Establishing a New Path Forward for Patients With Severe Symptomatic Aortic Stenosis THE PARTNER TRIAL CLINICAL RESULTS E D W A R D S T R A N S C A T H E T E R H E A R T V A L V E P R O G R A M
T h e Pa r t n e r T R I A L Definitive Results Through Rigorous Design Survival rates after the onset of symptoms in severe aortic stenosis are dismal, as low as 5% at 2 years and % at 5 years. 1 Surgical aortic valve replacement () is the current standard of care, but it has been estimated that between 3% and 6% of patients do not undergo. 2,3 The PARTNER Trial (Placement of AoRtic TraNscathetER Valves) was initiated to investigate the safety and effectiveness of a less invasive treatment in this population. The world s first prospective, randomized, and controlled trial for transcatheter aortic valve implantation (TAVI), 4 The PARTNER Trial sets the standard in site selection, case screening, study management, multidisciplinary teamwork, and patient follow-up. Methodology required top-performing surgical capability in order to set the highest possible standard for comparison to TAVI. The PARTNER Trial consists of two individually powered patient cohorts. In Cohort A, the safety and effectiveness of the balloon-expandable Edwards SAPIEN Transcatheter Heart Valve (THV) was compared to in high-risk patients with severe symptomatic aortic stenosis. 4 In Cohort B, the safety and effectiveness of the balloon-expandable Edwards SAPIEN THV was compared to standard therapy (best medical management) in inoperable patients with severe symptomatic aortic stenosis. 5 EDWARDS SAPIEN TRANSCATHETER HEART VALVE
ESTABLISHING A new path forward FOR PATIENTS WITH severe symptomatic aortic stenosis THE PARTNE R Trial Protocol4 Severe Symptomatic Aortic Stenosis ASSESSMENT Operability Yes 2 Cohorts Cohort A ASSESSMENT Transfemoral Access No (n = 7) 1:1 Randomization 1:1 Randomization VS (Control) (n = 244) n = 358 ASSESSMENT Transfemoral Access Yes TA TF (n = 492) TF TAVI Cohort B Individually Powered (N = 1,57) n = 699 Yes No (n = 248) TA TAVI Not in Study 1:1 Randomization TF TAVI VS (Control) (n = 14) No (n = 13) VS Standard Therapy (n = 179) (Control) (n = 179) Cohort A inclusion criteria4-6 Cohort B inclusion criteria5 STS score STS score and/or Predicted operative mortality NYHA functional class AVA or Mean AVG or Peak jet velocity 1 15% II <.8 cm2 > 4 mm Hg > 4. m/s Predicted operative mortality NYHA functional class AVA or Mean AVG or Peak jet velocity 11.6* > 5% II <.8 cm2 > 4 mm Hg > 4. m/s *This mean score reflects enrolled patient group; not required for inclusion. Patient selection required at least two cardiothoracic surgeons and an interventional cardiologist to agree that patients were not suitable candidates for surgery.4,5 AVA, aortic valve area; AVG, aortic valve gradient; NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; TA, transapical; TF, transfemoral.
Cohort A T h e Pa r t n e r T R I A L Survival With Edwards SAPIEN THV Was Equivalent to in High-Risk Patients PRIMARY ENDPOINT: ALL-CAUSE MORTALITY AT 1 YEAR (ITT) 4 5 Edwards THV P (log rank) =.62 4 All-Cause Mortality, % 3 26.8% 24.2% 1 No. at Risk 6 12 18 24 Months Edwards THV 348 298 26 147 67 351 252 236 139 65 Mortality at 1 year Edwards SAPIEN THV 24.2% 26.8% (P =.1 for non-inferiority) 4 Results for both procedures exceeded ExPECTATIONS *4,6 Expected 3-day mortality rate: 11.8% Observed 3-day mortality rate: 8.% O:E ratio =.68 Edwards SAPIEN THV Expected 3-day mortality rate: 11.7% Observed 3-day mortality rate: 5.2% O:E ratio =.44 * As-treated (AT) analysis. ITT, intent to treat.
