Results of Clinical Trials

Transcription

1 Results of Clinical Trials

2 21 patients (14 Class* IV, 6 Class III, 1 Class II) ECP given 1 hour daily, for 5 days 18 of 21 had significant diastolic augmentation (75.3 ± 1.8 vs ± 2.7 mmhg) 17 of 18 free of pain by day four One month later, 10 patients were Class I, 8 Class II Angiograms in 5 of 11 patients showed definite increase in vascularity * CCSC = Canadian Cardiovascular Society (Angina) Class Banas JS et al. Am J Cardiol 1973;31:116

3 Background: 18 patients with chronic angina refractory to medical therapy 8 had 19 prior revascularization attempts 7 had 14 prior myocardial infarctions Methods: 36 one-hour treatment sessions Pre- and post-eecp thallium stress tests to same exercise times Separate, post-treatment maximal routine treadmill stress test Results: 18 patients (100%) reported improvement in anginal symptoms 16 patients (89%) with no angina during usual activities 12 patients (67%) with resolution of reversible perfusion defects* 2 patients (11%) with improvement of reversible perfusion defects* 4 patients (22%) with no change in stress perfusion defects* * Thallium-201 stress testing performed Lawson WE, Hui JCK, Soroff HS, et al. Am J Cardiol 1992;70:

4 Exercise duration, mean (min) P<0.005 Pre-EECP Post-EECP Lawson WE, Hui JCK, Soroff HS, et al. Am J Cardiol 1992;70:

5 Pre-EECP Stress Rest Post-EECP Stress Rest Lawson WE, Hui JCK, et al. J Crit Illness 2000;15(11):629-36

6 Percent of patients Improved reversible perfusion defects Resolution of reversible perfusion defects Improved or resolved Perfusion defects Lawson WE, Hui JCK, et al. Am J Cardiol 1992;70:

7 Pre-EECP Post-EECP 3-Year Follow-up Initial 18 patients positive for reversible defects (RD) 4 patients positive RD 3 patients with partial improvement 11 patients with no RD 2 patients unchanged 2 patients with events* 8 patients unchanged 2 patients with RD 2 patients lost/refused 2 patients with events* * Events = CABG, PTCA, MI Lawson WE, Hui JCK, et al. Am J Cardiol 1995;75:

8 Non-randomized observational studies of angina pectoris with ETT (some radionuclide), NTG use, CCS angina Class and HQOL measures: Dresden and Erlangen, Germany Howard County General Hospital, Columbia,MD Beaumont Hospital, Dublin, Ireland Hammersmith Hospital, London, England Mayo Clinic, Rochester, MN Kyoto and Kurume, Japan Grant Hospital, Columbus, OH and Port Chester, NY Study results consistent with Stony Brook findings

9 EECP TREATMENT Before (156 segments) After (156 segments) P value Normal perfusion imaging 78 (50%) 104 (67%) p<0.01 Abnormal perfusion imaging 78 (50%) 52 (33%) P<0.01 Fixed perfusion defects 24 (15%) 20 (13%) P=NS Reversible perfusion defects 54 (35%) 32 (21%) P<0.01 Urano H, et al. J Am Coll Cardiol 2001;37:93-99

10 Exercise duration (sec) P<0.05 P<0.05 Time to 1 mm ST depression (sec) P<0.05 P<0.05 Urano H et al J Am Coll Cardiol 2001;37:93-99

11 Double product (mmhg x bpm) Time to I mm ST depression (sec) Pre-EECP Post-EECP Exercise time (sec) Pre-EECP Post-EECP Masuda D, et al. Eur Heart J 2001;22(16):

12 Stress myocardial perfusion (ml/min/g) p=0.02 Masuda D, et al. Eur Heart J 2001;22(16):

13 Journal of the American College of Cardiology Vol. 33, No. 7, 1999 Rohit R. Arora, MD, Tony M. Chou, MD, Diwakar Jain, MD, Bruce Fleishman, MD Lawrence Crawford, MD, Thomas McKiernan, MD Richard W. Nesto, MD for the MUST-EECP Investigators New York, New York; San Francisco, California; New Haven, Connecticut; Columbus, Ohio: Pittsburgh, Pennsylvania; Maywood, Illinois: Boston, Massachusetts

