Conflict of Interest Slide

Transcription

1 Comparison of six- month clinical outcomes, event free survival rates of patients undergoing enhanced external counterpulsation (EECP) for coronary artery disease in the United States and Europe Ozlem Soran, MD, FACC, FESC, Elizabeth D. Kennard, PhD *, MD *, Sherly F.Kelsey *, PhD, on be half of IEPR Investigators Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA, Department of Epidemiology*, University of Pittsburgh, Pittsburgh, PA, USA

2 Conflict of Interest Slide Present: NONE Past: Vasomedical Inc.; speaker's bureau

3 Introduction EECP is a novel, non-invasive analogue of the intraaortic balloon pump. Use of EECP as a treatment for coronary artery disease has steadily increased in the past 7 years. Clinical studies consistently show that this novel pneumatic technology provides beneficial effects in 70-80% of enrolled patients. Although primarily used in the United States (US) the treatment is now also being used in Europe (EU).

4

5 Postulated Mechanisms of Action Hemodynamic Effects of EECP Increase Cardiac Output Increase coronary Perfusion Improve Diastolic Filling Diastolic Augmentation Pressure Gradients Increase Venous return Systolic unloading Diastolic Retrograde Flow occlusion Remodeling Enhance Collateral capillary sprouting Increase Shear Stress on endothelium Neurohormonal Release Increases: NO, ANP Deceases: BNP, ET-1, ACE, ANG II Improve Endothelial Function Release of Growth Factors Angiogenesis and Arteriogenesis

6 EECP Hemodynamic Effects Increased Venous Return Diastolic Augmentation Control Counterpulsating Improve LV Diastolic Filling Systolic Unloading Finger Plethysmograph Duplex echocardiography of the descending aorta

7 mmhg Aortic and Intracoronary Pressure during Enhanced External Counterpulsation Diastole Systole 0 Michaels AD, et al. Circulation 2002; 106:

8 Current Status of EECP FDA approved indications Treatment of patients with 1.Congestive heart failure 2.Stable or unstable angina pectoris 3.Acute myocardial infarction 4. Cardiogenic shock.

9 Aim Most of the EECP Therapy related studies have been conducted in a placebo controlled randomized or a non randomized fashion. Since the clinical trials assess the treatments in well controlled circumstances, the International EECP patient registry (IEPR) was initiated at the University of Pittsburgh to assess effectiveness of the system in the real world settings without applying inclusion and exclusion criteria. The aim of this study is to compare the clinical outcomes, repeat EECP and 6-months major adverse cardiovascular events (MACE: Death/CABG/PCI/MI) free survival rates for patients treated with EECP for coronary artery disease in EU with the US.

10 Methods coordinated at the University of Pittsburgh; patients enrolled from 90 centers; 4658 were treated and followed in the US and 262 in EU. Comparisons between groups were analyzed using chi-square tests for categorical parameters and t-tests for continuous variables. Rates of follow-up events were analyzed using survival methods. Angina status and major adverse cardiac events (MACE) were assessed. MACE were defined as the composite of death, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting.

11 Demographics US Sites N=4658 EU Sites N=262 Mean age (p<0.001) Male gender (p<0.001) 67 years 64 years 73% 87%

12 Medical History US Sites N=4658 EU Sites N=262 Previous revascularization p<0.001 Not revascularizable P=0.003 Heart failure p=ns Prior MI p=ns 89% 80% 87% 81% 31% 33% 71% 67%

13 Coronary Disease US Sites N=4658 EU Sites N=262 No Angina 0% 0% Severe Angina p<0.001 Multivessel disease p<0.05 Nitroglycerin Usage / week p< % 48% 91% 83% 9.9 ± ±14.1

14 Risk Factors Diabetes p<0.001 Hypertension p<0.001 Hyperlipidemia p<0.001 Smoking History Past Present US Sites N=4658 EU Sites N=262 44% 26% 76% 42% 86% 65% 61% 68% 8% 7%

15 EECP Therapy Mean treatment hours p<0.001 Diastolic augmentation First hour peak p<0.001 Diastolic augmentation Last hour peak P<0.001 US Sites N=4658 EU Sites N= ± ± ± ± ± ±0.68

16 Post-EECP outcome MACE (Death/MI/CABG/ PCI) p=ns US Sites N=4658 EU Sites N= % 1.6% No Angina 16% 33% Angina down by 1 class (%) p=ns Discontinued nitro use p=ns 76% 78% 54% 51%

