardiologist, Cardiac Surgeon, Echocardiologist 6

7 Key Inclusion/Exclusion Criteria EVEREST II RCT Inclusion Candidate for MV Moderate to severe (3+) or severe (4+) MR Symptomatic o >25% EF & LVESD 55mm Asymptomatic with one or more of the following o LVEF 25-60% o LVESD 40mm o Pulmonary hypertension o Atrial fibrillation ACC/AHA Guidelines JACC 52:e1-e142, 2008 Exclusion AMI within 12 weeks Need for other cardiac surgery Renal insufficiency Creatinine >2.5mg/dl Endocarditis Rheumatic heart disease MV anatomical exclusions Mitral valve area <4.0cm 2 Leaflet flail width ( 15mm) and gap ( 10mm) Leaflet tethering/coaptation depth (>11mm) and length (<2mm) 7

8 Study Design EVEREST II Randomized Controlled Trial (RCT) 279 Patients enrolled at 37 sites Significant MR (3+ or 4+) Specific Anatomical Criteria Randomized 2:1 Group MitraClip System N=184 Group Surgical Repair or Replacement N=95 Echocardiography Core Lab and Clinical Follow-Up: Baseline, 30 days, 6 months, 1 year, 18 months, and annually through 5 years 8

9 Baseline Demographics & Co-morbidities Intention to Treat Patient Demographics % N=184 % N=95 P-value Age (mean) 67 years 66 years 0.32 Male History of CHF Coronary artery disease >0.99 Prior myocardial infarction >0.99 Previous cardiovascular surgery Atrial fibrillation COPD (with or without home O 2 ) >0.99 Moderate to Severe Renal Failure Diabetes

10 Baseline Demographics & Co-morbidities Intention to Treat Patient Demographics % N=184 % N=95 P-value Degenerative MR Etiology Anterior leaflet involvement (prolapse or flail) Posterior leaflet involvement only (prolapse or flail) Neither prolapse nor flail (thickened leaflets) Functional MR Etiology NYHA Functional Class III/IV MR Severity: 3+ to Mean Ejection Fraction (%) Mean LVIDs (cm)

11 Safety Endpoint: 30 Day MAE Intention to Treat # (%) Patients experiencing event 30 Day MAE (N=180) (N=94) Death 2 (1.1%) 2 (2.1%) Major Stroke 2 (1.1%) 2 (2.1%) Re-operation of Mitral Valve 0 1 (1.1%) Urgent / Emergent CV 4 (2.2%) 4 (4.3%) Myocardial Infarction 0 0 Renal Failure 1 (0.6%) 0 Deep Wound Infection 0 0 Ventilation > 48 hrs 0 4 (4.3%) New Onset Permanent Atrial Fib 2 (1.1%) 0 Septicemia 0 0 GI Complication Requiring 2 (1.1%) 0 Transfusions 2 units 24 (13.3%) 42 (44.7%) TOTAL % of Patients with MAE 15.0% 47.9% Difference ( ) = -32.9% p<0.001; (95% CI: -20.7%, -45.0%) 11

12 Patients Available for Analysis Through 2 Years Intention to Treat N=184 Randomized Cohort N=279 Randomized, not treated, N=6, N=15 N=3 Withdrew/Missing N=6 N=95 1 Year Analysis N=181 98% 1 Year Analysis N=89 94% N=9 Withdrew/Missing N=6 2 Year Analysis N=172 93% 2 Year Accountability 91% 2 Year Analysis N=83 87% 12

13 Device Performance Through 2 Years Intention to Treat No percutaneous device embolization No percutaneous device fracture, erosion or migration No additional occurrence of single leaflet device attachment between 1 and 2 years 1 year single leaflet device attachment rate = 6.3% 80% observed within 30 days of percutaneous procedure 100% underwent mitral valve surgery 13

