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Application of MCS for the Treatment of Advanced Heart Failure

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Application of MCS for the Treatment of Advanced Heart Failure

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Application of MCS for the Treatment of Advanced Heart Failure

  1. 1. 1 1 Application of MCS for the Treatment of Advanced Heart Failure John B. O’Connell MD Vice President, Medical Affairs Thoratec Corporation Thoratec Asia Pacific Mechanical Circulatory Support (MCS) Conference Agenda 15-­‐17 November, 2013 | Shangri-­‐La Rasa Sentosa Resort, Singapore
  2. 2. 2 Disclosures Forward-­‐Looking Statements This presenta,on includes forward-­‐looking statements, including our current expected ,melines for product development, clinical trials and commercializa,on. Forward-­‐looking statements should not be read as a guarantee of future performance or results, and may not necessarily be accurate indica,ons of the ,mes at, or by, which such performance or results will be achieved. Forward-­‐looking statements are based on informa,on available at the ,me those statements are made and/or management's good faith belief as of that ,me with respect to future events, and are subject to risks and uncertain,es that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-­‐looking statements. Important factors that could cause such differences include, but are not limited to those discussed from ,me to ,me in Thoratec’s public reports filed with the Securi,es and Exchange Commission, such as those discussed under the heading, “Risk Factors,” in Thoratec’s most recent annual report on Form 10-­‐K and quarterly report on Form 10-­‐Q, and as may be updated in subsequent SEC filings. These forward-­‐looking statements speak only as of the date hereof. Thoratec undertakes no obliga,on to publicly release the results of any revisions to these forward-­‐looking statements that may be made to reflect events or circumstances aSer the date hereof. Statement on Product Risk Please consult the HeartMate II and CentriMag Instruc,ons for Use, for indica,ons for use, contraindica,ons, warnings and adverse events. hp://www.thoratec.com/medical-­‐professionals/resource-­‐library/index.aspx. Individual experiences, symptoms, situa,ons and circumstances may vary. Possible serious adverse events include: neurological problems (such as stroke), infec,on, bleeding, device malfunc,on (pump replacement), kidney and liver dysfunc,on, right heart failure, depression or anxiety and death. Pipeline Programs Pipeline programs, including the HeartMate® III, HeartMate X, HeartMate PHP, the fully implantable system (FILVAS), and the Pocket Controller, are in development and not approved for use. Trademarks Thoratec, the Thoratec logo, HeartMate, and HeartMate II are registered trademarks of Thoratec Corpora,on. CentriMag and PediMag are registered trademarks of Thoratec LLC, and PediVAS is a registered trademark of Thoratec Switzerland GmbH.
  3. 3. 3 Disclosures • I am an employee of Thoratec • I am a heart failure cardiologist who after 33 years is tired of helplessly watching potentially productive people die of progressive HF and am pro-MCS • I have either developed or assisted in the development of advanced HF/VAD/Tx programs in multiple institutions globally (academic and community; several in the absence of transplant programs) 3
  4. 4. 4 HF in the US ~6.0 million Americans with HF (2.8% of adult US populaUon) – NHANES 2008 (2030 >18 million) • Only form of heart disease increasing in prevalence – Life6me risk at age 40 or 80 – 1 in 5 – 825,000 new cases/year – Contributes to 279,098 annual deaths (1 in 9 death cer6ficates men6on HF) – 1.023 million ADHF hospitaliza6ons each year • AQer normal delivery, most common cause of hospitaliza6on – 30 day readmission rate 23% (50% not seen by physician) – all cause penalized by Medicare to 2% of all reimbursement – 801,000 ambulatory visits – Mortality 50% at 5 years; 34% at 1 year aQer a single hospitaliza6on – #1 reason for hospitaliza6on of people > 65 yr. old • More costly than all forms of cancer combined • Largest federal Medicare (37¢/$1) and VA $ expenditure – Cost $30.7 billion ($69.7 billion by 2030 - $244/adult) Mul;ple sources primarily AHA Sta;s;cal Update 2014
