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National Clinical Guidelines Centre (UK). Stable Angina: Methods, Evidence & Guidance [Internet]. London: Royal College of Physicians (UK); 2011 Jul. (NICE Clinical Guidelines, No. 126.)

18Pain Interventions and Refractory angina

18.1. Introduction

Stable angina presents as chest pain. Interventions are primarily related to addressing cardiac work by for example improving blood flow by medical treatment or revascularisation and by addressing the progression of underlying coronary artery disease. Chronic refractory angina has been defined as angina that cannot be controlled with optimal medical therapy and where revascularisation is unfeasible21. The decision as to when revascularisation is unfeasible is a decision made by interventional radiologists and cardiac surgeons. Revascularisation will also carry risks and an informed patient may decide that these risks outweigh possible benefits. The current UK national chronic refractory angina group‘s definition of chronic refractory angina is, “Chronic stable angina that persists despite optimal medication and when revascularisation is unfeasible or where the risks are unjustified. Interventions directed towards pain rather than towards coronary artery disease have been used for people with ‘refractory‘ angina.

The GDG choose not to make a decision on a definition of refractory angina. They considered that different definitions and inclusion criteria might have been used in different studies and considered it more appropriate to examine evidence for use of pain interventions in as wide a population of people with angina as possible. The evidence review therefore describes the populations included in each study. The GDG were addressed by Professor Michael Chester and Dr. Austin Leach from the National Angina Refractory Centre who also advised on the interventions to include in the evidence review.

The following pain interventions have been included in the review:

  • TENS (Transcutaneous electric nerve stimulation),
  • EECP (Enhanced external counter pulsation)
  • Acupuncture
  • Self-pain management programmes

The evidence review includes 1 paper on TENS (Transcutaneous Electric Nerve Stimulation), 3 papers on EECP (Enhanced external counter pulsation) and 3 papers on Acupuncture, 2 papers on self-management of pain. No studies were identified evaluating the effectiveness of opioids in the management of people with angina.

Table 18.1Pain interventions – Summary of evidence

StudyInterventionComparisonDuration of interventionStudy designNo of participantsFollow-upOutcomes
Manheimer 1985218TENSControl group did not receive TENS10 weeks. Three TENS treatment sessions of at least 1 hr each per day (morning, noon and evening)RCTN=23 (n=12 TENS and n=11). Severe angina pectoris (duration 1 to 20 years, functional class III or IV, NYHA). The antianginal pharmacological treatment taken at the beginning of the study was regarded as optimal. All patients had been considered for aortocoronary bypass surgery: one patient had undergone such a operation, five were waiting for surgery, and the remaining were being considered for surgical treatment.After 2 weeksMaximal total work during exercise was determined as a product of workload in watts and time in mins (W.min); ST segment depression during and after exercise; pain and dyspnea reported by the patient during and after exercise..; frequency of anginal attacks and consumption of short- acting nitroglycerin per week.
Arora 1999219EECPInactive counterpulsation (CP)35 hours of (once or twice/day) of active counterpulsation over a 4 to 7-week period.RCTN = 139 (n=EECP 72, n=67 inactive counterpulsation. Chronic stable angina- CCS I, II or III.

More than 70% of patients in each group had CCS class II or III and over 70% of each group had undergone prior CABG or angioplasty.
3 days after follow-up for angina pain counts, one week after treatment for exercise duration.Exercise test, Anginal pain counts, Nitroglycerin use.
Arora 2002219EECPInactive counterpulsation (CP).35 hours of (once or twice/day) of active counterpulsation over a 4 to 7-week period.RCTN = 139 (n=EECP 72, n=inactive counterpulsation 67); n=71 (36 in EECP and n=35 inactive CP). Chronic stable angina - CCS I, II or IIIAt end of treatment and 1 year after treatmentHealth related quality of life (HRQOL)
Loh 2008220EECPNo comparisonA standard course of 35 one hour treatment sessions. The patients received a mean of 33.3±9.6 hours of treatment over a mean period of 48 days.Before- After studyN=1427, CCS I, I, III angina. Anginal status: [CCS class I: 2.2% CCS class II: 8.6% CCS class III: 62.8% CCS class IV: 26.4%].

