1 TREATMENT OF HIGHER RISK PATIENTS INTRODUCTION TO PROTECTED PCI WITH IMPELLA
FDA APPROVES IMPELLA FOR HIGH-RISK PCI 2 Impella is the only hemodynamic support device proven safe and effective in elective and urgent High-Risk PCI patients Impella is designed to protect the patient hemodynamically during a high-risk procedure
IMPELLA DEVICE INDICATION & SAFETY INFO. 3 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, 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 or in the setting of cardiomyopathy, including peripartum cardiomyopathy, or myocarditis 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 http://www.abiomed.com/important-safety-information to learn more.
DATA SUPPORTING PROTECTED PCI INDICATION 4 Scientific Evidence to Support PMA Applications* Total Number of Patients in the Cohort Number of Impella Protected PCI Patients Severely Reduced LVEF <35% Protect I 20 20 Protect II 452 225 U.S. Impella Registry 1,322 709 Literature review 2,537 756 Mild, Moderately Reduced LVEF >35% cvad Registry Study 693 464 / 229 LVEF< 35% LVEF> 35% Total 5,024 2,403 * Patient data may be provided in multiple PMA applications
5 PROTECTED PCI WITH IMPELLA CLINICAL DATA & GUIDELINES
GROWING POPULATION APPROPRIATE FOR PCI 6 Surgical Ineligibility Prior Cardiac Surgery Heart Failure Diabetes Advanced Age Unstable Angina/NSTEMI Renal Insufficiency Patient Comorbidities Protected PCI Patients Complex Coronary Artery Disease Multi-vessel Disease Distal Left Main Disease Complex Lesions (bifurcations, calcification) CTO Retrograde Hemodynamic Compromise Mild, Moderate, Severely Depressed Ejection Fraction High LVEDP Protected PCI with Impella FDA Indicated Safe & Effective for High Risk PCI
Symptoms Symptoms PATIENTS MOST APPROPRIATE FOR REVASCULARIZATION 7 Coronary Revascularization Appropriateness Guidelines ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT 1 Heart Failure Angina High Risk Findings on Noninvasive Study CCS Class III or IV Angina Symptoms Med. Rx Class III or IV Max Rx A A A A A Class I or II Max Rx A A A A A Asymptomatic Max Rx U A A A A Class III or IV No/min Rx A A A A A Class I or II No/min Rx U A A A A Asymptomatic No/min Rx U U A A A Coronary Anatomy CTO of 1 vz.; no other disease 1-2 vz. disease; no Prox. LAD 1 vz. disease of Prox. LAD 2 vz. disease with Prox. LAD 3 vz. disease; no Left Main Protected PCI Patients = More Heart Failure More Angina More Complex = More likely to be appropriate Stress Test Med. Rx High Risk Max Rx A A A A A High Risk No/min Rx A A A A A Int. Risk Max Rx A A A A A Int. Risk No/min Rx U U A A A Low Risk Max Rx U A A A A Low Risk No/min Rx I U A A A Coronary Anatomy CTO of 1-vz; no other disease 1-2-vz. disease; no prox. LAD 1-vz. disease of prox. LAD 2-vz. disease with prox. LAD 3-vz. disease; no left main A = Appropriate, U = Uncertain, I= Inappropriate Complexity A = Appropriate, U = Uncertain, I= Inappropriate Complexity 1. Patel MR, et al, J AM Coll Cardiol. 2012;59(9); 857-881
PATIENT CHARACTERISTICS OF HIGH RISK 8 REVASCULARIZATION STUDY SYNTAX 1 Stent vs. CABG (n=903) HIGH RISK PCI STUDY PROTECT II 2,3 Impella 2.5 vs. IABP (n=427) LVEF 35% (%) ~2 100 CHF (%) 4 87 Unstable Angina 29 40 Diabetes (%) 26 51 Prior MI (%) 32 68 Prior PCI 0 40 Prior CABG 0 34 Age (Mean±SD) 65±10 67±11 Not Surgical Candidates (%) 0 64 * * 64% of patients determined inoperable by surgical consult or refused surgery. Remaining 36% determined not surgical candidate by treating physician. 1.Serruys PW et al., N Engi J Med. 2009;360:961-972 2.Dangas et al., Am. Journ of Cardiol. 2014: 113(2):222-8 3.Pershad, et al., Am J Cardiol. 2014 Sep 1;114(5):657-64
