Medicine Section - Enhanced External Counterpulsation (EECP) for Chronic Stable Angina or Congestive Heart Failure

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

DESCRIPTION

Enhanced external counterpulsation (EECP) is a noninvasive, adjunct treatment that uses timed, sequential inflation of pressure cuffs on the legs and is primarily investigated as a treatment for chronic stable angina and congestive heart failure (CHF). Treatment is usually administered in 1- to 2-hour sessions, 5 days a week for 7 weeks, for a total of 35 hours of treatment.

A number of EECP devices have received 510(k) approval from the U.S. Food and Drug Administration (FDA).

POLICY/CRITERIA

Enhanced external counterpulsation is considered investigational for the treatment of all cardiac conditions, including but not limited to chronic stable angina pectoris and congestive heart failure.

POSITION SUMMARY

The evidence is not sufficient to permit conclusions about the benefits of EECP in the treatment of chronic stable angina or CHF:

• There is no reliable, long-term evidence from well-designed, randomized controlled trials on the effectiveness of EECP in the treatment of stable angina pectoris and CHF.
• It is uncertain whether true EECP offers any additional benefit compared to the sham treatment. In addition, it is uncertain whether EECP is as effective as the standard treatment options currently available to patients with chronic stable angina or CHF, including pharmacotherapy, exercise, or more invasive procedures such as percutaneous coronary intervention (PCI).

Effectiveness:

Chronic Stable Angina

Randomized Controlled Trials (RCT)

Only two randomized controlled trials evaluated the effectiveness of EECP in the treatment of stable angina pectoris. (1, 4, 5)

Randomized, double-blinded Multicenter Study of Enhanced External Counterpulsation (MUST-EECP) compared active EECP to sham treatment in 139 patients with stable angina. (1-4) The study describes changes in the following measures:

• Changes in frequency of angina episodes and nitroglycerin (NTG) use
• Changes in exercise treadmill test (ETT) as measured by exercise duration and time to ≥1-mm ST-segment depression

Only the time to ST-segment depression changed significantly from baseline in the active EECP treatment group compared with the sham-treatment group, but the clinical significance of this 37-second improvement is unknown. In addition, several design flaws undermine the validity of the study findings:

• The sample size was too small to permit subset analyses, such as comparison of patients with different disease severity or different angina-related medical history.
• The active and sham treatment groups were significantly different at baseline, with longer angina duration, a higher proportion of patients with myocardial infarction (MI), and more residual vessel disease in the active EECP group, suggesting there may be a difference affecting the outcome.
• Patients were not followed-up beyond the 35-session treatment period that lasted up to 7 weeks, limiting conclusions on the durability of treatment effects.
• EECP was studied as an adjunct to pharmacotherapy. The participants self-reported the NTG use throughout the study. The recall bias in reporting of medication use may confound study findings.
• There was a large overall and differential loss to follow-up. Exercise duration data were only available for 87% and 79% of the patients in the sham and EECP groups respectively, potentially undermining randomization and comparability of treatment groups. Consequently, the treatment responses observed could have been confounded by differences in demographic, clinical or other characteristics between the groups.
• Intention-to-treat (ITT) analyses were reported only for the two outcomes of interest, angina count and nitroglycerin use.
• It is also noted that considerable exclusion criteria, such as exclusion of patients with Canadian Cardiovascular Society (CCS) class IV angina, limit the generalizability of study findings to all angina patients seen in clinical practice.
• A 12-month MUST-EECP follow-up study describes the effects of EECP on the patients’ functioning and sense of well-being as measured by the Health-Related Quality of Life (HQOL) scale. (2-4) Although improvement in several quality of life scales were reported for the EECP-treated patients, only 71 (54%) of the original 139 subjects were included in this study. The findings from this follow-up could not be correlated to the treatment responses reported in the first study due to data limitations.

The second RCT examined the effect of EECP on the circulatory levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris (5). Although the study findings suggest an anti-inflammatory effect, the clinical significance of the observed effect is unclear. Furthermore, the study findings are limited by the very small sample size (n=21), concurrent medication use, and lack of follow-up beyond treatment period.