88% had prior PCI or CABG and 88% were unsuitable for further coronary intervention.
3 years (median 37 months)Anginal status (CCS class), weekly angina episode, nitroglycerin use, QOL (using a simple 5 point scale where 1 represents the worst and 5 represents the best QOL), clinical events (PCI, CABG, MI, death, MACE (composite of death/MI/CABG/PCI) and hospitalisation.
Ballegaard 1990221AcupunctureSham acupuncture.Ten (10) treatments in the supine position within 3 weeksRCTN=49 (n=24 in genuine acupuncture and n=25 sham acupuncture).

Clinically stable exercise induced angina pectoris for more than 6 months (2 or more anginal attacks per week). All patients on medical treatment.
Just after the treatment periodExercise test; no. of anginal attacks; activity at the time of the pain; nitroglycerin consumption (diaries); daily well being on an ordinal scale; global evaluation of the effect of the treatment on an ordinal scale:
Ballegaard 1986222AcupunctureSham acupuncture.Seven (7) treatments in the supine position for 3 weeksRCTN=26 (n=13 in active acupuncture and n=13 in sham acupuncture).

Stable, medically resistant, exercise provoked angina pectoris (functional class II–1V NYHA). The patients were selected among 56 consecutive patients with a positive evaluation with regard to aortocoronary bypass surgery
Immediately after the 9 week treatment period.Exercise tests variables (Exercise tolerance, difference in pressure rate product between rest and maximum exercise, maximal PRP during exercise, maximum ST depression and length of time maximum ST depression); anginal attacks, activity at the time of the pain attack and nitroglycerin consumption (from diaries); subjective global evaluation by the patient at the end of the trial : improvement of general well-being after treatment/no improvement of general well-being after treatment.
Richter 1991223AcupunctureTablet placebo.The treatment was given 3 times per week during the 4 week period.RCT (cross over trial)N=21 (cross over). Patients with stable effort angina and at least five anginal attacks per week during the last 6 months, inspite of intensive antianginal treatment.

Bypass surgery had been performed in 8 patients, in two of them repeatedly, while 5 patients were still waiting for operation.
Immediately after the 4 treatment periodExercise test, self rating quality of life questionnaire, no. of anginal attacks.
McGillion 2008224Chronic Angina Self- Management Program (CASMP)Waiting list control (offered entry into the next available CASMP once post-test measures were completed).The psycho education programme given in two-hour sessions weekly, over a six- week period by a registered nurse using a group format.RCTn=130 were randomised, n=66 to the CASMP and n=64 to the waiting list control group.

Chronic stable angina patients.
3 months from start of treatmentHealth Related Quality of Life (HRQOL) which included the SF- 36 and the SAQ (Seattle Angina Questionnaire)
Payne 1994225Pain management programmestandard medical careThe pain management programme administered over three consecutive weekly sessions (length of sessions not reported).RCTN =52 (N=26 pain management treatment and N=26 controls).

Episodes of chest pain or discomfort in the previous 4 weeks in patients with diagnosed coronary artery disease.
6 months.Pain frequency and intensity; frequency of NTG usage; mood and psychological distress.

18.2. Transcutaneous electric nerve stimulation (TENS)

18.2.1. Clinical question

What is the clinical/cost effectiveness of TENS in people with stable angina?

18.2.2. Clinical evidence

The “Review Protocol” for this topic can be found in Appendix C, the “Search Strategies” in Appendix D, the “List of Included and Excluded Studies” in Appendix E1, the “Clinical Evidence Tables” in Appendix E2, and the “Forest Plots” in Appendix F.

There was one RCT218 evaluating the effectiveness of TENS in patients with severe angina pectoris.

The “Review Protocol” for this topic can be found in Appendix C, the “Search Strategies” in Appendix D, the “List of Included and Excluded Studies” in Appendix E1, the “Clinical Evidence Tables” in Appendix E2, and the “Forest Plots” in Appendix F.