ESTABLISHING A NEW PATH FORWARD FOR PATIENTS WITH SEVERE SyMPTOMATIC AORTIC STENOSIS Transfemoral Approach Equivalent to ALL-CAUSE MORTALITY: TRANSFEMORAL (ITT, N = 492) 4 Transfemoral TAVI subgroup non-inferior to (P =.2) 4 All-Cause Mortality, % 5 4 3 1 Edwards THV 26.4% P (log rank) =.25 22.2% No. at Risk 6 12 18 24 Months Edwards THV 244 215 188 119 59 248 18 168 19 56 Transapical Approach Results ALL-CAUSE MORTALITY: TRANSAPICAL (ITT, N = 7) 4 While not powered for independent statistical analysis, the transapical TAVI subgroup showed similar results as at 1 year 4 All-Cause Mortality, % No. at Risk 5 4 3 1 Edwards THV 29.% P (log rank) =.41 27.9% 6 12 18 24 Months Edwards THV 14 83 72 28 8 13 72 68 3 9
Cohort A T h e Pa r t n e r T R I A L Clinical Outcomes: High-Risk Patients Both TAVI and were associated with important but different periprocedural hazards. 3 Days 4 1 Year 4 Outcome Edwards SAPIEN THV (n = 348) (n = 351) P Value Edwards SAPIEN THV (n = 348) (n = 358) P Value All-Cause Mortality 3.4% 6.5%.7 24.2% 26.8%.44 All Stroke or TIA 5.5% 2.4%.4 8.3% 4.3%.4 Major Stroke 3.8% 2.1%. 5.1% 2.4%.7 Major Vascular Complications 11.% 3.2% <.1 11.3% 3.5% <.1 Major Bleeding 9.3% 19.5% <.1 14.7% 25.7% <.1 New Atrial Fibrillation 8.6% 16.% <.1 12.1% 17.1% <.7 New Pacemaker 3.8% 3.6%.89 5.7% 5.%.68 TIA, transient ischemic attack. Edwards SAPIEN THV: Statistically higher incidence of all stroke or TIA and major vascular complications 4 : Statistically higher incidence of major bleeding and new atrial fibrillation 4
ESTABLISHING A NEW PATH FORWARD FOR PATIENTS WITH SEVERE SyMPTOMATIC AORTIC STENOSIS and Edwards SAPIEN THV Improved Hemodynamics and Sustained Valve Performance ECHO FINDINGS: AORTIC VALVE GRADIENTS 4 Mean and Peak Gradient As-Treated Trial Arms (mm Hg) 8 7 6 5 4 3 1 Peak Gradient Peak Gradient TAVI Mean Gradient Mean Gradient TAVI Baseline 3 Days 1 Year Edwards THV n = 327 n = 287 n = 227 n = 31 n = 231 n = 159 23 mm 15 mm Carpentier Edwards PERIMOUNT Magna Ease Heart Valve 23 mm 14.3 mm Edwards sapien Transcatheter Heart Valve Consistent hemodynamics and valve performance between Edwards SAPIEN THV and Edwards Magna Ease* 4 Edwards SAPIEN THV Rapidly Improved Symptoms, With Results Equivalent to at 1 Year NYHA FUNCTIONAL CLASS 4 Patients Surviving, % 1 8 6 4 P = 1. P <.1 P =.75 I II III IV 85% of patients in NYHA class I or II at 1 year 4 TAVI TAVI TAVI Baseline 3 Days 1 year Symptom improvement favored Edwards SAPIEN THV at 3 days and was similar to that with at 1 year 4 *A range of surgical valve sizes were used in the arm and both the 23 mm and the 26 mm SAPIEN valves were used in the TAVI arm. Edwards surgical valves were used in 9% of patients in the arm. 6
Cohort B T h e Pa r t n e r T R I A L Edwards SAPIEN THV Significantly Improved Survival in Inoperable Patients Co-Primary ENDPOINT: All-CAUSE MORTALITy 4,5 All-Cause Mortality, % 1 8 6 4 P <.1 at 1 y =.% NNT = 5. pts 5.7% Standard Therapy Edwards THV 3.7% 6 12 18 24 Months % absolute reduction in mortality 5 Despite expert care and frequent BAV (78.2%), standard therapy failed to alter the dismal natural course of disease 5,6 24% absolute reduction in cardiovascular mortality at 1 year (P <.1) 4,6 29% absolute reduction in all-cause mortality or repeat hospitalization at 1 year (co-primary endpoint; P <.1) 4,6 NNT = 5 Need to treat just 5 patients with an Edwards SAPIEN THV to save a life 4
ESTABLISHING A NEW PATH FORWARD FOR PATIENTS WITH SEVERE SyMPTOMATIC AORTIC STENOSIS Edwards SAPIEN THV Significantly Improved Symptoms and Quality of Life* NYHA Class OVER Time 4,5 75% of the Edwards SAPIEN THV patients in NYHA class I or II at 1 year 5 Patients, % 1 8 6 4 P =.68 P <.1 I II III IV Edwards Standard Edwards Standard THV Therapy THV Therapy Baseline 1 Year Significant improvement observed as early as 3 days (P <.1) 5 KCCQ scores over time 4 25-point treatment effect in KCCQ score 6 KCCQ Score 7 6 5 4 3 1 MCID = 5 pts = 13.9 P <.1 =.7 P <.1 = 24.5 P <.1 Edwards THV Standard Therapy 2 4 6 8 1 12 Months -point improvement in KCCQ score represents change of large clinical importance 7 *NYHA and KCCQ scores of surviving patients only. BAV, balloon aortic valvuloplasty; KCCQ, Kansas City Cardiomyopathy Questionnaire; MCID, minimum clinically important difference.