14 Primary Effectiveness Endpoint Effectiveness defined as freedom from death, MV surgery/re-operation or 3+ or 4+ MR Two analyses performed: 1. Intention to Treat - Any mitral valve surgery following percutaneous repair was considered an endpoint event 2. Comparison of Treatment Strategies - Mitral valve surgery following unsuccessful in-hospital percutaneous repair is not considered an endpoint event 14

15 Primary Effectiveness Endpoint Effectiveness defined as freedom from death, MV surgery/re-operation or 3+ or 4+ MR 1. Intention to Treat Analysis - Any mitral valve surgery following percutaneous repair was considered an endpoint event 2. Comparison of Treatment Strategies - Mitral valve surgery following unsuccessful in-hospital percutaneous repair not considered an endpoint event 15

16 Primary Effectiveness Analyses at 1 and 2 Years Intention to Treat Analysis Primary Effectiveness: Freedom from death, MV surgery/re-operation or 3+ or 4+ MR Percent (%) 1 Year N=181 2 Years N=172 1 Year N=89 2 Years N=83 Randomized not treated patients assigned MR 3+ or 4+ at 1 and 2 years ( N=6, N=15) 16

17 Primary Effectiveness Analyses at 1 and 2 Years Difference Between & Intention to Treat Analysis Primary Effectiveness: Freedom from death, MV surgery/re-operation or 3+ or 4+ MR Difference: (%, 95% CI) 1 Year -30.3% -17.8% -5.2% p= Years -28.0% -14.5% -1.0% p=0.04 Favors Favors 17

18 Freedom From Death, / Re-operation for Valve Dysfunction or 3+ or 4+ MR Intention to Treat Analysis Components of Failure Death P-value 1 Year N= (6.1%) 2 Years N= (11.0%) 1 Year N=89 5 (5.6%) 2 Years N=83 9 (10.8%) vs at 2 years >0.999 MV / Re-operation 37 (20.4%) 38 (22.1%) 2 (2.2%) 3 (3.6%) < or 4+ MR 38 (21.0%) 34 (19.8%) 18 (20.2%) 18 (21.7%) 0.84 Freedom from death, MV surgery / re-operation or 3+ or 4+ MR 100 (55.2%) 89 (51.7%) 65 (73.0%) 55 (66.3%) <0.001 Randomized not treated patients assigned MR 3+ or 4+ at 1 and 2 years ( N=6, N=15) Component rates do not sum to rate of composite due to the possibility of more than one event per patient 18

19 Primary Effectiveness Endpoint Effectiveness defined as freedom from death, MV surgery/re-operation or 3+ or 4+ MR 1. Intention to Treat Analysis - Any mitral valve surgery following percutaneous repair was considered an endpoint event 2. Comparison of Treatment Strategies - Mitral valve surgery following unsuccessful in-hospital percutaneous repair not considered an endpoint event 19

20 Primary Effectiveness Analyses at 1 and 2 Years Comparison of Treatment Strategy Analysis Primary Effectiveness: Freedom from death, MV surgery/re-operation or 3+ or 4+ MR Percent (%) 1 Year N=175 2 Years N=161 1 Year N=89 2 Years N=83 Randomized not treated patients assigned MR 3+ or 4+ at 1 and 2 years ( N=6, N=15) 20

21 Primary Effectiveness Analyses at 1 and 2 Years Difference Between & Comparison of Treatment Strategies Analysis Primary Effectiveness: Freedom from death, MV surgery/re-operation or 3+ or 4+ MR Difference: (%, 95% CI) 1 Year -18.0% -5.6% 6.8% p= Years -17.1% -3.5% 10.0% p=0.67 Favors Favors 21