Table 18.2TENS vs. control (no TENS) for stable angina – Quality assessment & Summary of findings

Quality assessmentSummary of findings
No of patientsEffectQuality
No of studiesDesignLimitationsInconsistencyIndirectnessImprecisionOther considerationsTENS vs. control (no TENS) (Follow-up 2 weeks after treatment)controlRelative (95% CI)Absolute
Exercise tolerance (W.min) (follow-up 2 weeks; better indicated by higher values)
Mannheimer 1985218randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none1110-MD 9 lower (170.42 lower to 152.42 higher)⊕⊕○○

LOW
ST segment depression (mm) during exercise (follow-up 2 weeks; better indicated by lower values)
Mannheimer 1985218randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none1110-MD 0.2 lower (1.36 lower to 0.96 higher)⊕⊕○○

LOW
ST segment depression (mm) after exercise (follow-up 2 weeks; better indicated by lower values)
Mannheimer 1985218randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none1110-MD 0.2 higher (0.97 lower to 1.37 higher)⊕⊕○○

LOW
Frequency of angina attacks per week (follow-up 2 weeks; better indicated by lower values)
Mannheimer 1985218randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none1110-MD 4 lower (21.98 lower to 13.98 higher)⊕⊕○○

LOW
Nitroglycerin consumption per week (follow-up 2 weeks; better indicated by lower values)
Mannheimer 1985218randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none1110-MD 17 higher (9.31 lower to 43.31 higher)⊕⊕○○

LOW
a

Mannheimer 1985[212]: Randomised. Blind outcome assessment (ST segment changes were measured blindly by two independent observers). Method of randomisation not reported. Allocation concealment not reported. Small sample size. Loss to follow-up not reported. ITT not reported. No blinding of participants (not possible due to the kind of intervention)

b

Upper and lower confidence limit crosses the minimal important difference.

18.2.3. Economic evidence

No relevant economic evaluations comparing TENS with any other intervention were identified.

18.2.4. Evidence statement

ClinicalTENS vs. control

Mannheimer 1985[212]: Evidence from one RCT shows that there was no significant difference between TENS treatment and control group for exercise tolerance (W.min) (MD −9.00 [−170.42, 152.42]); ST segment depression (mm) during exercise (MD −0.20 [−1.36, 0.96]); ST segment depression after exercise (MD 0.20 [−0.97, 1.37]); frequency of angina attack per week (MD −4.00 [−21.98, 13.98]); and nitroglycerin consumption per week (MD 17.00 [−9.31, 43.31]) [follow-up 2 weeks after treatment]
EconomicNo economic evidence was found.

18.2.5. Recommendations and link to evidence

RecommendationDo not offer the following interventions to manage stable angina:
  • transcutaneous electrical nerve stimulation (TENS)
  • enhanced external counterpulsation (EECP)
  • acupuncture.
Relative values of different outcomesThe outcomes considered as important during the development of the review protocol for pain interventions included: improvement in anginal symptoms (angina frequency and nitroglycerin consumption), exercise tolerance, mortality, major cardiac events, hospitalisation, revascularisation, QoL and adverse events.
Trade off between clinical benefits and harmsThe evidence identified on TENS reported on three outcomes including frequency of anginal attacks, exercise tolerance and nitroglycerin consumption. TENS is not clinically effective with respect to any of these three outcomes.

There is no evidence of clinical benefit arising from the use of TENS in stable angina patients.
Economic considerationsNo published health-economic evaluation of TENS was identified. The intervention is associated with costs to the NHS but there is no evidence of clinical benefit. TENS was therefore considered not cost-effective.
Quality of evidenceThe available evidence was of low quality as assessed by GRADE with a very small sample size (n=23) and short follow- up period (2 weeks).
Other considerationsThe GDG considered that current evidence base is weak and shows no effectiveness of TENS. TENS should not be used unless new evidence emerges that demonstrates that TENS is clinically and cost-effective in people with stable angina.

18.3. Enhanced external counterpulsation (EECP)

18.3.1. Clinical question

What is the clinical/cost effectiveness of EECP in people with stable angina?

18.3.2. Clinical evidence

The “Review Protocol” for this topic can be found in Appendix C, the “Search Strategies” in Appendix D, the “List of Included and Excluded Studies” in Appendix E1, the “Clinical Evidence Tables” in Appendix E2, and the “Forest Plots” in Appendix F.

There were 3 papers (1 RCT, one sub-study of the RCT and one Before-After study) evaluating the effectiveness of EECP in patients with chronic stable angina and refractory angina.

