TAVR 肾动脉去交感神经治疗顽固性高血压 对第三代 DES 的评价 新的药物

Transcription

1 ACC 2012 亮点

2 TAVR 肾动脉去交感神经治疗顽固性高血压 对第三代 DES 的评价 新的药物

3 TAVR 肾动脉去交感神经治疗顽固性高血压 对第三代 DES 的评价 新的药物

4 Axel Linke University of Leipzig Heart Center, Leipzig, Germany Ulrich Gerckens Gemeinschaftskrankenhaus Bonn, Bonn, Germany Peter Wenaweser University Hospital Bern, Bern, Switzerland Corrado Tamburino Ferrarotto Hospital, University of Catania, Catania, Italy Johan Bosmans University Hospital Antwerp, Antwerp Belgium Stephen Brecker St. George s Hospital, London, United Kingdom Robert Bauernschmitt ISAR Heart Center, Munich, Germany (on behalf of the ADVANCE Investigators)

5 CoreValve ADVANCE Background Medtronic CoreValve System Porcine pericardial tissue valve sutured into a self expanding nitinol frame Supra-annular valve position preserves circularity at level of valve function 18Fr catheter delivery system 3 valve sizes

6 CoreValve ADVANCE Methods 1,015 patients enrolled from March 2010 to July year follow-up 44 centers - 12 countries in Western Europe, Asia and South America All centers had conducted at least 40 TAVI procedures prior to the study and had Heart Team in place Clinical endpoints reported according to Valve Academic Research Consortium (VARC)

7 CoreValve ADVANCE Baseline Characteristics

8 CoreValve ADVANCE Procedural Results

9 CoreValve ADVANCE Valve Performance

10 CoreValve ADVANCE Symptom Status

11 CoreValve ADVANCE 30-day Outcomes

12 CoreValve ADVANCE 6-month Survival

13 TAVR 肾动脉去交感神经治疗顽固性高血压 对第三代 DES 的评价 新的药物

14 Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 03/12 Effects of Increased Sympathetic Tone Causes of increased afferent signaling from the kidney to central integrative structures Consequences of increased efferent sympathetic outflow to the kidney and other organs Factors that might contribute to increased renal afferent signaling: Adenosine Acidosis Oxidative stress Inflammation Endothelial factors Angiotensin II ischemia - Renal denervation - Remodeling Hypertrophy Arrhythmias Ischemia Apoptosis Medial hyperplasia Arterial compliance Endothelial dysfunction Renal injury / Renal ischemia Na + / H 2 O retention Reduced renal blood flow Activation of the RAAS Proteinuria Glomerulosclerosis

15 Catheter-Based Radiofrequency Renal Nerve Ablation Standard interventional technique 4-6 two-minute treatments per artery Proprietary RF Generator Automated Low-power Built-in safety algorithms Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. 15

16 Symplicity HTN-1: Long-term follow-up of catheter-based renal sympathetic denervation for resistant hypertension confirms durable blood pressure reduction Paul A. Sobotka, MD, FACP, FACC Professor of Medicine/Cardiology The Ohio State University, Columbis, OH Medical Advisor, Medtronic, Inc. Santa Rosa, CA Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved.

17 Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 03/12 Baseline Patient Characteristics (n=153) Demographics Age (years) 57 ± 11 Gender (% female) 39% Race (% non-caucasian) 5% Co-morbidities Diabetes Mellitus II (%) 31% CAD (%) 22% Hyperlipidemia (%) 68% egfr (ml/min/1.73m 2 ) 83 ± 20 Blood Pressure Baseline BP (mmhg) 175/98 ± 17/15 Number of anti-htn meds (mean) 5.1 ± 1.4 Diuretic (%) 95% Aldosterone blocker(%) 22% ACE/ARB (%) 91% Direct Renin Inhibitor 14% Beta-blocker (%) 82% Calcium channel blocker (%) 75% Centrally acting sympatholytic (%) 33% Vasodilator (%) 19% Alpha-1 blocker 19% Symplicity HTN-1 Investigators. Hypertension. 2011;57:

18 Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 03/12 Procedure Detail & Safety 38 minute median procedure time Average of 4 ablations per artery Intravenous narcotics & sedatives used to manage pain during delivery of RF energy No catheter or generator malfunctions No major complications Minor complications 4/153: 1 renal artery dissection during catheter delivery (prior to RF energy), no sequelae 3 access site complications, treated without further sequelae Symplicity HTN-1 Investigators. Hypertension. 2011;57:

