A National Cardiogenic Shock Initiative (CSI):

Transcription

1 A National Cardiogenic Shock Initiative (CSI): Insights from the Impella Quality (IQ) Program, cvad Registry and the Detroit CSI Experience William O Neill, MD, FACC Medical Director Structural Heart Disease at Henry Ford Hospital, MI

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit Company None

3 AMI Shock Mortality Unchanged in > 20 years US AMI/CGS cases per year 1, High In-Hospital Mortality During AMI Cardiogenic Shock 3 N = 23, Sandhu A,, et al.. Circulation, 2015;132: Acute Cardiac Assist Report, Health Research International August Jeger, et al. Ann Intern Med. 2008

4 Abiomed IQ Program Real World Clinical Evidence Reported Usage in IQ Database 1 N=61286 cvad Registry Data 2 N=3729 HRPCI Elective & Urgent 48% (n=29,213) Other 19% (n=11,419) Cardiogenic Shock 34% (n=20,654) HRPCI Elective & Urgent 46% (n=1705) Cardiogenic Shock 40% (n=1490) Other 14% (n=534) Observational Quality Assurance Database IRB Exempt / HIPAA Compliant 1,010 US Impella Centers; Reviewed by Abiomed Heart Team Physicians All Devices, All Indications FDA Pre/Post Market Study Prospective registry; one year follow-up; academic core labs FDA Validated/audited for Pre-Market Approval (PMA) & Post- Approval Studies (PAS) Used for expansion of FDA indications for device use Used to assess best practices adoption & outcomes and confirm appropriate use of the Impella 1. Abiomed Impella Quality (IQ) Database, Danvers MA 2. cvad Registry Data of Patients Undergoing PCI for Acute Myocardial Infarction Complicated by Cardiogenic Shock as of September 2017

5 AMI/CGS Impella Patient Demographics IQ Database 1 cvad Registry 2 Age Mean: 63.8 y/o Range: (9 99) Gender 73% Male Duration Of Support Mean: 2.9 Days Median: 1.9 Days Max: 108 Days Survival to Explant Age Mean: 66.3 y/o Range: (19 95) Gender 76% Male Duration Of Support Mean: 1.63 Days Median: 1.1 Days N=3549 N=9693 Max: 10.6 Days Survival to Explant, Discharge & 30 days 1. Abiomed Impella Quality (IQ) Database, Danvers MA 2. cvad Registry Data of Patients Undergoing PCI for Acute Myocardial Infarction Complicated by Cardiogenic Shock as of September 2015

6 # of Sites Variation in Impella AMI/CGS Outcomes Distribution of Impella Site Outcomes sites supporting >6 AMICS patients, 2,408 patients total Bottom quintile of sites have mean survival of 25% Top quintile of sites have mean survival of 77% 2 Mean 51% 0% 20% 40% 60% 80% 100% Survival to Explant 2 1. Data on file. Abiomed Impella Quality(IQ)Data, AMI/CGS Apr 2015 Mar Danvers, MA: Abiomed. 2. Greater than 90% of survivors were explanted with native heart recovery

7 Mortality 32% Increased Inotrope Exposure is associated with Mortality in AMI/CGS Mortality and Number of Inotropes from cvad Registry 1 54% P<0.001 (N=287) 65% 65% 74% Number of Inotropes/Pressors Samuels LE et al, J Card Surg Basir M, Schreiber T, Grines C, et al. Effect of Early Initiation of Mechanical Circulatory Support on Survival in Cardiogenic Shock. Am. J. of Cardiology, 2016

8 Impella Pre-PCI associated with Improved Survival in AMI/CGS IQ Database 1 cvad Registry 2 60% 65% 54% P< % P<0.003 N=4364 IABP and/or Inotropes Pre-PCI N=3678 Impella Pre-PCI N=91 IABP and/or Inotropes Pre-PCI N=63 Impella Pre-PCI 1. Abiomed Impella Quality (IQ) Database, US AMI/CGS Apr 2009 Oct Survival to Explant. Danvers, MA: Abiomed. 2. O Neill et al., J Int Cardiol 2014;27:1-11. Survival to hospital discharge

9 Meta-Analysis: Early vs Late Support Flaherty MP, et al., Early Initiation of Impella in Acute Myocardial Infarction Complicated by Cardiogenic Shock Improves Survival, JACC Cardiovascular Interventions 2017; 10:1803-6

10 Hemodynamic Monitoring associated with Improved Survival in AMI/CGS IQ Database 1 62% cvad Registry 2 76% 68% P= % P< N=10876 N=8018 N=634 N=516 No Hemodynamic Monitoring Hemodynamic Monitoring No Hemodynamic Monitoring Hemodynamic Monitoring 1. Abiomed Impella Quality (IQ) Database, US AMI/CGS Apr 2009 Oct Survival to Explant. Danvers, MA: Abiomed. 2. cvad survival to explant