  5. 5. 5 5 Chronic Heart Failure Care: We’ve come a long way… Thoratec Asia Pacific Mechanical Circulatory Support (MCS) Conference Agenda 15-­‐17 November, 2013 | Shangri-­‐La Rasa Sentosa Resort, Singapore
  6. 6. 6 Courtesy of Hector Ventura MD
  7. 7. 7 Osler’s Recommendations for Heart Failure • “Special care should be taken of the bowels” • “A cold tub in the morning, if unsuccessful a lukewarm tub at night” • “Young people should be allowed plenty of sleep including an hour’s rest in the middle of the day” • “The question of marriage is always a distressing one” • “During the winter months a change in climate is most helpful” • “Moderation in all things should be the motto of the patient” • “More violent sports, such as football and hockey, should be interdicted” • “Golf is a particularly suitable game for young men” • “Gymnastic movements may be employed” • “Dancing is allowed in moderation for young girls with simple mitral lesions…and the apex beat not very far out” Osler: The Principles and Prac;ce of Medicine, 8th ed 1913
  8. 8. 8 Hurst’s The Heart 1974 Treatment of HF • Decreased physical activity • Digitalis • Thiazides plus potassium • Change to furosemide if no response
  9. 9. ACCF/AHA 2013 HF Guidelines JACC 2013 5 June (E-Pub ) 9
  10. 10. Two Year Survival of “Triple Therapy” in CHF 10 JACC 2003;7:1234-1237
  11. 11. 11
  12. 12. Definition of Advanced Heart Failure: European Society of Cardiology* • Despite optimal (best tolerated) medical and device management: 12 – NYHA Class III-IV symptoms – Clinical signs of fluid retention and/or hypoperfusion – Objective evidence of severe LV dysfunction • LVEF < 0.30; pseudonormal or restrictive mitral inflow pattern on Doppler; high left or right sided filling pressures; elevated BNP – Severe reduction in exercise capacity • 6 MWT < 300 meters; pVO2 < 12-14 ml/kg/min – > 1 hospitalization in the past 6 months Eur Heart J 2007;9:684-­‐94. *Adopted by ACCF/AHA in 2013 chronic HF guideline
  13. 13. 13 For the Advanced Heart Failure Program: The True Failures! § CRT non-responders § Recurrent appropriate ICD discharges § HFpEF with tenuous fluid balance § Suboptimal neurohormonal inhibitor dosage limited by hypotension or cardiorenal syndrome § Require IV diuretics or thiazides with loop diuretics – diuretic resistance § Require IV inotropes § A recent HF hospitalization (34% one year mortality) § Persistent symptoms with ADLs despite optimal medical and device therapy § Multiple comorbidities
  14. 14. 14 Options for the Advanced Heart Failure Patient § Optimize neurohormonal inhibition and device therapy § High risk conventional cardiac surgery § Heart transplantation § Mechanical circulatory support § Palliative care/hospice (chronic IV inotropes)
  15. 15. 15 Heart Transplantation will never meet the demands
  16. 16. Even though transplants are considered the ‘gold standard’, the supply has been historically flat and limited 16 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Number of Heart Transplants Reported by Year1 “Proposing heart transplantaUon to cure heart failure is analogous to proposing the loZery to cure poverty” 3,514 awa it heart t ransplant aUon (Ma y 10, 2013 )1 2500 2000 1500 1000 500 0 1. UNOS Website: hap://optn.transplant.hrsa.gov 2. O’Connell Advanced Heart Failure Therapies Forum Atlanta 2013 -­‐ LW Stevenson2
  17. 17. 17 Heart Transplants in Major Metropolitan Statistical Areas (2010) MSA Population Transplants Per 100,000 New York 21,976,224 110 0.5 Los Angeles 17,775,984 143 0.8 Chicago 9,725,317 76 0.8 Philadelphia 6,382,714 98 1.5 Houston 5,641,077 107 1.9 Total 61,501,316 534 0.9
  18. 18. Defined Strategies for Durable VADs 18 • Bridge to Transplant (BTT)* – Inserted for short to intermediate term support in patients actively listed for transplant • Destination Therapy (DT)* – Inserted with the intention of long term support in patients who are not transplant candidates • Bridge to Recovery – Inserted for short term support in a condition that is anticipate to reverse • Bridge to Candidacy (Decision) – Inserted for support when ultimate therapy is not able to be determined at the time of implantation or contraindication for transplant could be ameliorated by MCS *only strategies recognized by payers
  19. 19. Continuous Flow LVADs 19
  20. 20. 20 HM II Competing Outcomes for BTT Starling et al J Am Coll Cardiol 2011;57:1890-8.