19 Change in Office Blood Pressure Through 36 Months BP change (mmhg) P<0.01 for from BL for all time points Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 03/2012

20 Change in Office Blood Pressure for 24 Patients with 36 Month Follow-up BP change (mmhg) P<0.01 for from BL for all time points Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 03/2012

21 egfr (ml/min/1.73m 2 ) Renal Function Over Time Caution: The Symplicity Catheter System is an Investigational Device. Limited by U.S. law to investigational use. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 03/2012

22 Renal Sympathetic Denervation for Treatment of Resistant Hypertension: One- Year Results from the Symplicity HTN-2 Randomized Controlled Trial Prof Murray Esler Baker IDI Heart and Diabetes Institute, Melbourne On behalf of Henry Krum, Markus Schlaich, Roland Schmieder, Michael Böhm, Paul Sobotka and the Symplicity HTN-2 Investigators

23 Patient Disposition Assessed for Eligibility (n=190) Screening Excluded During Screening, Prior to Randomization (n=84) BP < 160 at Baseline Visit (after 2-weeks of medication compliance confirmation) (n=36; 19%) Ineligible anatomy (n=30; 16%) Declined participation (n=10; 5%) Other exclusion criteria (n=8; 4%) Randomized (n=106) Allocation Allocated to Renal Denervation (n=52) Allocated to Control (n = 54) Follow-up No Six-Month Primary Endpoint Visit (n = 3) Reasons: Withdrew consent (n=1) Missed visit (n=2) No Six-Month Primary Endpoint Visit (n = 3) Reasons: Withdrew consent (n=2) Lost to follow-up (n=1) Analysis Analyzed (n = 49) Analyzed (n = 51)

24 Primary Endpoint: 6-Month Office BP from Baseline to 6 Months (mmhg) RDN (n=49) Systolic Diastolic Control (n=51) 1 Systolic 33/11 mmhg difference between RDN and Control (p<0.0001) 0 Diastolic Symplicity HTN-2 Investigators. Lancet. 2010;376:

25 Patient Disposition Assessed for Eligibility (n=190) Screening Randomized (n=106) Excluded During Screening, Prior to Randomization (n=84) BP < 160 at Baseline Visit (after 2-weeks of medication compliance confirmation) (n=36; 19%) Ineligible anatomy (n=30; 16%) Declined participation (n=10; 5%) Other exclusion criteria discovered after consent (n=8; 4%) 6-month Primary End-Point Allocated to RDN N=52 Treated N=49 Analyzable Allocated to Control N=54 Control N=51 Analyzable Crossover N=46 (2 LTFU) 12-month Post- Randomization 12-month post-rdn N=47 Per protocol, 6-mo Post RDN (Crossover) N=35 Not-per-protocol*, 6-mo Post RDN (Crossover) N=9 * Crossed-over with ineligible BP (<160 mmhg)

26 Change in Office Blood Pressure (mm Hg) mo post randomization 6-mo post-rdn* 6-mo Crossover 12- mo post randomization 12-mo post-rdn* Crossover 6-mo post-rdn* RDN SBP RDN DBP Cross over SBP Cross over DBP * P<0.001 for SBP and DBP change from baseline P=0.026 for SBP change from baseline

27 Other Safety 6 to 12 Months Post Randomization Three hypertensive events occurred in 2 patients in the crossover group requiring hospitalization No deaths occurred at any time point during the follow up period for either group No observed changes in egfr

28 TAVR 肾动脉去交感神经治疗顽固性高血压 对第三代 DES 的评价 新的药物

29 Zotarolimus Release (%) System Components Established Components Integrity cobalt alloy stent Resolute Integrity DES Unique Polymer Technology BioLinx polymer is a unique blend of three polymers to control drug release, support biocompatibility and enhance elution rate MicroTrac delivery system Drug-release kinetics: complete elution by 180 days Zotarolimus antiproliferative drug Udipi K, et al. EuroIntervention. 2007; 3:137-9 Meredith IT, et al. J Am Coll Cardiol Intv. 2009; 2: Meredith IT, et al. EuroIntervention. 2007; 3: % eluted Days

30 Pooled Analysis of Clinical Events From Prospective Trials of the Resolute Zotarolimus-eluting Stent: Two Year Outcomes of 5130 Patients J. Belardi, MD, FACC On Behalf of A. Yeung, M. Leon, P. Serruys, I. Meredith, S. Windecker, S. Silber, F-J. Neumann, P. Widimský, S. Saito, J. Massaro, L. Mauri and the RESOLUTE Clinical Program Investigators ACC 2012

