Newer trends in interventional cardiology

transcript

Dr. Prashant JagtapSr. Interventional CardiologistWockhardt Hospitals , NAGPUR

Newer Trends in Interventional Cardiology

Cardiovascular Disease

1.2 Million Heart

Attacks

Outline

Coronary Artery Disease

Result of accumulation of atherosclerotic plaque

Arteries supplying the heart muscle are occluded

Oxygen-rich blood does not reach the heart

Symptoms are angina and myocardial infarction

http://www.nhlbi.nih.gov/health/dci/Diseases/Cad/CAD_WhatIs.html

Coronary Atherosclerosis

AngiogramVisualize blockagesCatheter is inserted into the

leg or armContrast dye for visualizationX-ray is taken of the arteries

Health Care Guideline: Stable Coronary Artery Disease. Institute for Clinical Systems Improvement. !3th ed., 2009

Other TestsEKGStress testEchocardiographBlood work

Treatment Algorithm

Treatments for CAD

Health Care Guideline: Stable Coronary Artery Disease. Institute for Clinical Systems Improvement. !3th ed., 2009

History of Angioplasty First stainless steel Stent inserted in human artery

30 patients enrolled in the first ever human clinical trial testing a fully Bioabsorbable Drug-eluting Stent (ABSORB trial, Abbott)

Drug eluting stents introduced to EU and USA markets

2001-2003

First bioabsorbable PLLA stent in human coronary arteries (Igaki-Tamai)

First Coronary AngioplastyDr. Andreas Gruentzig

Evolution of Angioplasty

Pros Cons

Balloon Angioplasty

-Enlarges narrow artery-Relieves chest pain

-Elastic recoil of artery -High early restenosis

Bare Metal Stents

-Permanently prop open vessel less elastic recoil-Lower early restenosis

-Metal scars endothelial tissue-Leads to neointimal growth response-Contributes to late restenosis

Drug Eluting Stent

-Antiproliferative drug mitigates adverse response to metal reduce restenosis

-Incomplete healing induce chronic inflammatory response -Increased risk of thrombosis

Lobodzinski, S. S. (2008). Bioabsorbable Coronary Stents. Cardiology Journal, 15(6), 569-571.

Video: Stenting Procedure

http://www.youtube.com/watch?v=gvRtP3wl_AY

Outline

Three Generations of Stents

Ormiston et al. (2007). Catheterization and Cardiovascular Intervention, 69: 129-131

Restenosis

http://www.evgn.org/home/imagesnew/stentv2web.jpg

Restenosis and Neo-Intimal Hyperplasia

Tissue re-growth into the stent area

Drug Eluting Stents:The Problem

Curfman GD, Morrissey S, Jarcho JA, Drazen JM. Drug-eluting coronary stents—promise and uncertainty. NEJM. 2007;256:1059-1060

Stent Thrombosis

Cola, C. Brugaletta, S., Yuste, V. M., Campos, B., Angiolillo, D. J. & Sabete, M. (2009). Diabetes mellitus: a prothrombotic state implications for outcomes after coronary revascularization. Vascular Health and Risk Management, 5, 101-119.

Thrombosis: Early vs. Late Events

Cola, C. Brugaletta, S., Yuste, V. M., Campos, B., Angiolillo, D. J. & Sabete, M. (2009). Diabetes mellitus: a prothrombotic state implications for outcomes after coronary revascularization. Vascular Health and Risk Management, 5, 101-119.

DES: The Market Leader

Xience outperforms Taxus Express in SPIRIT IV, Dave Fornell, Diagnostic and Invasive Cardiology. Retrieved on Nov 26th, 2009 from http://www.dicardiology.net/node/34463/3 Sipkoff, M. (2009, Jul 1). Drug-eluting stents make a comeback. ModernMedicine. Retrieved online http://www.modernmedicine.com/modernmedicine/Modern+Medicine+Feature+Articles/Drug-eluting-stents-make-a-comeback/ArticleStandard/Article/detail/607928

Stents: Product Label – On or Off?

• FDA approved lesion parameters– Lesion length < 30 mm– Vessel diameter: 2.5 mm to

3.75mm

• Off label examples– Lesion in by pass graft– Bifurcation lesion

Source: FDA Guidance Document on Drug Eluting Stents

Outline

Kirk. N. Garratt. (2009). Update on DES and Biodegradable Stents 2009

BVS Functionality

The BVS Stent: Polymers• PLLA (Poly-L-Lactic Acid)

backbone

• PDLLA (Poly-D,L-lactic acid) coating

• Both degrade to lactic acid

• Entire stent absorbs in 2 years

BVS vs. DES: The Thrombosis Issue

Drug – Eluting Stent Bioabsorbable stent

Polymer not biocompatible Polymers are biocompatible

All the drug is not eluted 100% drug is eluted in 4 months

Incomplete healing of endothelium

Complete healing of endothelium

Problems with late and very late ST

No reports of ST from phase I study

Curfman GD, Morrissey S, Jarcho JA, Drazen JM. Drug-eluting coronary stents—promise and uncertainty. NEJM. 2007;256:1059-1060

Advantages of the BVS Stent

ABSORB: First In-man Study

• 30 patients, single de novo lesions

• Composite endpoint: – Cardiac death, Myocardial Infarction, Target

lesion revascularization (TLR)

• Secondary end points:– In-stent late loss, late ST

• Results: - 0% thrombosis, 0% TLR, MACE (3.3%)

Bare-Metal vs. Drug-Eluting vs. Bioabsorbable Stents

Results taken from the 2006 Spirit IV trial (3, 690 patients), 2002 Sirius trial (1,058 patients) and the Absorb trial (30 patients). All trials were done in patients with similar lesions. The results reported are after 1-year follow-up.