  21. 21. 21 HeartMate II Improvements in BTT Survival From clinical trial to commercial Use 85% 0 3 6 9 12 Months Percent Survival 100 90 80 70 60 50 40 30 20 10 0 P < 0.001 log-rank test Post-Trial (N=1496) Trial (N=486) 76% John, Naka, Smedira et al Ann Thor Surgery 2011
  22. 22. 22 ADULT HEART TRANSPLANTS: % of Patients Bridged with Mechanical Circulatory Support* (Transplants: 2000 – 2010) 50 40 30 20 10 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year % of patients J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
  23. 23. 23 Reasons for Transplant Exclusion in DT Supplementary Appendix -­‐ Slaughter et al N Engl J Med 2009;361:2241-­‐51. 1. Age (39%) 2. Obesity (12%) 3. Pulmonary Hypertension (9%) 4. IDDM (8%) 5. Renal failure (7%) Recent history of cancer (7%) Patient refuses transplant (7%) 6. Social issue/compliance (5%) PAD (5%) 8. Sensitization to potential donors (3%) 9. Other (3%)
  24. 24. Summary of DT Outcomes 100 90 80 70 60 50 40 30 20 10 24 DT Trial (n=133)1 90 + 2% 1Slaughter, Rogers, Milano NEJM 2009;361:2241-51 61 + 3% 92 + 2% 0 6 12 18 24 LVAD Destination Therapy (HMII Post Approval Study) 0 6 12 18 24 100 90 80 70 60 50 40 30 20 10 Jorde, ISHLT 2013 Months Percent Survival 0 DT Post Approval (n=247) 68 + 4% 58 + 4% 74 + 3% Remaining at Risk: 247 192 169 151 130 133 95 82 69 62 Months Percent Survival 0 Medical Management (REMATCH, NEJM 2001)
  25. 25. HM II Quality of Life & Functional Outcome Improvement 25 HM II DT trial • 100% of patients were NYHA Class IIIB/IV status at baseline • 81% of patients improved to NYHA Class I or II by 24 months BTT 6 minute walk test • 16% of patients were capable of completing the test at baseline • 94% of HeartMate II recipients completed the test at 6 months Park SJ, et al; Outcomes in advanced heart failure patients with LVAD for DT. Circ Heart Fail. 2012;5(2):241-248 John R, et al. Continuous flow LVAD outcomes in commercial use compared with the prior clinical trial. Ann Thorac Surg. 2011;92(4):1406-1413.