Anatomic Risk REVASCULARIZATION STRATEGY BY RISK CATEGORY 9 Surgical Risk Low Medium High Often inoperable Low PCI PCI PCI Medium CABG or PCI PCI or CABG Support & PCI Protected PCI FDA Indicated Safe & Effective High CABG CABG or PCI Support & PCI ACC/AHA PCI Guidelines 1,2 SYNTAX Study 1. Levine GN, et al. J Am Coll Cardiol, 2011 Dec 6;58(24):e44-122, 2 Amsterdam EA, et al. Circulation. 2014 Dec 23; 130(25):e344-426
HEMODYNAMICS OF PROTECTED PCI 10 Case Example* 66 yo male 85% SVG Last patent conduit EF = 30% NYHA Class IV Prior CABG Prior PCI Hemodynamically stable Not Surgical Candidate MAP 110 mmhg MAP 86 mmhg Impella 2.5 On No Impella Simulated Arterial Pressure Tracings 1-8% -10% -12% 97 mmhg -15% -23% -51% 42 mmhg Case Balloon Start Inflation 1. Physiologic computational modeling, Am J Physiol 1991;260 (HCP 29): H146-H157 * Not all patients will experience the same clinical outcomes or hemodynamic responses 15 sec 30 sec 45 sec
IMPELLA SUPPORT INCREASES ARTERIAL PRESSURE 11 U.S. Impella Registry Data 1 N=148 Systolic Pressure 119±25 Pre- Impella p<0.0001 17% 139±27 On Impella Diastolic Pressure 64±15 Pre- Impella p<0.0001 26% 81±19 On Impella 83±18 Pre- Impella Mean Pressure p<0.0001 22% 101±20 On Impella 1. Maini et al,.catheter Cardiovasc Interv. 2012 Nov 1;80(5):717-25
IMPELLA DEVICES MAY IMPROVE CORONARY PERFUSION PRESSURE 1 12 Distal CPP* Effective CPP* LVEDP Diastolic Aortic Pressure (N=11) (N=11) (N=11) (N=11) 51.8 17% 60.8 49.8 35% 67.1 27 19% 72 60 22 20% (p<0.001) (p<0.001) (p<0.002) (p<0.001) P2 Flow P8 Flow P2 Flow P8 Flow P2 Flow P8 Flow P2 Flow P8 Flow Data from patients with critical coronary stenosis IABP has demonstrated no increase in CPP* distal to lesion 2 1. Alqarqaz, et.al. Circ Cardiovasc Interv. 2018;11:e005870. 2. Kern, et.al., Circulation 1993;87:500-511 *(CPP) Coronary Perfusion Pressure
HALF AS MANY HYPOTENSIVE EVENTS PER PATIENT WITH PROTECTED PCI 13 Hypotensive Events per Patient N = 421 0.96 p=0.001 53% Reduction 0.45 Protect II FDA PMA data Hypotensive event defined as MAP < 65mmHg IABP Impella FDA Randomized Controlled Trial Protect II
IMPELLA MAINTAINS PATIENT HEMODYNAMICS ALLOWING FOR MORE COMPLETE REVASCULARIZATION 14 Procedural Decrease in Arterial Pressure from Baseline IABP Impella N = 325 1 Vessel Treated 2 Vessels Treated 3 Vessels Treated -2.7% -8.5% -7.6% p <0.001 p =0.007 p =0.026 Baseline Protected PCI -13.1% -14.9% Kovacic, et al. J Interv Cardiol. 2015 Feb;28(1):32-40 -18.8% FDA Approved Randomized Controlled Trial Protect II
MORE COMPLETE REVASCULARIZATION LEADS TO REDUCED ADVERSE EVENTS 15 MACCE at 90 Days Protect II, Both IABP and Impella Arms, All Patients 33.8% p=0.019 23.3% 17.0% N=157 N=215 N=53 1 Vessel Treated 2 Vessels Treated 3 Vessels Treated O'Neill, PROTECT II Abstract, Presented at Transcatheter Cardiovascular Therapeutics 2013 FDA Approved Randomized Controlled Trial Protect II
MACCE (%) IMPELLA REDUCES PERI & POST PROCEDURAL MACCE 16 MACCE 30 25 20 MACCE = Death, Stroke, MI, Repeat revasc. IABP N=211 29% reduction In MACCE 15 Impella N=216 10 p=0.042 0 10 20 30 40 50 60 70 80 90 Time Post Procedure (day) Dangaset al, Am. Journ of Cardiol. 2014: 113(2):222-8 FDA Approved Randomized Controlled Trial Protect II
IMPELLA REDUCES MACCE WITH MORE COMPLETE REVASCULARIZATION 17 MACCE at 90 Days 35.0% p=0.747 32.5% 28.5% p=0.015 44% Reduction 15.9% IABP N=80 Impella N=77 IABP N=130 Impella N=130 1 Vessel Treated 2 or 3 Vessels Treated Protect II FDA PMA data ULM Included in 2 or 3 Vessels Protect II Study