22 Freedom From Death, / Re-operation for Valve Dysfunction or 3+ or 4+ MR Comparison of Treatment Strategies Analysis Components of Failure P-value 1 Year N=175 2 Years N=161 1 Year N=89 2 Years N=83 vs at 2 years Death 11 (6.3%) 19 (11.8%) 5 (5.6%) 8 (9.6%) 0.67 MV / Re-operation 9 (5.1%) 10 (6.2%) 2 (2.2%) 3 (3.6%) or 4+ MR 38 (21.7%) 31 (19.3%) 18 (20.2%) 17 (20.5%) 0.87 Freedom from death, MV surgery / re-operation or 3+ or 4+ MR 118 (67.4%) 101 (62.7%) 65 (73.0%) 66 (66.3%) 0.67 Randomized not treated patients assigned MR 3+ or 4+ at 1 and 2 years ( N=6, N=15) Component rates do not sum to rate of composite due to the possibility of more than one event per patient 22

23 Kaplan-Meier Freedom from Death Intention to Treat = 95.0% = 94.9% p=0.95 = 91.1% = 89.8% p=0.78 At Risk: 0 Days 6m 1yr 1.5yr 2yr 3yr

24 Kaplan-Meier Freedom from MV (Device) or Re-operation () Intention to Treat = 97.5% = 78.8% p<0.001 = 96.1% = 78.2% p< % of Device patients are free from MV surgery at 2 years At Risk: 0 Days 6m 1yr 1.5yr 2yr 3yr

25 Landmark Analysis of Kaplan-Meier Freedom from MV ()/Re-operation () Intention to Treat = 98.7% = 96.3% p=0.32 = 97.3% = 95.6% p=0.52 At Risk: 0 Days m 1yr 1.5yr 2yr 3yr

26 Clinical Outcome Variables Intention to Treat Randomized Cohort N=279 N=184 Intention to Treat N=95 Clinical outcome measures at 2 years include: Mitral regurgitation grade Left ventricular volumes NYHA Functional Class 26

27 Mitral Regurgitation Grade Baseline, 1 and 2 Years (matched) Intention to Treat Within group difference (p<0.05) (N=122) (N=122) (N=122) (N=56) (N=56) (N=56) 27

28 Mitral Regurgitation Grade Baseline, 1 and 2 Years (matched) Intention to Treat Within group difference (p<0.05) Between group difference at 1 year (p<0.05) Between group difference at 2 year (p<0.05) (N=122) (N=122) (N=122) (N=56) (N=56) (N=56) 28

29 Within group difference (p<0.05) LV Volumes Baseline, 1 and 2 Years (matched) Intention to Treat LV End Diastolic Volume LV End Systolic Volume BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs N=117 N=55 BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs N=117 N=55 29

30 Within group difference (p<0.05) Between group difference at 1 year (p<0.05) Between group difference at 2 year (p<0.05) LV Volumes Baseline, 1 and 2 Years (matched) Intention to Treat LV End Diastolic Volume LV End Systolic Volume BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs N=117 N=55 BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs N=117 N=55 30

31 NYHA Functional Class At Baseline, 1 and 2 Years (matched) Within group difference (p<0.05) Intention to Treat I II I I I I I Percent (%) III II II II III II II IV IV III III (N=127) (N=127) (N=127) (N=56) (N=56) (N=56) 31

32 NYHA Functional Class At Baseline, 1 and 2 Years (matched) Within group difference (p<0.05) Between group difference at 1 year (p<0.05) Between group difference at 2 year (p<0.05) I I I II Percent (%) III II Intention to Treat II I I I II III II II IV IV III III (N=127) (N=127) (N=127) (N=56) (N=56) (N=56) 32

33 Summary EVEREST II RCT When percutaneous repair is compared to surgery repair provides increased safety provides more complete MR reduction 78% of percutaneous patients are free from surgery at 2 years Both percutaneous and surgical treatment reduced MR and demonstrated meaningful clinical benefits through 2 years Significantly improved LV volumes and NYHA Functional Class No loss of device integrity through 2 years Follow-up is ongoing 33

34 Conclusion EVEREST II RCT The MitraClip procedure is a therapeutic option for select patients with significant mitral regurgitation Favorable safety profile Measurable clinical benefits Improved LV volumes and NYHA Class Results are durable through 2 years 34

35 35