Table 18.3EECP vs. inactive CP for stable angina

Quality assessmentSummary of findings
No of patientsEffectQuality
No of studiesDesignLimitations InconsistencyIndirectnessImprecisionOther considerationsEECPinactive CP (Follow-up 3 days after treatment for angina pain counts, one week after treatment for exercise duration)Relative (95% CI)Absolute
Exercise duration (sec) (change scores) (follow-up after 1 week) (follow-up 1 weeks; better indicated by higher values)
Arora 1999219randomised trialsserious (a) no serious inconsistencyno serious indirectnessserious imprecision (d)none5758-MD 16 higher (15.86 lower to 47.86 higher)⊕⊕○○

LOW
Time to >1mm ST segment depression (Sec) (change scores) (follow-up after 1 week) (follow-up 1 weeks; better indicated by higher values)
Arora 1999219randomised trialsserious (a) no serious inconsistencyno serious indirectnessno serious imprecisionnone5656-MD 41 higher (9.13 to 72.87 higher)⊕⊕⊕○

MODERATE
Angina episodes/day (change scores) (follow-up after 3 days) (follow-up 3 days; better indicated by lower values)
Arora 1999219randomised trialsserious (a) no serious inconsistencyno serious indirectnessserious imprecision (d)none7166-MD 0.24 lower (0.83 lower to 0.35 higher)⊕⊕○○

LOW
NTG use/day (change scores) (follow-up after 3 days) (follow-up 3 days; better indicated by lower values)
Arora 1999219randomised trialsserious (a) no serious inconsistencyno serious indirectnessno serious imprecisionnone7166-MD 0.22 lower (0.55 lower to 0.11 higher)⊕⊕⊕○

MODERATE
Adverse events (no. of patients) (up to the end of treatment) (c)
Arora 1999219randomised trialsserious (a) no serious inconsistencyno serious indirectnessserious (b)none39/71 (54.9%)17/66 (25.8%)RR 2.13 (1.35 to 3.38)291 more per 1000 (from 90 more to 613 more)⊕⊕○○

LOW
a

Arora 1999[213]: Multicentre randomised study. Baseline characteristics reported. The EECP group and inactive CP group were not balanced at baseline, the patients in the EECP group had significantly longer duration of angina and higher proportion of patients with previous MI. Allocation concealment reported. 2/139 withdrew prior to first treatment. 1/66 in inactive CP and 12/71 in EECP lost to follow-up [more drop out from the EECP than the control group]. No data reported on long term outcomes especially cardiac mortality. Completed trial: N = 124: EECP, n= 59; Inactive CP, n=65. ITT analysis used (but not for all outcomes). ITT was not reported for ST segment depression and exercise duration. This may overestimate the treatment effect. Data not well reported. Very short follow-up

b

Less than 300 events

c

The adverse experiences (device related) were: Paresthesia, edema, swelling, skin abrasion, bruise, blister, pain (legs, back). The adverse experiences (non device related) were: viral syndrome, anxiety, dizziness, tinnitus, GI disturbance, headache, blood pressure change, epitaxis, angina, other chest pain, A/V arrhythmia, heart rate change, respiratory.

d

95% CI includes no effect and the upper and lower CI crosses the MID.

ARORA 2002226 (MUST EECP trial; EECP vs. control)

This is a sub-study of the (MUST EECP trial assessing HRQOL [Health related quality of life] at one year follow-up).

Population:

MUST EECP trial N=138 (n=EECP 71, n=inactive counterpulsation n= 66) 119 male. Age (mean): 62±9 (no EECP); 64±9 (EECP); p<0.1.

Data for sudstudy with HRQoL was available only for n=71 (35 in no EECP and n=36 EECP, 65 male. Age (mean ±SD): 62.7 ± 9.7 (no EECP), 65.3± 8.1 [Hence there is a high risk that this sample is not representative of the study population]

Outcome: Health related quality of life (HRQOL). Four primary outcomes were used in the analysis: the physical functioning, bodily pain and social functioning subscales of the SF-36, and QOL score. The 36 item Short-Form Health Survey (SF-36) and the cardiac version of the Quality of Life Index (QIL) used for measuring HQOL. The SF-36 comprises 36 items that yield 8 multi item scales that measure physical functioning, work role disability due to emotional problems, bodily pain, general health perceptions, vitality, social functioning, work role disability due to emotional problems, mental health, and a single item evaluation of change in health. The QIL is in 2 parts: Part 1 measures satisfaction with various aspects of life as they are impacted by the respondent’s cardiac health. Part 2: Measures the importance of these same aspects of life to the respondent personally.