COST EFFECTIVENESS OF PROTECTED PCI 18 Reduced Length of Stay Total Days in Hospital 1,3 Less Readmissions from Repeat Procedures 9.0 p=0.008 2 days or 22% 12.4% p=0.024 52% Reduction 7.0 6.0% N=211 N=216 N=211 N=216 IABP Impella IABP Impella Median days in hospital; index stay through 90 days, N=427, Readmissions N=208 1. Gregory, O Neill, et al. American Health & Drug Benefits 2013 Mar;6(2):88-99 2. Gregory, et al. Managed Care Medicine, Feb 2013 3. Maini, et al. Expert Rev Pharmacoecon Outcomes Res. 2014 Jun;14(3):403-16
HIGH RISK PATIENTS MAY BENEFIT FROM PROTECTED PCI LVEF Improvement Post Protected PCI 19 2 Italian Ctrs Study 1 (n=10) 41±13 Protect I 2 (n=16) 31±7 32% p=0.02 26±6 31% 34±11 p=0.003 Pre-PCI Follow-up Pre-PCI Follow-up U.S. Impella Registry 3 (n=175) 30±15 17% 35±15 p<0.0001 27±9 Protect II 4 (n=175) 22% 33±11 p<0.001 Pre-PCI Follow-up Pre-PCI Follow-up 1. Burzotta et al. Cardiovasc Med 2008 Oct;9(10):1004-10.; 2. Dixon et al. JACC Cardiovasc Interv. 2009 Feb;2(2):91-6; 3. Maini et al,.catheter Cardiovasc Interv. 2012 Nov 1;80(5):717-25.; 4.O Neill et al. Circulation. 2012 Oct 2:126(14):1717-27
IMPROVEMENT IN QUALITY OF LIFE POST PCI 20 NYHA Class Improvement Post Procedure p<0.001 17% 58% Reduction in Class III,IV 8% 18% Class IV 45% 30% Class III Class II 31% 44% Class I 7% Baseline 90 days N=223 patients from Both Arms of Protected II Trial with NYHA measurements available at baseline and 90 days 1 O Neill WW et al. Circulation. 2012 Oct 2:126(14):1717-27 FDA Approved Randomized Controlled Trial Protect II
IMPROVEMENT IN QUALITY OF LIFE POST PCI 21 LVEF Improvement Post Protected PCI NYHA Class Improvement Post Procedure Protect II (n=175) p<0.001 33±11 17% 58% Reduction in Class III,IV 8% 18% p<0.001 Class IV 22% 45% 30% Class III 27±9 Class II 31% 44% Class I Pre-PCI Follow-up 7% Baseline 90 days O Neill WW et al. Circulation. 2012 Oct 2:126(14):1717-27 IMP-1015-16 v.4 N=223 patients from Both Arms of Protected II Trial with NYHA measurements available at baseline and 90 days FDA Approved Randomized Controlled Trial Protect II
ADDITIONAL IMPELLA SAFETY ENDPOINTS 1 22 IABP Control Arm (n=210) Impella Protected PCI (n=215) p-value Aortic Valve Damage 0 0 NA Vascular Complications 2 1.9% 1.4% 0.680 Acute Renal Dysfunction 4.8% 4.2% 0.774 (Total Contrast media) 3 (241 ml) (267 ml) (0.036) 1. O Neill WW et al. Circulation. 2012 Oct 2:126(14):1717-27 2. Vascular complications from Protect II RCT = Cardiac, thoracic, or abdominal operation, or vascular operation for limb ischemia. 3. Acute renal dysfunction was numerically lower even with additional contrast media in the Protected PCI with Impella arm of Protect II RCT
CLINICAL GUIDELINES FOR IMPELLA 23 Protected PCI 2014 AHA/ACC Guideline for the Management of Patients With Non ST- Elevation Acute Coronary Syndromes. Circulation Revascularization in Heart Failure: Class I Revascularization strategy based on degree, severity, & extent of CAD; cardiac lesions; extent of LV dysfunction; prior revascularization. PVADS: Large amount of ischemic territory/poor LV function 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC High risk patients: Class IIb CLASS III: HARM without Hemodynamic support; for PCI at hospitals without on-site cardiac surgery Categories referencing Impella include Percutaneous LVAD, PVAD, Non-durable MCS, TCS and percutaneous MCSD Reimbursement and coding information: Inpatient Hospital = ICD.9 Code 37.68, commonly MS-DRG 216/217 Physician = CPT codes 33990 (insertion), 33992 (removal), 33993 (repositioning) Additional Guidelines 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC PCI and Cardiogenic Shock: Class I Use of Mechanical Circulatory Support: American Heart Association. Circulation 2012 Acutely decompensated heart failure patients: Class IIa 2013 Int l Society for Heart & Lung Transplantation Guidelines for Mechanical Circulatory Support. Jnl of Heart & Lung Transplantation Temporary mechanical support for patients with multi-organ failure: Class I 2013 ACCF/AHA Guideline for the Management of Heart Failure, JACC Bridge to Recovery or Bridge to Decision for patients with acute, profound hemodynamic compromise: Class IIa 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation STEMI and Cardiogenic Shock: Class IIb STEMI and urgent CABG: Class IIa
CONCLUSIONS 24 1. Candidates are hemodynamically stable, higher risk patients that have depressed LVEF, complex CAD, & co-morbidities 2. Higher risk patients are appropriate for revascularization according to AUC criteria; a heart team should determine PCI or CABG 3. Impella is the only hemodynamic support device proven safe and effective in elective and urgent High-Risk PCI patients 4. Benefits from a Protected PCI may include: More complete revascularization with reduction in MACCE Reduction in symptoms and class of heart failure Improvement in LVEF post procedure Reduction in days in the hospital Reduction in readmissions due to fewer repeat procedures 5. Clinical guidelines and the FDA approval support the use of Impella for Protected PCI in this higher risk patient population
INCOMPLETE REVASCULARIZATION IS COMMON 25 Incomplete Revasc Complete Revasc 69% 31% 42% 58% 46% 54% 43% 57% 37% 63% NY PCI 2003 ARTS I 1997 ARTS II 2003 SYNTAX PCI SYNTAX CABG
COMPLETE REVASCULARIZATION VS. INCOMPLETE 26 SYNTAX Study Farooq et al, JACC 2013 ACUITY Study Rosner G et al. Circulation 2012 41.9% 26.8% p<0.001 p<0.001 p<0.0001 p<0.0001 29.6% 15.7% 17.7% 10.2% 23.4% 16.6% Incomplete Complete Incomplete Complete Incomplete Complete Incomplete Complete All Cause Revasc MACCE All Cause Revasc MACE
META-ANALYSIS OF COMPLETE VS. INCOMPLETE REVASCULARIZATION 27 Pooled PCI Studies Relative Risk [95% CI] p-value Mortality 0.72 [0.64, 0.81] < 0.001 in patients with multivessel CAD undergoing revascularization with CABG or PCI, CR was associated with lower morbidity and mortality. MI 0.80 [0.71, 0.91] 0.001 Repeat Revasc 0.72 [0.63, 0.81] < 0.001 0.0 0.5 1.0 1.5 2.0 Complete revasc better Incomplete revasc better Garcia et al, JACC Vol. 62, No. 16, 2013
IMPELLA CP PUMP DATA SUBMITTED FOR PMA APPROVAL 28 Data from USPella (cvad) registry Analysis of consecutive, unselected patients Impella CP patients enrolled from Jan-Aug 2014 compared with patients submitted to FDA for Impella 2.5 Similar high-risk features of baseline risk. No significant differences in MACCE between patient groups Procedural and Support Characteristics Impella 2.5 (N= 637) Comparative data for patient cohorts Impella CP (N=72) p= Prevalence of CHF 52.80% 69.40% 0.008 Admitted for AMI 28.40% 38.90% 0.076 Recommeded for CABG 37.10% 21.10% 0.008 LM and/or LAD intervention 49.97% 56.80% 0.084 Treated with rotational atherectomy 16.70% 27.80% 0.032 Cause of Death Impella 2.5 (N= 637) Impella CP (N=72) Myocardial Infarction 1.26% (8) 2.78% (2) Decompensated Heart/Multi-organ failure 1.1% (7) 0 Procedural complication 0.31% (2) 0 Respiratory failure 0.16% (1) 0 Total 2.83% (18) 2.78% (2) Causes of in-hospital deaths for HRPCI patients supported with Impella 2.5 or Impella CP in Impella Registry. cvad Registry data submitted for FDA Approval
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