17 6 Months Follow up- Results US Sites N=4658 EU Sites N=262 No angina 25% 25% Maintained the improvement in Angina Class p< % 66%

18 6 Months Follow up- Results US Sites N=4658 EU Sites N=262 Survival rate p=ns MACE free survival rate p=ns Repeat EECP rates p< % 98% 90% 92% 4% 0.5%

19 CONCLUSIONS Patients presenting for EECP treatment from EU and US populations show very different baseline profiles. However, both cohorts achieved substantial reduction in angina with high event free survival rates at 6 months. For patients with refractory angina pectoris the best treatment options have not been fully defined. EECP may offer a safe and effective treatment option for this group of patients.

20 Collateral Development in Experimental Heart (Dog) Following Counterpulsation Before After Jacobey JA, Taylor WJ, et al. Am J Cardiol

21 Increase (%) EECP: Change in Angiogenic Factors HGF bfgf VEGF MCP-1 Masuda D, et al. Circulation

22 Effects of EECP on Arteriogenesis CFI = ±0.07 (Sham) ± 0.07 (Active) p= p= p=0.04 CFI Sham-ECP Active-ECP Baseline Post-ECP Mean Coronary Occlusive Pressure -Central Venous Pressure Collateral flow index (CFI) = Mean Aortic Pressure -Central Venous Pressure Gloekler S et al; Heart 2010

23 EECP improves endothelial function Enhanced External Counterpulsation Treatment Improves Arterial Wall Properties and Wave Reflection Characteristics in Patients With Refractory Angina J Am Coll Cardiol, 2006; 48:

24 Effects of EECP on Peripheral Endothelial Function Control (Sham) EECP (n=10) Active EECP (n=20) Parameters Baseline Post p Baseline Post- p Sham EECP BFMD (%) NS <0.05 FFMD (%) NS <0.05 FBF (ml/min/100ml) NS <0.05 CBF (ml/min/100ml) NS <0.05 Ala (%) NS <0.05 T p (ms) NS <0.05 LV we (msec-mm Hg -2 ) NS <0.05 CF-PWV (m/sec) NS <0.05 Plasma Nox ( mol/l) NS <0.05 ADMA ( mol/l) NS <0.05 ED (sec) NS <0.05 Time to angina (sec) NS <0.05 VO 2peak (ml/kg/min) NS <0.05 Braith: 58 Annual Scientific Session ACC Orlando, 2009

25 Pressure Wave Travel Time (msec ) Augmentation Index (%) Effects of EECP on Pulse Wave Velocity and Arterial Stiffness Travel Time of Reflected Wave Decreased PWV Increased t p / 2 Arterial Stiffness Arterial Stiffness Augmentation Index 74 p= % p= % Pre-EECP Post-EECP 0 Pre-EECP Post-EECP Ps Pi Pulse Pressure = ( Pi Pd ) Augmentation Index = (Ps Pi) / (Ps Pd) Pressure without reflection Time for pressure wave to travel from aortic root and back = t p Wasted LV pressure energy = 2.09 X tp * (Ps Pi) Pd LV Workload = Tension Time Index = area under systolic wave J Am Coll Cardiol 2006;48:

26 Intima/media area ratio magnification 40 50µm magnification µm Effects of EECP on Intimal Hyperplasia Left Anterior Descending Coronary Artery 50µm * 50µm Control CHOL CHOL+ EECP N=7 N=11 N=17 CHOL group fed with high cholesterol atherogenic diet for 15 weeks EECP started at 7½ wks, treated for 7 ½ wks Intimal Area = (Internal elastic laminal lumen area) 0 Control CHOL CHOL + EECP There was no significant difference between Control and CHOL+EECP * p<0.05 for CHOL vs Control p <0.05 for CHOL+EECP vs CHOL Media Area = (External elastic laminal internal elastic laminal) Circulation 2007;116:

27 Review of the Mechanisms of Action of EECP Therapy Acute Effects during EECP treatment as a Circulatory Assisted Device Workload of the heart Coronary blood flow Systemic circulation Improve Endothelial Functions Nitric oxide Endothelin Intimal hyperplasia Arterial stiffness Improve Ischemic Heart Disease & Heart Failure Exercise Capacity Quality of Life Medications Coronary collateral flow Ejection Fraction Functional Class Neurohormonal Deactivation Angiotension, ANP, BNP Reduce Proinflammatory Cytokines TNF-, MCP-1 Regulates smooth muscle tone cgmp