11 Detroit Cardiogenic Shock Initiative DETROIT CSI

12 DETROIT CSI PROTOCOL

13 DETROIT CSI PROTOCOL

14 DETROIT CSI PROTOCOL

15 100% Native Heart Recovery in Survivors Outcomes (N=41 patients) 51% 85% 76% 100% Native Heart Recovery In surviving Patients (31/31) Survival to Explant Metro Detroit Before Study Survival to Explant Detroit CSI Survival to Discharge Detroit CSI 1. Abiomed Impella Quality (IQ) Database, Jan 2015 to July 2016 for Aggregate DTW Metro Hospitals AMI/CGS Survival to Explant 2. W. O Neill, M. Basir, S. Dixon, K Patel, T Schreiber, S. Almany; in press, CCI

16 Physicians from over 40 hospitals have contacted us about joining Detroit CSI First site outside of Detroit launched in August: Mercy Fitzgerald Hospital in Philadelphia Similar to Detroit, regional groups are forming to work together on CGS National Shock Initiative Detroit Cardiogenic Shock Initiative

17 Increasing Standardization of Practice in Top Quintile of Sites 100.0% Survival to Explant by Site 80.0% 60.0% 40.0% 20.0% 0.0% Data on file Abiomed Impella Quality (IQ) Data, AMI/CGS, Jan 2009-Oct 2017, Danvers, MA, Abiomed sites supporting >6 AMICS patients,1184 patients total since Jan 1,2016

18 National Outcomes Improving Distribution of Impella Site Outcomes 1 # of Sites 51% 62% 22% relative improvement in overall outcomes since March, 2016 (p<0.0001) 2 0% 20% 40% 60% 80% 100% Survival to Explant 1. Data on file. Abiomed Impella Quality(IQ)Data, AMI/CGS Apr 2016 Sept Danvers, MA: Abiomed sites supporting >6 AMICS patients, 7,483 patients total since March 2016

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20 Conclusions AMI CGS mortality remains unchanged despite major advances in cardiac care in past 20 years There is a wide institutional variation in AMI CGS outcomes with Impella use Key Observations Associated with Improved Outcomes: Reduced exposure to high dose inotropes Impella use prior to PCI Protocol using hemodynamic monitoring to guide escalation and weaning Prospective, systematic adoption of best practices markedly improves survival and native heart recovery Nationwide outcomes with Impella are improving with trends toward increased adoption of best practices

21 Thank You

22 APPENDIX

23 Impella Utilization in AMI Shock Total AMI/CGS US Patients 1, % 45% % IABP Supported Patients 2 42% 41% 39% 41% 42% 42% % Impella Supported Patients 3 0% 1% 1% 2% 2% 3% 4% 6% Acute Cardiac Assist Report, Health Research International August Sandhu A, et al. Circulation, 2015;132: Data on file. Abiomed Impella Quality (IQ) Database, US AMI/CGS Jan 2009 Dec 2016.

24 Randomization in Cardiogenic Shock is Challenging Prospective Impella Trials In Emergent Settings Study Trial ID Condition Pts Required (n) Pts Enrolled (n) Duration (months) Status Reason for Discontinuation FRENCH TRIAL (2006) NCT AMI CS Discontinued Low Enrollment ISAR-SHOCK (2006) NCT AMI CS Completed N/A IMPRESS in STEMI (2007) NTR1079 trialregister.nl STEMI Pre-CS Discontinued Low Enrollment RECOVER I FDA (2008) NCT PCCS Up to Completed N/A RECOVER II FDA (2009) NCT AMI CS Discontinued Low Enrollment RELIEF I (2010) NCT ADHF Discontinued Low Enrollment DANSHOCK (2012) NCT AMI CS Enrolling N/A IMPRESS Severe Shock (2016) NTR3450 Cardiac Arrest > Discontinued Low Enrollment

25 Impella Quality (IQ) Database Methods Abiomed clinical personnel collecting real world data from >98% of US cases since 2009; >60,000 patients >20,000 patients with AMI-CGS FDA Approval 2016, AMI/CGS therapy and heart recovery Audited by Abiomed Heart Team (Cardiologists and CV Surgeon) HIPAA compliant data collection, FDA Maude protocol compliant Exempt status by Henry Ford Hospital IRB Survival tracked to device explant

26 cvad Registry Prospective registry of Impella with one year follow-up and academic core labs Validated & audited by FDA for Pre-Market Approval (PMA); Used for expansion of FDA indications for device use Validated & audited by FDA for Post-Approval Studies (PAS) of Impella s indications for Protected PCI, Cardiogenic Shock and Right Heart Failure Collection of Real-World Data to develop Real-World Evidence consistent with FDA s evolving interest for post market surveillance and provide comparisons to prior FDA studies Used to assess best practices adoption & outcomes (such as CSI protocol in AMI cardiogenic shock) and confirm appropriate use of the Impella