Clinical Practice Guidelines (Chronic Stable Angina)

CHF

Randomized Controlled Trials

Only one randomized controlled trial examined the effects of EECP in the treatment of CHF. (8, 9, 2, 3) The Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart Failure (PEECH) study randomized 187 patients with mild or moderate heart failure to receive either EECP treatment in addition to optimal pharmacotherapy, or pharmacotherapy alone. The study evaluated changes in:

• Exercise duration (% patients with increase ≥60 seconds on treadmill, absolute change (seconds))
• Peak volume of oxygen uptake (Vo2) (% patients with increase ≥1.25 ml/min/kg)
• Quality of life measures (SF-36 and Minnesota Living with Heart Failure Questionnaire)
• New York Heart Association (NYHA) functional classification status 

Although the study reports improved exercise tolerance and NYHA functional classification in EECP-treated patients, several design flaws undermine the reliability of the study findings:

• The loss to follow-up was disproportionately large for the EECP compared to the control group (27% and 13.8% respectively), suggesting that there may be a difference that affects the outcome.
• Due to the nature of the comparison treatment, the patients undergoing EECP could not be blinded, increasing likelihood of the placebo effect.
• The randomization scheme was not explained. Inadequate randomization may result in unequal distribution of potential confounders, undermining the validity of study findings.
• The short follow-up period (6 months) limits conclusions regarding the durability of treatment effects.
• It is noted that substantial exclusion criteria, such as exclusion of NYHA functional class III and IV, limit the generalizability of study findings to the general population of patients with heart failure who are seen in clinical practice

In addition, the clinical significance of the ≥ 60s exercise duration increase is not clear. Finally, the magnitude of increase in NYHA classification was not reported, only the percent of patients with an increase.

Subsequent analysis of the PEECH participants over 65 years of age demonstrated statistically significant changes of both exercise duration and peak oxygen consumption. (10) Again, the clinical significance of these findings is not clear. In addition, the study was not sufficiently powered for this type of sub-analysis.

Clinical Practice Guidelines (CHF)

The 2005 ACC/AHA evidence-based practice guidelines update for the management of congestive heart failure in the adult states that “until more data are available, routine use of this therapy cannot be recommended for the management of patients with symptomatic reduced left ventricular ejection fraction (LVEF).” (11) The 2009 update does not include any changes regarding the use of EECP in CHF management. (12)

Other Comparative Studies, Case Series, and Multicenter Registry Studies of Angina and CHD

A number of non-randomized studies described experiences of EECP-treated angina and CHD patients. While these studies contribute to the body of EECP knowledge by informing hypothesis formulation, evidence from these studies is unreliable due to their inherent design flaws, such as non-random allocation of treatment, non-blind study design, and lack of non-EECP treated comparison groups. (13-29)

Safety:

There are no data on the long-term safety of EECP.  A number of adverse events have been noted during the treatment period; however, the literature does not report with certainty the extent to which some of these events are directly related to the EECP treatment itself:

1. Blisters
2. Bruising
3. Chest pain
4. Death
5. Deep vein thrombosis
6. Dysrhythmia
7. Edema
8. Exacerbation of CHF
9. Gastrointestinal Problems
10. Hemorrhoid complications
11. Myocardial infarction
12. Myocardial ischemia
13. Numbness
14. Pain (back or lower extremities)
15. Pulmonary embolism
16. Skin abrasion
17. Worsening angina

