As Fronteiras da Cardiologia SBHCI, ABSORB BVS is neither approved nor available for sale in the U.S.

Transcrição

1 As Fronteiras da Cardiologia Intervencionista Alexandre Abizaid Instituto Dante Pazzanese de Cardiologia Sao Paulo, Brasil SBHCI, 2012 ABSORB BVS is neither approved nor available for sale in the U.S.

2 Novas Fronteiras da Cardiologia Intervencionista 1. Novas gerações de stents t farmacológicos e suporte vascular bioabsorvível 2. Denervaçāorenal 3. Tratamento percutâneo da estenose aórtica

3 Novas Fronteiras da Cardiologia Intervencionista 1. Novas gerações de stents t farmacológicos e suporte vascular bioabsorvível 2. Denervaçāorenal 3. Tratamento percutâneo da estenose aórtica

4 Biolimus-A9 Eluting Stent Biolimus is a semi-synthetic synthetic sirolimus analogue with 10x higher lipophilicity p and similar potency as sirolimus. Biolimus is immersed at a concentration of 15.6 g/mm into a biodegradable polymer, polylactic acid, and applied solely to the abluminal stent surface by a fully automated process. Biolimus is co-released with polylactic acid and completely desolves into carbon dioxide and water after a 6-9 months period. The stainless steel stent platform has a strut thickness of 120 m m with a quadrature link design.

5 LEADERS: Definite ST 1-Year Landmark Analysis SES BES 0 to 1 year RR 1 to 4 year RR 0.99 ( ) 0.20 ( ) P=0.98* P=0.004 % % 2.0% 20% 2.0% 0.4% Months after index PCI Ischinger T. TCT 2011

6 Abluminal Bioabsorbable Polymer BSC Synergy stent t Bioabsorbable polymer (PLGA) Applied only to the abluminal surface Thin strut ( ) PtCr Stent Abluminal Bioabsorbable Polymer PLGA Bioabsorbable Polymer + Everolimus on Abluminal Side of Stent Current Durable Polymer Durable Permanent Polymer + Drug 360 Around Stent

7 Cre8 TM : Distinctive Features Polymer-Free platform Avoids complications due to the presence of a polymer interface with blood flow or the vessel wall Abluminal Reservoir Technology (ART) Controlled and directed elution to the vessel wall Bio Inducer Surface (BIS) = 2 nd generation pure carbon coating Amphilimus Formulation = Formulated Sirolimus with an organic acid Optimal hemo-compatibility Enhanced drug bioavailability, permeability and maximized product overall safety and efficacy

8 DFS: Drug Filled Stent (Medtronic) Drug elution controlled by diffusion physics Elution Holes

9 Mitsu - Merilimus Eluting Coronary Stent System Unmet Clinical i l Need A low injury stent with an ability to endothelialize quickly for early discontinuation of DAPT Device Description 40 µm cobalt chromium (L605) stent Hybrid stent geometry Mounted on a newly created extra support balloon catheters for increased deliverability. Employs low dose of Merilimus, formulated within solid-lipid lipid nano particles (165 µm) Rapid penetration of Solid Lipid Nano particles into arterial layers Mabel Cobalt Chromium Coronary Stent 40 µm fkbp-12 adaptation by Merilimus molecule SEM Solid Lipid Nano Coating

10 Novas Fronteiras da Cardiologia Intervencionista 1. Novas gerações de stents t farmacológicos e suporte vascular bioabsorvível 2. Denervaçāorenal 3. Tratamento percutâneo da estenose aórtica

11 Vantagens do Suporte Vascular Bioabsorvivel Efeito eto mecânico co de um stent t metálico e subsequente absorção pelo organismo. Restaurar a resposta vascular (vasoreatividade) Reduzir estímulo para reação inflamatória crônica (menor tempo de DAPT) Facilitar revascularizações futuras. Compatibilidade com testes nao invasivos.

12 Bioresorbable Stents Igaki-Tamai BVS REVA Elixir PLA PLLA Tyrosine- Policarbonate PLLA Biotronik o Magnesium

13 Bioresorbable Stents BVS (Abbott) PLLA

14 Everolimus Eluting Bioresorbable Vascular Scaffold ML VISION Delivery System Bioresorbable bl Device Platform Bioresorbable bl Coating Everolimus Seven generations of MULTI-LINK success World-class deliverability Polylactide (PLLA) Naturally resorbed, fully metabolized Polylactide (PDLLA) coating Fully biodegradable Similar dose and release rate to XIENCE V All illustrations are artists renditions 14

15 ABSORB EXTEND Non Randomized, Randomized,Single Arm, Continued Access Trial Clinical follow-up MSCT follow-up (n=100) OCT follow-up (n=50) 1000 subjects Up to 100 International sites 30 d 6 mo 12 mo 24 mo 36 mo Study Objective: Continued Access trial. FPI * : Jan 11, 2010 Endpoints: Treatment: Device Sizes: No hypothesis-testing, typical PCI clinical endpoints Up to 2 de novo lesions in different epicardial vessels Planned overlapping allowed in lesions >22 and 28 mm Scaffold diameters: 2.5, 3.0 mm Scaffold lengths: 18, 28 mm * FPI: First Patient In ABSORB BVS is neither approved nor available for sale in the U.S.