27 ABIOMED S IMPELLA QUALITY (IQ) ASSURANCE PROGRAM Abiomed's IQ Database is a collection of real-world, observational quality assurance data on over 95% of Impella patients since the Impella 2.5 heart pump's introduction to the United States in The IQ database, combined with additional clinical data collected in the cvad Registry and FDA pre- and postmarket studies, is helping to identify best practices and protocols that are linked to the highest survival and native heart recovery rates at hospitals utilizing Impella heart pumps. The data contained in the IQ Assurance Database is useful in establishing certain trends associated with the use of Impella. The data contained therein is not pre-specified or statistically-powered and no statistical conclusions can be drawn from the hypothesis-generating information.

28 Impella Device Indication & safety info. INDICATIONS FOR USE Protected PCI The Impella 2.5 and Impella CP Systems are temporary ( 6 hours) ventricular support devices indicated for use during high-risk percutaneous coronary interventions (PCI) performed in elective or urgent, hemodynamically stable patients with severe coronary artery disease and depressed left ventricular ejection fraction, when a heart team, including a cardiac surgeon, has determined high-risk PCI is the appropriate therapeutic option. Use of the Impella 2.5 and Impella CP Systems in these patients may prevent hemodynamic instability, which can result from repeat episodes of reversible myocardial ischemia that occur during planned temporary coronary occlusions and may reduce peri- and post-procedural adverse events. Cardiogenic Shock The Impella 2.5, Impella CP, Impella 5.0, and Impella LD Catheters, in conjunction with the Automated Impella Controller (collectively, "Impella System Therapy"), are temporary ventricular support devices intended for short term use ( 4 days for the Impella 2.5 and Impella CP, and 6 days for the Impella 5.0, and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (< 48 hours) following acute myocardial infarction or open heart surgery as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures (including volume loading and use of pressors and inotropes, with or without IABP). The intent of Impella System Therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function. Important Risk Information for Impella devices CONTRAINDICATIONS The Impella 2.5, Impella CP, Impella 5.0 and Impella LD are contraindicated for use with patients experiencing any of the following conditions: Mural thrombus in the left ventricle; Presence of a mechanical aortic valve or heart constrictive device; Aortic valve stenosis/calcification (equivalent to an orifice area of 0.6 cm2 or less); Moderate to severe aortic insufficiency (echocardiographic assessment graded as +2); Severe peripheral arterial disease precluding placement of the Impella System; Significant right heart failure*; Combined cardiorespiratory failure*; Presence of an Atrial or Ventricular Septal Defect (including post-infarct VSD)*; Left ventricular rupture*; Cardiac tamponade* * This condition is a contraindication for the cardiogenic shock indication only. POTENTIAL ADVERSE EVENTS Acute renal dysfunction, Aortic valve injury, Bleeding, Cardiogenic shock, Cerebral vascular accident/stroke, Death, Hemolysis, Limb ischemia, Myocardial infarction, Renal failure, Thrombocytopenia and Vascular injury In addition to the risks above, there are other WARNINGS and PRECAUTIONS associated with Impella devices. Visit and to learn more.

29 Right-Side Support Indication & safety info. INDICATIONS FOR USE The Impella RP System is indicated for providing temporary right ventricular support for up to 14 days in patients with a body surface area 1.5 m 2, who develop acute right heart failure or decompensation following left ventricular assist device implantation, myocardial infarction, heart transplant, or open-heart surgery. Important Risk Information for Impella RP System CONTRAINDICATIONS The Impella RP System is contraindicated for patients with the following conditions: Disorders of the pulmonary artery wall that would preclude placement or correct positioning of the Impella RP device. Mechanical valves, severe valvular stenosis or valvular regurgitation of the tricuspid or pulmonary valve. Mural thrombus of the right atrium or vena cava. Anatomic conditions precluding insertion of the pump. Presence of a vena cava filter or caval interruption device, unless there is clear access from the femoral vein to the right atrium that is large enough to accommodate a 22 Fr catheter. POTENTIAL ADVERSE EVENTS The potential adverse effects (eg, complications) associated with the use of the Impella RP System: Arrhythmia, Atrial fibrillation, Bleeding, Cardiac tamponade, Cardiogenic shock, Death, Device malfunction, Hemolysis, Hepatic failure, Insertion site infection, Perforation, Phlegmasia cerulea dolens (a severe form of deep venous thrombosis), Pulmonary valve insufficiency, Respiratory dysfunction, Sepsis, Thrombocytopenia, Thrombotic vascular (non-central nervous system) complication, Tricuspid valve injury, Vascular injury, Venous thrombosis, Ventricular fibrillation and/or tachycardia. In addition to the risks above, there are other WARNINGS and PRECAUTIONS associated with Impella RP. Visit to learn more.