  26. 26. Projected VAD US market growth and impact of Destination Therapy U.S. Chronic VAD Implants vs. Heart Transplants, 2007-­‐2012 26 Projected U.S. Chronic VAD implants by Indica;on (Analyst Es;mates), 2013-­‐2016 5,935 3,702 5,089 2,895 2,193 4,468 2,365 2,103 DT 1,914 125 DesUnaUon Therapy centers in the US today ~3,400 ~2,750 VADs Transplants ~2,200 ~2,150 ~2,200 ~2,300 ~2,300 ~2,150 ~1,850 ~1,325 2007 2008 2009 2010 2012 2,233 2016 2013 2014 2015 3,906 1,993 Source: Thoratec Es6mates; Average analyst projec6ons for VAD market (Wells Fargo, JP Morgan, Credit Suisse, Oppenheimer) '13-'16 CAGR 15% 25% 4% BTT
  27. 27. 27
  28. 28. Timeframe for Definitive Interventions based on INTERMACS classifications 1 INTERMACS levels Brief descriptions Timeframe for definitive intervention Advanced NYHA Class III Exertion limited/ “Walking wounded” Exercise intolerant/ “House-bound” Recurrent decompen-sation/ “Frequent flyer” Stable but inotrope-dependent/ “Dependent stability” Progressive decline/ “Sliding on inotropes” Critical cardiogenic shock/ “Crash and burn” Transplan-tation or circulatory support not currently indicated Variable, depends upon nutrition, organ function, and activity Variable, depends upon nutrition, organ function, and activity Elective over weeks to months as long as treatment of episodes restores stable baseline, including nutrition Elective over a few weeks Needed within a few days Needed within hours 7 6 5 4 3 2 NYHA classifications Class III Class IIIb/IV Class IV AHA/ACC classification Stage C Stage D Note: This grid was based on the best interpretation of the information provided in the sources listed below Sources: “Heart Failure”. NEJM 2003; 348:2007-18. “On the Fledgling Field of Mechanical Circulatory Support”. JACC 2007; (50) 8. “Characteristics of Stage D heart failure: Insights from the Acute Decompensated Heart Failure National Registry Longitudinal Module (ADHERE LM)”. Am J Heart 2008; 155:341-9. INTERMACS Manual of Operations version 2.2, User’s Guide
  29. 29. Patient Selection and Outcomes of LVAD 29 Implantation for DT Lietz et al Circulation 2007 Vol 116
  30. 30. Courtesy of P. Eckman 30
  31. 31. Clinical Outcomes Based on INTERMACS Profile Group 1: INTERMACS 1 Group 2: INTERMACS 2 or 3 Group 3: INTERMACS 4-7 Length of Stay Post-VAD Actuarial Survival Post-VAD Less acutely ill, ambulatory patients in INTERMACS profiles 4-7 had better survival and reduced length of stay compared to patients who were more acutely ill in profiles 1-3. Boyle, Ascheim, Russo, et.al. JHLT. 2011; 30:4,
  32. 32. The Late Stage Heart Failure Patient • Severe exercise intolerance • Heart failure wasting syndrome • Cardiorenal syndrome • Right heart failure • Inotrope dependence Courtesy of J. Rogers
  33. 33. High Mortality Associated with Advanced Heart Failure Less Than a 10% Survival Rate *J Cardiac *N Engl J Med 2001; 345:1435-43 Failure 2003;9:180-7 *INTrEPID Trial1 *Survival with continuous inotropes 4 1 Rogers JG, Butler J, Lansman SL, et al. Chronic mechanical circulatory support for inotrope-dependent heart failure patients who are not transplant candidates: results of the INTrEPID trial. J Am Coll Cardiol. 2007;50(8):741-47.
  34. 34. VAD Recipient Selection by INTERMACS Profile A Dynamic Process 1.9 42.7 46.7 42.0 2006 2007 2008 2009 2010 Kirklin et al JHLT 2012;131:117-26. 40.8 45.2 38.8 7.8 5.8 0.0 35.6 9.6 7.3 1.8 0.6 29.3 15.2 9.1 1.21 .0 21.5 17.1 9.9 2.31 .7 12.3 25.3 13.9 3.2 2.0 InItnetremrmacasc sP rPorfoilfeilse 1123456- 6 % of total implants
  35. 35. Early Referral Suggested: AHA Statement Circulation 2012; 126 “Implantation of MCS in patients before the development of advanced HF (ie, hyponatremia, hypotension, renal dysfunction, and recurrent hospitalizations) is associated with better outcomes. Therefore, early referral of advanced HF patients is reasonable” (IIa; B)
  36. 36. Natural History of Heart Failure Goodlin SJ J Am Coll Cardiol 2009;54:386-96.