16 6 Month Clinical Follow up (ITT Population) Registered N = = pending 30D F/U** 30 Day Followup N=451 1 = Cardiac Death 1 = Vascular Death 180 = pending 6M F/U** 6M Month thfollow- up* N=269 Covers a registration period of January 11, 2010 to January 11, 2012 *F/U window ±14 days **As of the cut-off date of Jan ABSORB BVS is neither approved nor available for sale in the U.S.

17 MACE Through 6 Months (ITT Interim Snapshot) MACE (% %) Cohort B EXTEND 194-day HR 0.62 [0.22,1.76] p=0.36 * 5.0% Δ =21% 2.1% 2.9% Number at risk Time Post Index Procedure (Months) Time after index procedure (days) Cohort B EXTEND Note: MACE is defined as the composite of cardiac death, MI, and ischemia-driven TLR * P-value is not from formal hypothesis testing and is displayed for descriptive purpose only. ABSORB BVS is neither approved nor available for sale in the U.S.

18 TVF Through 6 Months (ITT Interim Snapshot) 10 TVF (%) Cohort B EXTEND 194-day HR 0.68 [0.24,1.93] p=0.47 * 5.0% Δ = 1.7% 33% 3.3% Number at risk Time Post Index Procedure (Months) Time after index procedure (days) Cohort B EXTEND Note: TVF is defined as the composite of cardiac death, MI, ischemia-driven TLR, and ischemia-driven TVR, non-tl * P-value is not from formal hypothesis testing and is displayed for descriptive purpose only. ABSORB BVS is neither approved nor available for sale in the U.S.

19 ST (def/prob) Through 6 Months (ITT Interim Snapshot) Definite/ /Probable ST (%) Number at risk Cohort B EXTEND 194-day HR NA [NA] p=0.51 * Δ = 0.4% Time Post Index Procedure (Months) 0.4% 00% 0.0% Time after index procedure (days) Cohort B EXTEND * P-value is not from formal hypothesis testing and is displayed for descriptive purpose only. ABSORB BVS is neither approved nor available for sale in the U.S.

20 Novas Fronteiras da Cardiologia Intervencionista 1. Novas gerações de stents t farmacológicos e suporte vascular bioabsorvível 2. Denervaçāorenal 3. Tratamento percutâneo da estenose aórtica

21 Chronic Hypertension Significant Unmet Clinical Need 30% 35% Untreated 35% Treated & Controlled Treated but Uncontrolled Hypertension medications work, but not as well as you may think Astonishing prevalence: Affects 1 in 3 adults 1B people worldwide 1.6B by 2025 Single largest contributor to death Every 20 mmhg increase in systolic BP doubles 10-year cardiovascular mortality Dramatically increases risk of heart attack, stroke, heart failure, kidney failure & insulin resistance Only half of all treated hypertensives are controlled to established BP targets Physician Inertia Patient Compliance Resistant HTN Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):

22 Failure of Current Multidrug Approach to Successfully Treat Hypertension Percentage e of Patient ts (%) 53% 41% 29% 34% 50% 16% 61% Kearney PM, et al. J Hypertens. 2004; 22:11-19.

23 Renal Sympathetic Efferent Nerve Activity Kidney as Recipient of Sympathetic Signals Renal Efferent Nerves Renin Release RAAS activation Sodium Retention Renal Blood Flow 23

24 Renal Sympathetic Afferent Nerves Kidney as Origin of Central Sympathetic Drive Vasoconstriction Atherosclerosis Insulin Resistance Sleep Disturbances Renal Afferent Nerves Hypertrophy Arrhythmia Oxygen Consumption Renin Release RAAS activation Sodium Retention Renal Blood Flow 24

25 Current Approach for Renal Denervation

26 OneShot TM Catheter Irrigation holes cool non-treated endothelial surface

27 Symplicity HTN-1 Initial Cohort Reported in the Lancet, 2009: First-in-man, non-randomized Cohort of 45 patients with resistant HTN (SBP 160 mmhg on 3 anti-htn drugs, including a diuretic; egfr 45 ml/min /min) 12-month data Expanded Cohort This Report (Symplicity HTN-1): Expanded cohort of patients (n=153) 24-month follow-up Lancet ;373: Sievert et al. European Society of Cardiology

28 Significant, Sustained BP Reduction 10 0 Systolic Diastolic BP change (mmhg) M (n=138) 3 M (n=135) 6 M (n=86) 12 M (n=64) 18 M (n=36) 24 M (n=18) Sievert et al. European Society of Cardiology

29 Symplicity HTN-2 PURPOSE: To demonstrate the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with uncontrolled hypertension in a prospective, p randomized, controlled, clinical trial PATIENTS: 106 patients randomized 1:1 to treatment with renal denervation vs. control CLINICAL SITES: 24 centers in Europe, Australia, & New Zealand (67% were designated hypertension centers of excellence) Lancet ;376: Symplicity HTN-2 Investigators. Lancet ;376:

