1. Dr. Prashant Jagtap Sr. Interventional Cardiologist Wockhardt Hospitals , NAGPUR Newer Trends in Interventional Cardiology

2. Cardiovascular Disease1.2 Million Heart Attacks 3. Outline 4. Outline 5. 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 6. Coronary Atherosclerosis 7. Angiogram

Visualize blockages

Catheter is inserted into the leg or arm

Contrast dye for visualization

X-ray is taken of the arteries

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

EKG

Stress test

Echocardiograph

Blood work

8. Treatment Algorithm 9. Treatments for CAD Health Care Guideline: Stable Coronary Artery Disease.Institute for Clinical Systems Improvement . !3th ed., 2009 10. History of AngioplastyFirst stainless steel Stent inserted in human artery 1986 2006 30 patients enrolled in the first ever human clinical trial testing a fullyBioabsorbable Drug-eluting Stent(ABSORB trial, Abbott) Drug eluting stents introduced to EU and USA markets 2001-2003 1999 First bioabsorbable PLLA stent in human coronary arteries (Igaki-Tamai) 1977 First Coronary Angioplasty Dr. Andreas Gruentzig 11. Evolution of Angioplasty Lobodzinski, S. S. (2008). Bioabsorbable Coronary Stents.Cardiology Journal , 15(6), 569-571.Pros Cons Balloon Angioplasty

Enlarges narrow artery

Relieves chest pain

Elastic recoil of artery

High early restenosis

Bare Metal Stents

Permanently prop open vesselless 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 metalreduce restenosis

Incomplete healinginduce chronic inflammatory response

Increased risk of thrombosis

12. 13. Video: Stenting Procedure

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

14. Outline 15. Three Generations of StentsOrmiston et al. (2007). Catheterization and Cardiovascular Intervention, 69: 129-131 16. Restenosishttp://www.evgn.org/home/imagesnew/stentv2web.jpg Restenosis andNeo-Intimal HyperplasiaTissue re-growth into the stent area 17. Drug Eluting Stents: The Problem Curfman GD, Morrissey S, Jarcho JA, Drazen JM. Drug-eluting coronary stentspromise and uncertainty.NEJM . 2007;256:1059-1060 18. 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. 19. 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. 20. DES: The Market LeaderXience outperforms Taxus Express in SPIRIT IV, Dave Fornell, Diagnostic and Invasive Cardiology. Retrieved on Nov 26th, 2009 from http://www.dicardiology.net/node/34463/3Sipkoff, 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 21. 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 22. Outline 23. Kirk. N. Garratt. (2009). Update on DES and Biodegradable Stents 2009 24. BVS Functionality Ormiston et al. (2007). Catheterization and Cardiovascular Intervention, 69: 129-131 25. 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

Ormiston et al. (2007). Catheterization and Cardiovascular Intervention, 69: 129-131 26. BVS vs. DES:The Thrombosis Issue Curfman GD, Morrissey S, Jarcho JA, Drazen JM. Drug-eluting coronary stentspromise and uncertainty.NEJM . 2007;256:1059-1060 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 andvery late ST No reports of ST fromphase I study 27. Advantages of the BVS Stent 28. 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%)

Ormiston et al. (2007). Catheterization and Cardiovascular Intervention, 69: 129-131 29. 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. 30. Second Generation BVS Stent

More even support of arterial wall

Lower late stent area loss

Higher radial strength

Ormiston et al. (2007). Catheterization and Cardiovascular Intervention, 69: 129-131 31. Regulatory Pathway for BVS Based on Drug-Eluting StentsDrug Eluting StentStent Platform and Delivery SystemDrug Carrier Polymer PMA Class III DeviceSource: Food and Drug Administration, U.S.A Center for Devices and Regulatory HealthCenter for Drug Evaluation and Research 32. Bioabsorable Vascular Solution 33. Bioresorbable Device Components Bioresorbable Coating

PDLLA coating

Fully biodegradable

Similar dose and release rate to XIENCE V

Everolimus

Poly (Lactic Acid) (PLLA)

Naturallyabsorbed, fullymetabolized

Bioresorbable Device Platform MULTI-LINK VISION Stent Delivery System

Sevengenerations of MULTI-LINKsuccess

World-classdeliverability

All illustrations are artists renditions 34. Bioabsorbable Vascular Solutions Program Goals

Naturally absorbed,fully metabolized

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

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

Compatible withCT imaging

35. Bioresorbable Polymer

Everolimus/PDLLA Matrix Coating

Thin coating layer

Amorphous (non-crystalline)

1:1 ratio of Everolimus/PLA matrix

Conformal Coating, 2-4 m thick

Controlled drug release

PLLA Backbone

Highly crystalline

Provides device integrity

Processed for increased radial strength

Polymer backbone Drug/polymer matrix 36. Performance Criteria for a Fully Bioresorbable Device 1 3 6 2 Yrs Mos Forrester JS, et al.,J. Am. Coll. Cardiol.1991; 17: 758. Full Mass Loss & Bioresorption Platelet Deposition Leukocyte Recruitment SMC Proliferation and Migration Matrix Deposition Re-endothelialization Vascular Function Everolimus Elution Support Mass Loss 37. ABSORB Cohort A Excellent 3-Year Clinical Data

ABSORB Cohort A3-Year Data:

• One MACE* (NQMI); No additional MACE between 6 months and 3 years

• No stent thrombosisthrough 3 years

• Lumen enlargement from6 months to 2 years byIVUS and OCT

• Restoration of vasomotion including the treated segment

• Bioabsorption of device

38. Key Players in the Bioabsorbable Stent Market 39. Outline 40. Quantitative Analysis Assumptions

Costs remain the same in:

Cost differential occurs in:

Procedure

Initial hospitalization

Routine follow-ups

Acquisition of stent

Serious adverse events

Anti-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. CostTotal= CostStent+ CostSerious Adverse Events+ CostDAT 41. Cost-Benefi