31 RESOLUTE Global Clinical Program 5130 Patients in Pooled Analysis Enrollment Complete - In Follow Up RESOLUTE 1 Non-RCT First-in-Human (R=139) 5 yr RESOLUTE AC 2,3 1:1 RCT vs. Xience V (R=1140; X=1152) 2 yr RESOLUTE Int 4 Non-RCT Observational (R=2349) 2 yr RESOLUTE US mm Non-RCT vs. Hx Control (R=1402) 2 yr RESOLUTE Japan mm Non-RCT (R=100) vs. Hx Control 2 yr R Japan SVS RESOLUTE US 2.25 Non-RCT vs. PG (R=65) < 1yr 38 mm sub-study Non-RCT vs. PG (R=114) < 1yr R-China RCT RESOLUTE Asia R-China Registry 1:1 RCT vs. Taxus (R=200; T=200) Non-RCT Observational (R=312) Non-RCT Observational (R=1800) < 1yr < 1yr < 1yr Enrolling / Planning RI-US Registry Post-approval study (R=230) 1 Meredith IT, et al. EuroIntervention. 2010;5: Serruys PW, et al. N Engl J Med. 2010;363: Silber S, et al. Lancet. 2011;377: Neumann FJ, et al. EuroIntervention. 2012;7(10): Yeung AC, et al. JACC. 2011;57: plan

32 RESOLUTE Pooled Baseline and Lesion Characteristics R-ZES Pooled 1 N = 5130 Age (years, mean ± SD) 63.8 ± 11.0 Females (%) 25.1 Prior MI (%) 26.4 Diabetics (%) 29.9 Unstable angina (%) 25.9 RVD (mm) 2.85 ± 0.51 Lesion length (mm) ± 9.91 B2/C lesions (%) 71.1 Complex patients 2 (%) RESOLUTE(5yr), R-AC (2yr), R-Int (2yr), R-US (2yr), R-Japan (2yr) 2 Complex patient definition: bifurcation, bypass grafts, ISR, AMI <72 hr, LVEF <30%, unprotected LM, >2 vessels stented, renal insufficiency or failure (creatinine >140 µmol/l), lesion length >27 mm, >1 lesion per vessel, lesion with thrombus or TO (preprocedure TIMI = 0). Only R-AC and R-INT included complex patients.

33 Event Rates (%) RESOLUTE Pooled TLF and Components at 2 Years Resolute ZES Pooled (n = 5014) TLF Cardiac TVMI QMI NQMI TLR Death TLF (Target Lesion Failure) is defined as Cardiac Death, TVMI, or clinically indicated TLR.

34 RESOLUTE Pooled Stent Thrombosis ARC Definite/Probable to 2 Years Cumulative Incidence of ARC Def/Prob ST 10% Resolute ZES Pooled (N = 5130) 8% 6% 4% 2% 0% Time After Initial Procedure (months) No. at risk R-ZES % CI

35 Cumulative Incidence of TLF Cumulative Incidence of TLR RESOLUTE Pooled Perspective: Comparison to Xience V EES in R-AC Cumulative Incidence of Cardiac Death/TVMI Cumulative Incidence of ARC Def/Prob ST Resolute ZES Pooled* (N = 5130) Xience V EES (R-AC, N = 1152) Target Lesion Failure Cardiac Death/Target Vessel MI 20% 10% 15% 8% % % 9.3 4% 5% 6.6 2% % Time After Initial Procedure (months) 0% Time After Initial Procedure (months) 10% 8% Target Lesion Revascularization 10% 8% Stent Thrombosis (ARC Definite/Probable) 6% % 2% 3.3 0% Time After Initial Procedure (months) 6% 4% 0.8 2% % Time After Initial Procedure (months) *Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US, R-Japan

36 Two-Year Outcomes of Patients Treated with the Resolute Zotarolimus-Eluting Stent in Different Indications: ST Elevation Myocardial Infarction versus Acute Coronary Syndrome Without ST Segment Elevation versus Stable Angina: A Pooled Analysis from the RESOLUTE Clinical Program P. Widimský, On behalf of J. Belardi, M. Leon, L. Mauri, I. Meredith, F-J. Neumann, S. Saito, P. Serruys, S. Silber, S. Windecker, A. Yeung and the RESOLUTE Clinical Program Investigators ACC 2012

37 Event Rates (%) RESOLUTE Pooled STEMI, Non-STEACS, Stable Angina Outcomes at 2 Years STEMI Non-STEACS Stable angina Cardiac Death TV-MI TLR ST ARC Def/Prob TLR is ischemia driven.