  37. 37. “Better to put the device in 5 months too early than 5 minutes too late…” Walter Dembitsky MD, Cardiac Surgery Sharp Memorial Hospital San Diego
  38. 38. Complementary Studies Exploring HeartMate II in Earlier-Stage Heart Failure Class IV (On Inotropes) 3 2 1 NYHA Class III Class IIIb Class IV (Ambulatory) INTERMACS Profiles 7 6 5 4 FDA Approval: Class IIIb / IV CMS Coverage: Class IV Currently Not Approved Limited Adoption Growing Acceptance
  39. 39. Adapted from Russell SD, Miller LW, Pagani FD. Advanced heart failure: a call to action. Congest Heart Fail. 2008;14:316-321 39 Ideal time for referral NYHA IV plus one of the fo llowing: § Inability to walk < 1 block without dyspnea § Intolerant or refractory to ACE-I / ARB / BB § Diuretic dose > 1.5mg/kg/d § One or more CHF related hospital admissions within 6 months in setting of medical and dietary compliance § Measured peak VO2 < 14 ml/kg/min or < 50% age-gender predicted on treadmill
  40. 40. The population of these patients is large: In the US, ~300K AHF patients 40 PotenUal VAD / TX paUent populaUon -­‐ NaUonal ~240 M US Popula6on ≥ 20 years old 6.24 M HF = 2.6% of the popula6on 3.12 M Systolic HF = 50% of HF popula6on 124,800 Adv. Stage C / NYHA IIIB Advanced Stage C = 3-­‐4% 156,000 Stage D / NYHA IV = 0.5-­‐5% 70,200 25% Accessible AHF Pa6ents Virginia PopulaUon 8M ~ 2400 VADs and ~550/yr Richmond MSA PopulaUon 1.25M ~375 VADs and ~90/yr 117 PaUents / 100,000 PopulaUon 30 PaUents / 100,000 PopulaUon Current es6mates of adult pa6ents with advanced heart failure (HF) in the United States, with projected leQ ventricular assist device (LVAD) candidates. U.S. popula6on es6mate is derived from U.S. Census data. Es6mate of HF prevalence is derived from latest American Heart Associa6on (AHA) sta6s6cs. Es6mates of HF with reduced ejec6on frac6on and preserved ejec6on frac6on based on popula6on studies. Es6mates of prevalence of HF stages and New York Heart Associa6on (NYHA) class derived from Ammar et al, Goda et al, and Ceia et al. Source: Mechanical Circulatory Support: A Companion to Braunwald’s Heart Disease; “25% Accessible AHF Pa6ents” from Thoratec es6mates AHF Pa;ents: Poten;al VAD / TX Pa;ents: Incidence: 7 / 100,000 each year
  41. 41. 41 HeartMate II Implants per 100,000 Population (2013) 20 Largest Metro Areas (US) ≈ 5 4 3 2 1 0 Detroit Minneapolis Baltimore St. Louis Tampa San Francisco Denver Los Angeles Philadelphia Dallas Houston Chicago San Diego Seattle Washington DC Miami Atlanta Boston Phoenix New York 30 Estimated Number of Candidates 30 / 100,000 29 28
  42. 42. 42 Outcomes Critical to the Success of LVAD Therapy • Survival (near term and long term) • Quality of Life • Adverse Events – Drive application and cost in part by accounting for readmissions • Application to the appropriate patient population
  43. 43. 43 Mechanical Support Devices ACUTE INTERMEDIATE CHRONIC Short-term Months to 1 year Months to 1-7+ years Bridge to Decision or Wean Bridge to Transplant Bridge to Transplant Destination Therapy CentriMag* PediMag PVAD HeartMate II *See slide #6 for U.S. Indica6ons for Use
  44. 44. Adverse Events in the ADVANCE Trial and CAP - HVAD 44 44 Slaughter et al J Heart Lung Transplant 2013;32:675-83.
