EECP EECP Enhanced External CounterpulsationEnhanced External Counterpulsation

EECP is a registered trademark of Vasomedical, Inc. © 1999 Vasomedical Inc.

A Medical Services Presentation from Vasomedical, Inc.

Symptomatic Coronary Artery DiseaseSymptomatic Coronary Artery DiseasePatient Distribution by Patient Distribution by AmenabilityAmenability to Treatments to Treatments

Medication and lifestyle modification

Surgical and/or percutaneous intervention (about 1.2 million patients per year)

Not readily amenable to intervention (80 - 200 thousand)

6.2 Million

The Weight of Clinical EvidenceThe Weight of Clinical Evidence

In most patients, EECP treatment...

• Reduces anginal pain

• Increases functional ability

• Improves quality of life

… both short-term and long-term

Target Population for EECP TherapyTarget Population for EECP Therapy

Coronary artery disease patients with angina pectoris refractory to medical therapy.

EECP Therapy Covered by MedicareEECP Therapy Covered by Medicare

For patients with a diagnosis of disabling angina pectoris who, in the opinion of their cardiologists or cardiac surgeons, are not readily amenable to invasive procedures because…

– They are inoperable or at high risk of operative complications or failure

– Their coronary anatomy is not readily accessible to such procedures

– Co-morbid states create excessive risk

Coronary HemodynamicsCoronary Hemodynamics

The EECP ProcedureThe EECP Procedure

Noninvasive procedure:

Produces:

Series of 3 cuffs wrapped around calves, lower thighs, upper thighs and buttocks

Sequential distal to proximal compression upon diastole, and Simultaneous release of pressure at end-diastole

Increased diastolic pressure and retrograde aortic flow

Increased venous return and...

Systolic unloading, resulting in increased cardiac output

Required Treatment RegimensRequired Treatment Regimens

• A total of 35 hours is required

• Regimen:1 or 2 hours daily

• At least 5 days per week for 4 to 7 weeks

It is recommended that 2 hours daily treatment sessions are separated by a 30 minutes rest interval.

Early external Early external counterpulsationcounterpulsationdevices had devices had hydraulic pulsator hydraulic pulsator chambers.chambers.

History of External CounterpulsationHistory of External Counterpulsation

1950’s1950’s: - Kantrowitz Brothers - diastolic augmentation- Sarnoff - LV unloading - Birtwell - combined concepts- Gorlin - defined counterpulsation

1960’s1960’s: - Birtwell & Soroff - Dennis- Osborne - hydraulic external counterpulsation

1970’s1970’s: - Soroff - cardiogenic shock- Banas - stable angina- Amsterdam - acute MI

1980’s1980’s: - Failure to gain acceptance- China; redeveloped technology- pneumatic system- Soroff, Hui, Zheng collaboration at Stony Brook

SUNY Stony Brook: The first publication - 1992SUNY Stony Brook: The first publication - 1992

Background: Of 18 patients with chronic angina refractory to medical therapy: - 8 had 19 prior revascularization attempts - 7 had 14 prior mycardial infarcts

Methods: 36 one-hour treatment sessions

Pre- and post-treatment thallium treadmill stress tests to

identical exercise times

Separate post-treatment maximal routine treadmill stress test

Results: All patients reported improvement in anginal symptoms:

- 16 patients (89%89%) reported no angina during usual activities:

- 12 patients (67%67%) with resolution of reversible perfusion defects

- 2 patients (11%11%) with improvement of reversible perfusion defects - 4 patients

(22%22%) with no change

Lawson WE, Hui JCK, Soroff HS, et al. Efficacy of enhanced external counterpulsation in the treatmentof angina pectoris. Am J Cardiol. 1992;70:859-862.

SUNY Stony Brook: SUNY Stony Brook: 3-year follow-up of the first 18 patients3-year follow-up of the first 18 patients

Background: Clinical follow-up of 18 initially treated patients was conducted after 3 years

Methods: Repeat stress thallium test performed to same exercise duration as initial study

Results: Of 14 patients who showed resolution/improvement in initial study:

- 11 patients remained free of limiting angina

- 1 patient was lost to follow-up and 1 refused another stress test

- 1 patient had surgical revascularization, 1 patient had an MI

Of the remaining 10 patients, 8 retained benefits and 2 reverted to pre- treatment baseline perfusion defects despite symptomatic benefit Lawson WE, Hui JCK, Zheng ZS, et al. Three year sustained benefit from enhanced external counterpulsation in chronic angina pectoris. Am J Cardiol. 1995;75:840-841.

SUNY Stony Brook: 5-year Follow-upSUNY Stony Brook: 5-year Follow-up

Background: A five-year follow-up was conducted on 33 angina patients treated between 1989 and 1992 with EECP, to assess morbidity and mortality.

Methods: Review of patient records at 5 years post-EECP (range 4-7 years).