38 The Resolute Zotarolimus-eluting Stent in Patients with Diabetes Mellitus: Two Year Outcomes Alan C. Yeung, MD Stanford University School of Medicine, Palo Alto, CA On behalf of M. Leon, S. Silber, P. Serruys, S. Windecker, J. Belardi, I. Meredith, F-J. Neumann, P. Widimsky, S. Saito, J. Massaro, L. Mauri and the RESOLUTE Clinical Program Investigators ACC 2012

39 Cumulative Incidence of Cardiac Death/TLR RESOLUTE Pooled Diabetic Analysis Standard Risk Pts Target Lesion Revascularization to 2 Years 20% 15% Non-Diabetics (N = 1903) Non-IDDM (N = 628) IDDM (N = 250) 10% 5% 5.4% 2.6% 6.5% 4.3% 3.4% 0% 0 2.1% Time After Initial Procedure (months) No. at risk Non-Diabetics Non-IDDM IDDM Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

40 Cumulative Incidence of Cardiac Death/TVMI RESOLUTE Pooled Diabetic Analysis Standard Risk Pts Cardiac Death/TVMI to 2 Years 20% 15% Non-Diabetics (N = 1903) Non-IDDM (N = 628) IDDM (N = 250) 10% 5% 0% 0 8.6% 6.0% 3.1% 4.1% 3.9% 2.6% Time After Initial Procedure (months) No. at risk Non-Diabetics Non-IDDM IDDM Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

41 Cumulative Incidence of ARC Def/Prob ST RESOLUTE Pooled Diabetic Analysis Standard Risk Pts ARC Def/Prob Stent Thrombosis to 2 Years 10% 8% Non-Diabetics (N = 1903) Non-IDDM (N = 628) IDDM (N = 250) 6% 4% 2% 0% % 0.32% 0.16% 0.80% 0.43% 0.16% Time After Initial Procedure (months) No. at risk Non-Diabetics Non-IDDM IDDM Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

42 A New Strategy for Discontinuation of Dual Antiplatelet Therapy: Real Safety and Efficacy of 3-Month Dual Antiplatelet Therapy Following Zotarolimus-Eluting Stent Implantation: RESET Trial Myeong-Ki Hong, MD. Ph D, on behalf of RESET investigators Professor, Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Medicine, Seoul, Korea RESET ClinicalTrials.gov identifier: NCT

43 Study at a glance & Final Enrollment 2,148 patients enrolled and randomized E-ZES + 3-month DAPT Standard Therapy: Other DES with 12-month DAPT Divided into 4 subsets and 1:1 randomization was performed. 31 patients excluded - 16 Withdrawal of consent - 15 Met exclusion criteria E-ZES + 3-month DAPT (n=1059) Standard therapy (n=1058) Diabetes mellitus subset (N=292) Acute coronary syndrome subset (N=601) Short-length DES Subset (N=681) Long-length DES Subset (N=543) E-ZES (n=146) R-ZES (n=146) E-ZES (n=301) R-ZES (n=300) E-ZES (n=341) SES (n=340) E-ZES (n=271) EES (n=272) R-ZES = Resolute zotarolimus-eluting stent ; SES = sirolimus-eluting stent; EES = everolimus-eluting stents

44 Cumulative event rate (%) Cumulative incidence (%) Primary endpoint, by Kaplan-Meier method Primary endpoint * Primary end-point; A composite of death from CV cause, MI, stent thrombosis, TVR or bleeding at 1 year Difference = 0.0% 95% CI, -2.5 to 2.5; p = 0.84 Standard therapy E-ZES + 3-month DAPT p-value for non-inferiority < % 4.7% No. at Risk E-ZES +3-month DAPT Months after 1037 the index procedure Standard therapy Months

45 Cumulative event incidence rate (%) (%) Any death, MI, or stent thrombosis 8 Death from any cause, myocardial infarction, or stent thrombosis Standard therapy E-ZES + 3-month DAPT 6 p-value by log-rank test = % 0 0.8% No. at Risk E-ZES+ 3-month DAPT Months after the index procedure Standard therapy Months

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