14 To confirm efficacy and safety of EECP using rigorous scientific method* To broaden study experience beyond earlier trials To determine effect versus placebo * i.e. randomized, sham-controlled, double-blind protocol MUST-EECP Arora RR, et al. J Am Coll Cardiol 1999;33:

15 p > 0.3 p = 0.01 Time (Seconds) Exercise Duration Time to ST Depression * Adjusted mean of change from baseline MUST-EECP Arora RR, et al. J Am Coll Cardiol 1999;33:

16 } P < 0.02 } P < 0.05 % Change MUST-EECP Arora RR, et al. J Am Coll Cardiol 1999;33:

17 } P > 0.9 } P > 0.7 % Change MUST-EECP Arora RR, et al. J Am Coll Cardiol 1999;33:

18 Sham (n=66) EECP (n=71) P Value Paresthesia 1 2 p>0.5 Edema 0 2 p=0.5 Skin abrasion, bruise, blister 2 13 p=0.005 Pain in leg or back 7 20 p=0.01 Total p<0.001 # Patients reporting AEs 17 (25.8%) 39 (54.9%) p<0.001 Withdrawal due to AE 1 7 * Considered by investigator as probably, possibly or definitely device related MUST-EECP Arora RR, et al. J Am Coll Cardiol 1999;33:

19 Enrolled 3,788 patients Analyzed 2,289 consecutive patients Over 100 centers including university medical centers, hospitals, clinics, physicians offices and rehabilitation centers Patients with chronic angina (Class* I-IV) * Canadian Cardiovascular Society (Angina) Class Lawson W, Hui J, Lang G. Cardiology 2000;94:31-35

20 * Patients improved after EECP treatment (%) * Canadian Cardiovascular Society (Angina) Class Lawson W, Hui J, Lang G. Cardiology 2000;94:31-35

21 Journal of Investigative Medicine Vol. 50, No. 1, 2002 Rohit R. Arora, MD, Tony M. Chou, MD, Diwakar Jain, MD, Bruce Fleishman, MD Lawrence Crawford, MD, Thomas McKiernan, MD Richard W. Nesto, MD for the MUST-EECP Investigators New York, New York; San Francisco, California; New Haven, Connecticut; Columbus, Ohio: Pittsburgh, Pennsylvania; Maywood, Illinois: Boston, Massachusetts

22 Physical Functioning (Work) Role Disability Due to Physical Health Bodily Pain General Health Vitality Social Functioning St. Sig. Within Group Difference St. Sig. Between Group Difference (Work) Role Disability Due to Emotional Health Mental Health Cardiac Specific Health & Functioning Magnitude of Improvement or Decline Expressed in Standard Deviation Units

23 Organized in 1998 to document patterns of use, safety and efficacy of EECP in consecutive series of patients Open to all centers using EECP for treatment of angina pectoris Voluntary registry (no payment to patients or centers) Phase 1 planned to enroll 5000 consecutive patients with follow-up for minimum of three years Data on File: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh

24 92 Centers 82 United States 5 Europe 5 Other international 5222 patients in current enrollment 5718 courses of EECP therapy Data on File: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh

25 Age: 66 ± 11 Male/Female ratio: 74/26 Time since diagnosis: 9 years Multivessel CAD: 78% Prior PCI: 60% Prior PCI/CABG: 80% Prior MI: 64% Prior CHF: 27% Data on File:Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh

26 67.5% 13.8% 16.5% 15.9% Percent of total N=597 N=562 N=536 N=380 Totals Data on File:Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh

27 Data on File:Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh

28 Data on File:Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh

29 Only one randomized study and with no pure placebo Mechanism of benefit is unclear Need better means of identifying which patients benefit the most No studies of repeat EECP nor extended treatment; need for, and benefit uncertain

30 Consistent reduction in anginal episodes Sustained improvement in CCS Angina Class Increased time to ST-segment depression; greater exercise work-load (METS) Fewer stress-induced reversible perfusion defects Better health-related quality of life

31 Results of Clinical Trials End