Results: 29 of 33 patients remained alive. Of these, 9 patients were hospitalized (4 acute MI, 6 CABG/PTCA, 1 unstable angina and 1 other cardiac surgery).

Conclusions: Five-year survival without an interim event of 60% of patients treated with EECP appears similar to that seen

with comparable populations treated with CABG/PTCA.

Lawson WE, Hui JCK, Burger L, et al. Five-year follow-up of morbidity and mortality in 33 angina patient treated with enhanced external counterpulsation. J Invest Med. 1997;45:212A.

SUNY Stony Brook: Patient Response StudiesSUNY Stony Brook: Patient Response Studies

Results: In sixty patients with CAD, after EECP treatment, improvement or resolution of reversible radionuclide perfusion defects were seen in:

86%86% (18/21) of patients with residual 1-vessel disease

85%85% (17/20) of patients with residual 2-vessel disease

53%53% (10/19) of patients with residual 3-vessel disease

75%75% (45/60) of patients overall

Conclusion: A proximally patent conduit may be necessary to allow transmission of augmented diastolic pressure and flow to distal coronary circulation.

Lawson WE, Hui JCK, Tong G et al. Prior Revascularization Increases the Effectiveness of enhanced external counterpulsation? Clin. Cardiol. 1998; 21:841-844.

Effect of EECP Treatment on Exercise-Induced Effect of EECP Treatment on Exercise-Induced Radionuclide Defects in Fifty Consecutive Patients at Radionuclide Defects in Fifty Consecutive Patients at

SUNY Stony BrookSUNY Stony Brook

58

22 20

0

10

20

30

40

50

60

Percent of Patients

Resolved

Partial

No Effect

Lawson WE, Hui JCK, Zheng SZ et al. Can Angiographic Findings Predict Which Coronary Patients Will Benefit from Enhanced External Counterpulsation? Am J Cardiol 1996;77:1107-09

Results of The Multicenter Study of Enhanced Results of The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP): External Counterpulsation (MUST-EECP):

EECP Reduces Time to ST-Segment Depression EECP Reduces Time to ST-Segment Depression and Episodes of Angina with Improved and Episodes of Angina with Improved

Long-term Quality of LifeLong-term Quality of Life

Rohit R. Arora, MD; Tony Chou, MD; Diwakar Jain, MD; Richard Nesto, MD; Bruce Fleishman, MD;

Lawrence Crawford, MD and Thomas McKiernan, MDfor the MUST-EECP Investigators

MUST-EECP: Study SitesMUST-EECP: Study Sites

Columbia Presbyterian Medical Center Rohit Arora, MD

University of California San Francisco Tony Chou, MD

Yale University School of Medicine Diwakar Jain, MD

Beth Israel Deaconess Medical Center Richard Nesto, MD

Grant/Riverside Methodist Hospitals Bruce Fleishman, MD

University of Pittsburgh Medical Center Lawrence Crawford, MD

Loyola University Medical Center Thomas McKiernan, MD

MUST-EECP: Study GoalsMUST-EECP: Study Goals

• To confirm efficacy and safety of EECP using rigorous scientific method, i.e. a randomized, sham-controlled, double-blinded protocol generally reserved for drug trials

• To broaden study experience beyond initial trial site

• To determine effect vs. placebo

MUST-EECP: MethodMUST-EECP: Method

Design: Multicenter, randomized, sham-controlled, double-blinded trial

Randomization: Even assignment to EECP group or sham group in blocks of 10

allocated to each center

Subjects: 139 patients with chronic stable angina pectoris (137 evaluable )

Duration: May 1995 - July 1997

MUST-EECP: Pre-specified ParametersMUST-EECP: Pre-specified Parameters

Evaluate effect of EECP on... Measured by…

Exercise ability Exercise durationTime to ST-segment depression

Clinical status Frequency of anginal episodesIntake of nitroglycerin

Adverse experiences Physical examsLab tests Daily questions

Statistical analysis P-values calculated for between-group differences using Cochran-Mantel-Haenszel Chi-Squared tests for ordered categories stratified by investigator

MUST-EECP: Inclusion CriteriaMUST-EECP: Inclusion Criteria

Written informed consent

21-81 years of age

Canadian Cardiovascular Society Class I, II, or III

Evidence of CAD by one of following criteria:

Angiographic Angiographic (1 or more major arteries with >70% stenosis) or(1 or more major arteries with >70% stenosis) or

Documented evidence of MI orDocumented evidence of MI or

Positive nuclear stress test, plus... Positive nuclear stress test, plus...