T h e P a r t n e r T R I A L The PARTNER Trial: Critical Insights Extraordinary news for patients Both TAVI with Edwards SAPIEN THV delivered transfemorally and transapically and offer meaningful, life-changing benefits for patients with severe symptomatic aortic stenosis who are in critical need TAVI with Edwards SAPIEN THV is the new standard of care for patients with inoperable severe symptomatic aortic stenosis 5 NNT = 5 Need to treat just 5 patients to save a life 4 Both treatments have considerations TAVI and were associated with important but different periprocedural hazards that merit consideration by clinicians Edwards SAPIEN THV Statistically higher incidence of all stroke and TIA and major vascular complications 4,5 Surgical Statistically higher incidence of major bleeding and new atrial fibrillation 4 It takes a team The multidisciplinary heart team with interventional cardiologists and cardiothoracic surgeons leading the way leverages The PARTNER Trial approach for remarkable patient outcomes
ESTABLISHING A NEW PATH FORWARD FOR PATIENTS WITH SEVERE SyMPTOMATIC AORTIC STENOSIS The PARTNER Trial: Investigator Interpretations On the basis of a rate of death from any cause at 1 year that was percentage points lower with TAVI than with standard therapy, balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery. The Partner Trial Investigators. TRANSCATHETER aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. Oct 1 5 This is the ideal opportunity, because surgical is one of the most effective operations surgeons offer, and T is the most exciting new treatment for aortic stenosis in the past two to three decades. This opens up a new set of patients who may very well benefit as much by T as by the conventional gold standard surgery. Craig R. Smith, MD, Chief, Division of Cardiothoracic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, and the Co-principal Investigator of The PARTNER Trial 6 These extraordinary results are accomplished because of an unprecedented teamwork between a cardiologist, cardiac surgeon, and the associated caregivers. E. Murat Tuzcu, MD, Vice Chairman, Department of Cardiology in the Sydell and Arnold Heart & Vascular Institute, Cleveland Clinic, and Investigator, The PARTNER Trial 6 T, transcatheter aortic valve replacement.
Appropriate Patients With Severe Symptomatic Aortic Stenosis Benefit With All Methods of Valve Delivery Both TAVI, delivered transfemorally or transapically, and showed reduced mortality, improved hemodynamics, and improvement of symptoms in high-risk patients Outcomes were better than expected for all three treatment groups TAVI reduced mortality, improved hemodynamics, and remarkably improved symptoms in inoperable patients References 1. Otto CM. Timing of aortic valve surgery. Heart. ;84:211-218. 2. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J. 3;24:1231-1243. 3. Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis. 6;15:312-321. 4. Smith, CR. Transcatheter vs surgical aortic valve replacement in high risk patients with severe aortic stenosis: results from The PARTNER Trial. Presented at: 11 American College of Cardiology Annual Scientific Session; April 2, 11; New Orleans, LA. 5. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 1;363;1597-167. 6. Data on file, Edwards Lifesciences. 7. KCCQ interpretability. Cardiovascular Outcomes Inc. http://cvoutcomes.org/pages/3217. Accessed May 3, 11. The Edwards SAPIEN transcatheter heart valve and delivery systems bearing the CE conformity marking comply with the requirements of the European Medical Device Directive 93/42/EEC. For professional use. See instructions for use for full prescribing information, including indications, contraindications, warnings, precautions, and adverse events. Caution: Not intended for US distribution. Edwards, Edwards Lifesciences, the stylized E logo, Carpentier-Edwards, Edwards SAPIEN, Magna Ease, PARTNER, and PERIMOUNT are trademarks of Edwards Lifesciences Corporation. 11 Edwards Lifesciences Corporation. All rights reserved. E28/4-11/THV Edwards Lifesciences Irvine, USA I Nyon, Switzerland I Tokyo, Japan I Singapore, Singapore I São Paulo, Brazil edwards.com