30 Primary Endpoint: 6-Month Office BP mmhg) 6 Months (m seline to 6 from Ba RDN (n=49) Control (n=51) /11 mmhg difference between RDN and Control (p<0.0001) Systolic Diastolic 84% of RDN patients had 10 mmhg reduction in SBP 10% of RDN patients had no reduction in SBP Symplicity HTN-2 Investigators. Lancet ;376:

31 Novas Fronteiras da Cardiologia Intervencionista 1. Novas gerações de stents t farmacológicos e suporte vascular bioabsorvível 2. Denervaçāorenal 3. Tratamento percutâneo da estenose aórtica

32 A Populaçã ção potencial de pacientes com EA que requer tratamento 2004 População Prevalência de EA EA Grave EA grave 50% com Sx ,841, % 41,947 20, ,618, % 27,746 13, ,078, % 58,158 29, ,463, % 86,163 43,081 >75 17,830, % 273, ,701 Total 232,833, , ,708 Basiado nos dados de prevalência de EA de Olmsted County e em estatísticas sticas da o dos EUA; mais da metade dos pacientes com EA grave tem >75 anos de idade! d população dos EUA;

33 Pesquisa "Euro Heart" EA sintomática tica (idosos) Estenose Aórtica 75 anos N=408 EA não grave (n=114) EA grave (n=284) NYHA III :106 Sem sintomas N=68 Sintomas N=216 NYHA IV : 36 Angina : 148 Sem Intervenção Intervenção N=72 (33%) N=144 (67%) Iung, B, et al. Eur Heart J 2005;26: /3 dos pacientes idosos com EA e com Sx não são tratados

34 PVT-Edwards Valva cardíaca aca percutânea Dispositivo Cribier-Edwards 1a. geração poliuretano 2a. geração pericárdio rdio bovino Valva de pericárdio rdio eqüino stent de metal inox diâmetros de 23/26mm balão-expansível AVA = cm 2

35 SISTEMA Percutâneo da CoreValve PARTE SUPERIOR: Aumenta a qualidade de fixação e ajusta o sistema. PARTE MEDIA: é contraída para poupar p as coronárias e também contém a valva PARTE INFERIOR: possui força radial elevada, expandindo os folhetos e evitando leak paravalvar Uma valva de tecido de pericárdio rdio suíno fixada à armação com suturas de PTFE

36 20% Absolute Reduction in Mortality at 1 Year All-Cau use Mortal lity, % All-Cause Mortality at 1 yr = 20.0% NNT = 5.0 pts 50.7% 30.7% Standard Therapy Edwards THV 20 HR [95% CI] = 0.55 [0.40, 0.74] P (log rank) < No. at Risk Months Edwards THV Standard Therapy

37 29% Absolute Reduction in Mortality or Repeat Hospitalization All-Caus se Mortality or Repeat Ho ospitalization, % No. at Risk at 1 yr = 29.1% NNT = 3.4 pts 71.6% 42.5% Standard Therapy Edwards THV 20 HR [95% CI] = 0.46 [0.35, 0.59] P (log rank) < Months Edwards THV Standard Therapy

38 PARTNER Regras de Colaboração Cirurgia Cardíaca Cardiologia Intervencionista

39 Definition of Resistant Hypertension Uncontrolled Hypertension Includes all patients who lack BP control on treatment, including inadequate Uncontrolled treatment regimens, poor adherence, undetected secondary Hypertension hypertension, and true treatment resistance 1 Resistant Hypertension Resistant Hypertension BP that remains above goal in spite of compliance with full doses of 3 antihypertensive medications of different classes; ideally, 1 of the 3 agents should be a diuretic 1 The treatment plan must include attention to lifestyle measures 2 Includes those patients who achieve BP control but require 4 antihypertensive agents to do so 1 1. Calhoun DA, et al. Circulation. 2008;117:e510-e Mancia G, et al. Eur Heart J. 2007;28:

40 MI Through 6 Months (ITT Interim Snapshot) Cohort B EXTEND 194-day HR 0.87 [0.24,3.12] p=0.82 * MI (%) % 3.0% Δ = 0.5% 2.5% Number at risk Time Post Index Procedure (Months) Time after index procedure (days) Cohort B EXTEND * P-value is not from formal hypothesis testing and is displayed for descriptive purpose only. ABSORB BVS is neither approved nor available for sale in the U.S.

41 ID TVR Through 6 Months (ITT Interim Snapshot) 10 ID D-TVR (% %) Cohort B EXTEND 194-day HR 0.33 [0.05, 2.38] p=0.25 * % Number at risk 0 Time Post Index Procedure (Months) Δ = 1.4% 0.6% Time after index procedure (days) Cohort B EXTEND * P-value is not from formal hypothesis testing and is displayed for descriptive purpose only. ABSORB BVS is neither approved nor available for sale in the U.S.