A positive exercise stress test within 4-week baseline period

MUST-EECP: Exclusion CriteriaMUST-EECP: Exclusion Criteria

Pregnant or childbearing potential without contraception

Unstable angina

MI and/or CABG in prior 3 months

Cardiac catheterization in prior 2 weeks

Arrhythmias (AF or VPBs) interfering with triggering of EECP

Marked baseline ECG abnormalities limiting interpretation (digoxin use, LVH with strain, LBBB)

Permanent pacemaker or defibrillator

CHF (LVEF <30%)

Significant valvular heart disease

Severe symptomatic peripheral vascular disease

History of varicosities, deep vein thrombosis, phlebitis and/or stasis ulcer

ABP > 180/100 mm Hg

Bleeding diathesis; Coumadin use with INR >2.0

Inability to undergo treadmill tests

Non-bypassed left main with >50%

Inability to consent and/or cooperate throughout study duration

Enrollment in cardiac rehab. program

Participation in other research study

CCS class

I 26.826.8 25.825.8

II 49.349.3 51.551.5

III 23.923.9 22.722.7

Years of angina (±SD) 8.6 ± 7.98.6 ± 7.9 4.1 ± 4.54.1 ± 4.5 p <0.01

Previous MI 56.356.3 40.940.9 p <0.05

Previous CABG 46.546.5 37.937.9

Previous PTCA 38.038.0 33.333.3

MUST-EECP: CV Morbidity ProfilesMUST-EECP: CV Morbidity Profiles

% Active% Active %Sham%Sham (n = 71) (n = 66)

CV history:

MUST-EECP:Exercise ResultsMUST-EECP:Exercise Results

37-4

4226

-10 0 10 20 30 40 50

Time to STDepression

ExerciseDuration

Active Sham

Seconds

Adjusted mean of change from baseline

p = ns

p = 0.01

}

}

MUST-EECP: Percentage Change in Angina Counts MUST-EECP: Percentage Change in Angina Counts

0

20

0

50

0 10 20 30 40 50

Per ProtocolPer Protocol

P < 0.05

P < 0.02

Intent-to-treatIntent-to-treat

% Change

ActiveActive (N=57)

ShamSham (N=59)

ActiveActive (N=71)

ShamSham (N=66)

}

}

MUST-EECP: Percentage Change in MUST-EECP: Percentage Change in On-demand Nitroglycerin On-demand Nitroglycerin

0

0

0

0

0 0.2 0.4 0.6 0.8 1

Per ProtocolPer Protocol

P > 0.7

P > 0.9

Intent-to-treatIntent-to-treat

% Change

ActiveActive (N=57)

ShamSham (N=59)

ActiveActive (N=71)

ShamSham (N=66)

}

}

MUST-EECP: Adverse ExperiencesMUST-EECP: Adverse ExperiencesConsidered by investigators to be probably, possibly or definitely device related:

ShamSham ActiveActive (n=66) (n=71)

Paresthesia 11 2 2Edema, swelling 00 22Skin abrasion, bruise, blister 22 1313Pain in legs or back 77 2020Total 1010 3737

No. of patients reporting AE 1717 (25.8%) 3939 (54.9%)

Withdrew because of AE’s 11 77

P = 0.005

P = 0.01

P < 0.001

P < 0.001

Summary of Clinical ResultsSummary of Clinical Results

Compared to sham, EECP: Increased time to exercise-induced ST segment depression (p=

0.01)

Decreased the frequency of angina episodes (p< 0.04)

Compared to baseline: Exercise duration increased significantly in both groups

(Sham- p<0.03, Active- p< 0.001) Time to ST segment depression increased significantly in Active

Group only (p< 0.002)

EECP was generally well tolerated but with significantly fewer adverse experiences reported in the sham group.

International EECP Patient Registry International EECP Patient Registry (Department of Epidemiology, University of Pittsburgh School of Public Health)

Before treatment, the first 1213 consecutive patients…

• 74%74% had Functional Class III or IV disease (With a mean of 9 angina episodes per week before treatment)

• 78%78% have multi-vessel disease

• 81%81% had prior CABG or PTCA

• 66%66% were not eligible for CABG or PTCA

• 64%64% had a prior MI

• 39%39% have diabetes

International EECP Patient Registry CCS International EECP Patient Registry CCS Classes Pre- & Post- Treatment (N=1213)Classes Pre- & Post- Treatment (N=1213)

0

100

200

300

400

500

600

None I II III IV

Pre-TxPost-Tx

Patients

CCS Classes

The Weight of Clinical Evidence: SummaryThe Weight of Clinical Evidence: Summary

• EECP is a safe and effective treatment for angina EECP is a safe and effective treatment for angina pectoris refractory to medical therapypectoris refractory to medical therapy

• Benefits of EECP include an improvement of Benefits of EECP include an improvement of functional status in more than 70% of patientsfunctional status in more than 70% of patients

• Benefits accrue both short-term and long-termBenefits accrue both short-term and long-term

EECPEECP

Enhanced External CounterpulsationEnhanced External Counterpulsation