  45. 45. N=1270 Walt Dembitsky– Presented at the Economic Summit on VADs, October 3, 2013
  46. 46. Walt Dembitsky– Presented at the Economic Summit on VADs, October 3, 2013 COST REDUCTION TARGETS
  47. 47. 47 Technologic Advances: Potential Impact on Adverse Events • Bleeding, Thrombosis, Anticoagulation (HM III) • Full magnetic levitation reduces blood trauma and less likely to cleave vWF • Pulsatility (HM III) • Reduce mucosal AVMs, AI, Stroke • Wash out reduces pump thrombosis • Full implantation (FILVAS – HM III) • Eliminate driveline infections • BiVAD (HM III) • RV failure, ventricular arrhythmia
  48. 48. There are a number of approaches you can take to manage these patients 48 Referring for Care • Begin active management of AHF population • Provide comprehensive educational program on AHF for CV staff • Target early referral of “frequent fliers” to outside AHF program Sharing Care Fully integrated MCS program • Begin caring for VAD patients post implant • Potentially invest in building a HF clinic • Explore adding additional AHF treatments, e.g., – IV diuretics – INR clinics – Other DM programs • Fully-integrate as an AHF program • Become an OHC • Serve as a referral center in the community
  49. 49. Shared Care provides Shared Benefits • Reduced travel time and increased convenience for routine monitoring appointments • Ability to maintain close relationship with their cardiologists • Reduced burden of ongoing patient care while still participating in maintaining strong outcomes • Drives program growth through deeper relationships with community cardiologists • Continued hands-on involvement in the care of their patients • Greater familiarity with the benefits of VAD treatment and quality-of-life (QoL) improvements
  50. 50. 50 50 Outcomes of Patients Implanted with a Left Ventricular Assist Device at Non-transplant Open Heart Surgery Centers Marc R. Katz, MD, MPH Bon Secours Heart and Vascular Institute, Richmond, VA ISHLT 2012
  51. 51. INTERMACS Profiles 51 Profile OHC N -­‐ 130 (%) TX Center N -­‐ 3067 (%) 1 9 (7) 409 (13) 2 50 (38) 1252 (41) 3 50 (38) 772 (25) 4 14 (11) 417 (14) 5 1 (1) 116 (4) 6 1 (1) 63 (2) 7 5 (4) 38 (1) 83% 79%
  52. 52. Survival 52 1.00 0.90 0.80 0.70 0.60 0.50 0.40 0.30 0.20 0.10 0.00 Total implants 267 (36% BTT) 0 1 2 3 4 5 6 7 8 9 10 11 12 Percent Survival Months Logrank Analysis P = 0.9859 Baseline 6 Month 12 Month N Survival N Survival N OHC 130 89% 64 83% 25 HTC 3067 88% 1864 82% 1012 Presented by Marc Katz MD OHC Summit Mar 2014
  53. 53. 53 And the therapy is no longer just in specialized, academic centers Na6onal Need Source: Centers as of October 2013; Shared Care as of July 2013 from Thoratec data on file; Thoratec Corpora6on; UNOS Transplant Centers Non-­‐Tx Centers Shared Care Sites As of October 2013: 169 US HMII Centers 125 DT-­‐CerUfied HMII Centers
  54. 54. Local/Regional VAD Centers of Excellence Networks Hub and Spoke model n Transplant center n Implanting Center n AHF Mgmt Center n Referral Practice n Out of Network Courtesy of Confidential F. Dennis property of Optum. Do Irwin not distribute MD, or reproduce Medical without express permission Director from Optum.
  55. 55. 55 The State of VAD Therapy Today • MCS is one of multiple options for managing AHF • Outcomes justify considering MCS earlier in the pathophysiologic perturbation • Continued technologic advances will justify application to a broader population • Support of controlled studies to assess the value of earlier implantation should be a priority • Destination Therapy is the major growth area in the US
  56. 56. 100 90 80 70 60 50 40 30 20 10 56 Summary of Post Approval Outcomes* 85% 0 3 6 9 12 *John et al Ann Thorac Surg 2011 **Jorde et al J Am Coll Cardiol 2014 DT Trial (n=133)1 90 + 2% 1Slaughter, Rogers, Milano NEJM 2009;361:2241-51 61 + 3% 92 + 2% 0 6 12 18 24 Months Percent Survival 100 90 80 70 60 50 40 30 20 10 0 DT Post Approval (n=247) 68 + 4% 58 + 4% 74 + 3% Remaining at Risk: 247 192 169 151 130 133 95 82 69 62 Months Percent Survival 0 P < 0.001 log-rank test Post-Trial (N=1496) Trial (N=486) 76% BTT* DT** *derived from INTERMACS

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