References

1. Arora RR, Chou TM, Jain D et al. The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol 1999;33(7):1833-40
2. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 2.02.06
3. BlueCross BlueShield Association Technology Evaluation Center : TEC Assessment: External Counterpulsation for Treatment of Chronic Stable Angina Pectoris and Chronic Heart Failure, 2005; vol 20 (tab 12)
4. Arora RR, Chou TM, Jain D et al. Effects of enhanced external counterpulsation on health-related quality of life continue 12 months after treatment: a substudy of the Multicenter Study of Enhanced External Counterpulsation. J Investig Med 2002;50(1):25-32
5. Casey DP, Conti CR, et al. Effect of Enhanced External Counterpulsation on Inflammatory Cytokines and Adhesion Molecules in Patients with Angina Pectoris and Angiographic Coronary Artery Disease. American Journal of Cardiology 2007; 300-2
6. Gibbons RJ, Antman EM, Alpert JS et al.  ACC/AHA 2002 guideline update for the management of patients with chronic stable angina.  A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines  (Committee to update the 1999 guidelines for the management of patients with chronic stable angina).  (Verified 07/13/08)
7. Fraker TD, Fihn SD et al. ACC/AHA 2007 Guideline Update for the Management of Patients with Chronic Stable Angina.  A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines Writing Group to Develop the Focused Update of the 2002 Guidelines for the Management of Patients with Chronic Stable Angina. http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.187930 (verified 07/13/09)
8. Feldman AM, Silver MA, Francis GS et al.  Treating heart failure with enhanced external counterpulsation (EECP): design of the prospective evaluation of EECP in heart failure (PEECH) trial.  J Card Fail  2005;11(3):240-5
9. Feldman AM, Silver MA, Francis GS et al. Enhanced external counterpulsation improves exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol 2006;48(6):1198-205
10. Abbottsmith CW, Chung ES, Varricchione T, et al. Enhanced external counterpulsation improves exercise duration and peak oxygen consumption in older patients with heart failure: a subgroup analysis of the PEECH trial. Congest Heart Fail. 2006; 12(6):307-11
11. Hunt SA, Abraham WT, Chin MH et al. ACC/AHA 2005 guideline update for the diagnosis and management of congestive heart failure in the adult:  A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to update the 2001 guidelines for evaluation and management of heart failure.) http://circ.ahajournals.org/cgi/reprint/112/12/e154  (Verified 07/13/09)
12. Jessup M, Abraham WT, Casey DE at al. 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.109.192064 (verified 07/13/2009)
13. Barsheshet A, Hod H, Shechter M at al. The effects of external counter pulsation therapy on circulating endothelial progenitor cells in patients with angina pectoris. Cardiology. 2008;110(3):160-6. Epub 2007 Dec 4.
14. Bondesson S, Pettersson T, Erdling A at al. Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris. Coron Artery Dis. 2008 Dec;19(8):627-34.
15. Shechter M, Matetzky S, Feinberg MS et al. External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris. J Am Coll Cardiol 2003; 42(12):2090-5
16. Holubkov R, Kennard E, Foris JM et al. Comparison of patients undergoing enhanced external counterpulsation and percutaneous coronary intervention for stable angina pectoris. Am J Cardiol 2002; 89(10):1182-6
17. Estahbanaty G, Samiei N, et al. Echocardiographic Characteristics Including Tissue Doppler Imaging After Enhanced External Counterpulsation Therapy. Am Heart Hosp J. 2007; 5: 241-6
18. Loh PH, Louis AA, Windram J et al. The immediate and long-term outcome of enhanced external counterpulsation in treatment of chronic stable refractory angina. J Intern Med 2006;259:276-84
19. Pettersson T, Bondesson S, Cojocaru D et al. One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation.  BMC Cardiovasc Disord 2006;6:28
20. Campbell AR, Satran D, Zenovich AG at al. Enhanced external counterpulsation improves systolic blood pressure in patients with refractory angina. Am Heart J. 2008 Dec;156(6):1217-22. Epub 2008 Oct 5.
21. Erdling A, Bondesson S, Pettersson T at al. Enhanced external counter pulsation in treatment of refractory angina pectoris: two year outcome and baseline factors associated with treatment failure. BMC Cardiovasc Disord. 2008 Dec 18;8:39.
22. Kumar A, Aronow WS, Vadnerkar A at al. Effect of enhanced external counterpulsation on clinical symptoms, quality of life, 6-minute walking distance, and echocardiographic measurements of left ventricular systolic and diastolic function after 35 days of treatment and at 1-year follow up in 47 patients with chronic refractory angina pectoris. Am J Ther. 2009 Mar-Apr;16(2):116-8.
23. Soran O, Kennard ED, Bart BA, et al. Impact of external counterpulsation treatment on emergency department visits and hospitalizations in refractory angina patients with left ventricular dysfunction. Congest Heart Fail. 2007; 13(1):36-40
24. Soran O, Kennard ED, Kelsey SF et al. Enhanced external counterpulsation as treatment for chronic angina in patients with left ventricular dysfunction: a report from the International EECP Patient Registry (IEPR). Congest Heart Fail  2002; 8(6):297-302, 312
25. Lawson WE, Hui JC, Barsness GW et al. for the IEPR Investigators. (2004). Effectiveness of enhanced external counterpulsation in patients with left main disease and angina. Clin Cardiol, 8:459-63.
26. Lawson WE, Silver MA, Hui JC et al. Angina patients with diastolic versus systolic heart failure demonstrate comparable immediate and one-year benefits from enhanced external counterpulsation. J Card Fail  2005;11(1):61-6
27. Lawson WE, Kennard ED, Holubkov R et al. Benefit and safety of enhanced external counterpulsation in treating coronary artery disease patients with a history of congestive heart failure. Cardiology 2001; 96(2):78-84
28. Soran O, Fleishman B, Demarco T et al. Enhanced external counterpulsation in patients with heart failure: a multicenter feasibility study. Congestive Heart Failure 2002;8(4):204-8, 227
29. Soran O, Kennard ED, Kfoury AG et al.  Two-year clinical outcomes after enhanced external counterpulsation (EECP) therapy in patients with refractory angina pectoris and left ventricular dysfunction (report from The International EECP Patient Registry).  Am J Cardiol  2006;97(1):17-20

Cross References

Regence ConsumerTx: Enhanced External Counterpulsation (EECP)

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