Second Generation BVS Stent

More even support of arterial wall

Lower late stent area loss

Higher radial strength

Regulatory Pathway for BVS Based on Drug-Eluting Stents

Drug Eluting Stent

Stent Platform and Delivery

System

DrugCarrier

“Polymer”

PMA – Class III Device

Source: Food and Drug Administration, U.S.A

Center for Devices and Regulatory

Health

Center for Drug

Evaluation and Research

Bioabsorable Vascular Solution

Bioresorbable Device Components

Bioresorbable Coating

• PDLLA coating

• Fully biodegradable

• Similar dose and release rate to XIENCE V

Everolimus

• Poly (Lactic Acid) (PLLA)

• Naturally absorbed, fully metabolized

Bioresorbable Device Platform

MULTI-LINK VISION Stent Delivery System

• Seven generations of MULTI-LINK success

• World-class deliverability

All illustrations are artists’ renditions

• Naturally absorbed, fully metabolized

• Acutely perform like a metallic DES: deliverability, conformability, radial strength

• Long-term: restore vasomotion, improved clinical outcomes, lower restenosis

• Compatible with CT imaging

Bioabsorbable Vascular Solutions Program Goals

Bioresorbable Polymer

Everolimus/PDLLA Matrix Coating

Thin coating layerAmorphous (non-

crystalline)1:1 ratio of Everolimus/PLA

matrixConformal Coating, 2-4 m

thickControlled drug release

PLLA BackboneHighly crystallineProvides device integrityProcessed for increased

radial strength

Polymer backbone

Drug/polymer matrix

Performance Criteria for a Fully Bioresorbable Device

1 3 6 2 Yrs

Full Mass Loss & Bioresorption

Platelet Deposition

Leukocyte Recruitment

SMC Proliferation and Migration

Matrix Deposition

Re-endothelialization

Vascular Function

Everolimus Elution

Support

Mass Loss

Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

• ABSORB Cohort A 3-Year Data:– One MACE* (NQMI); No

additional MACE between 6 months and 3 years

– No stent thrombosis through 3 years

– Lumen enlargement from 6 months to 2 years by IVUS and OCT

– Restoration of vasomotion – including the treated segment

– Bioabsorption of device

ABSORB Cohort AExcellent 3-Year Clinical Data

Key Players in the Bioabsorbable Stent Market

Outline

Quantitative Analysis Assumptions

Costs remain the same in:

Cost differential occurs in:

ProcedureInitial

hospitalizationRoutine follow-ups

Acquisition of stentSerious adverse

eventsAnti-platelet

therapy (DAT)

Cohen, D.J. et al. Cost Effectiveness of Sirolimus-Eluting Stents for Treatment of Complex coronary Stenoses. Circulation 2004; 110: 508-514.

Cost Total = Cost Stent + Cost Serious Adverse Events + Cost DAT

Cost-Benefit Analysis of BVS on Thrombosis and TLR Rates

Filion, K. B., Roy, A. M., Baboushkin, T., Rinfret, S. & Eisenberg, M. J. (2009). Cost-Effectiveness of Drug-Eluting Stents Including the Economic Impact of Late Stent Thrombosis. The American Journal of Cardiology, 103(3): 338-44.

Price of stents:

$2200 DES (Cypher)

$3000 BVS (Abbott)

Cost Effectiveness(CE) Analysis

Incremental Cost Effectiveness Ratio (ICER)

The lower the ICER, the better

Compare CE of BVS to DES

Equations for ICER Calculation

ICER – Incremental Cost Effectiveness Ratio BVS – Bioabsorbable Stents SAE – Serious Adverse Events BMS – Bare Metal StentsDAT – Dual Anti-platelet Therapy Freq - Frequency

Historical Precedence

ICER (BMS vs Balloon) $5000/SAD Avoided

ICER (DES vs BMS) $5098/SAD Avoided

ICER of BVS with Three Estimates of Study Outcome

Stent Feature Matrix

Bare-Metal Stents

Drug-eluting Stent

Bioabsorbable drug- eluting Stent

Reduced Dual-Antiplatelet Therapy

No neointimal hyperplasia

Restoration of Vasomotion

Material (Biocompatible)

Lobodzinski, S. S. (2008). Bioabsorbable Coronary Stents. Cardiology Journal, 15(6), 569-571.

Conclusion Large coronary stent market BVS improves on thrombosis

BVS has the potential to be economically feasible for device manufacturer and healthcare insurers

Acknowledgements Dr. Jayson Parker, M.Biotech

Dr. Michael Kutryk, St. Michael’s Hospital

Dr. Geoff Puley, Trillium Health Center

Jennie Kim, Abbott Vascular, U.S.A

Dr. Robert Cottone, Orbis Neich

Dr. Janarthan Nikhil, Credit Valley

Dr. Sidney Kremer, Credit Valley

Dr. Kirandeep Nagi, Credit Valley

Joanne Barrette, Abbott Vascular

Margaret Chong, Abbott Vascular

Dr. Jeffrey Pang, Sunnybrook Health Sciences Center

Dr. Linda Mackeigan, Leslie Dan School of Pharmacy

Dr. Peter Seidelin, Toronto General Hospital

Breakthrough Technology for Mitral Regurgitation

MITRACLIPvideo

Mitraclip.flv

Thank you for listening.

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