Results:

  1. Baseline to end of treatment: Both EECP and inactive CP groups reported significant improvements in physical functioning, bodily pain, and cardiac specific health and functioning from baseline to end of treatment. The size of the improvement in HQOL parameters was always larger for the EECP than for inactive CP; however, this difference was only statistically significant for one of the four primary parameters: social functioning. Those in the EECP group reported a substantially greater increase in their abilities to participate in social activities with family and friends than did those in the inactive CP, who, on average, reported a decrease in social activity. [Values not reported]
  2. Baseline to 1 year follow-up: At 1 year follow-up, the EECP group maintained statistically significant improvements in HQOL across all primary HQOL parameters, where as the inactive CP group only maintained a significant improvement in the physical functioning scale. At 1 year follow-up, improvements for the EECP group were significantly greater than those for the inactive CP group on 3 of 4 primary parameters: bodily pain, social functioning, and cardiac specific health and functioning [no values reported]

Loh 2008220 (International EECP Patient Registry [IPER])

This is a Before-After study. This study is the 3 year follow-up of the patients in the International EECP Patient Registry (IEPR)

Population: N=1427. Five thousand patients from 99 American and 9 international centres were enrolled between Jan 1998 and July 2001. Consecutive patients from each centre who had at least 1 hour of EECP treatment were enrolled. The mean age was 66.3±10.8 years and 72% were men.76% had multivessel coronary disease.88% had prior PCI or CABG and 88% were unsuitable for further coronary intervention. The Anginal status of patients was: CCS class I: 2.2%; CCS class II: 8.6%; CCS class III: 62.8%; CCS class IV: 26.4%.

Intervention: EECP. A standard course of 35 one hour treatment sessions was recommended. The patients received a mean of 33.3±9.6 hours of treatment over a mean period of 48 days.

Follow-up: 3 years (median 37 months)

Outcome: The primary outcome measure was Anginal status (CCS class). The other outcomes were weekly angina episode, nitroglycerin use, QOL (using a simple 5 point scale where 1 represents the worst and 5 represents the best QOL), clinical events (PCI, CABG, MI, death, MACE (composite of death/MI/CABG/PCI) and hospitalisation.

Results: Immediately post EECP, the proportion of patients who suffered from CCS Class III/IV angina reduced from 89.2% to 24.9%, p<0.001. The CCS class improved by at least 1 class in 77.9% of the patients and by 2 classes in 38%. 16.3% of patients had no angina. These were sustained in 74% patients whose anginal status was documented at 3 year follow-up. At 3 years, 36.4% of the patients had class II or milder angina. The Cumulative 3 year repeat EECP and major cardiovascular event rates: (Percentage (95% CI)) was: Repeat EECP: 22.5% (20.1% –24.9%); PCI: 16.4% (14.3% –18.5%); CABG: 7.5% (6%–9%); MI: 11.8% (10%–13.7%); Death- 17% (14.9%–19.1%); MACE: 40.8% (38.8%–43.5%). Of the patients who responded to the QOL questionnaires there was sustained improvement in their QOL after 3 years, p<0.001(results reported graphically).

18.3.3. Economic evidence

One study227 was included that compared EECP with no treatment. This is summarised in the economic evidence profile below. See also Economic Evidence Tables in Appendix G.

Table 8.4EECP vs. no treatment- Economic study characteristics

StudyLimitationsApplicabilityOther Comments
McKenna 2009227Potentially serious limitations (a)Direct applicabilityDecision model based on the MUST-EECP trial, included in the review of clinical effectiveness.
a

The analysis was based on limited data (one small RCT). Utilities were obtained from an algorithm converting SF-36 to EQ-5D. Durability of benefits obtained from expert opinion. The model does not consider: the effect of the intervention on mortality or myocardial infarction, the cost of escalating medical treatment over time, costs associated with no intervention.

Table 8.5EECP vs. no treatment - Economic summary of findings

StudyIncremental cost (£)Incremental effects (QALYs)ICERUncertainty
McKenna 20092274,750 (a)0.255 (b)£18,643/QALYOne-way sensitivity analysis: results were sensitive to the probability of sustaining QoL benefits over time and to the cost of EECP.

Results were not sensitive to the rate of repeat EECP within two years or to the discount rates used.

Worst/best case scenario: if QoL benefits from EECP are only sustained in the first year, the ICER was £63,000.

If QoL benefits are sustained over a lifetime, the ICER becomes £5,830.

Monte-Carlo simulation: EECP was cost-effective in 44.4% of the simulations.
a

2008 GBP. Costs included were capital cost of EECP machine, equipment replacement costs, consumables, staffing costs, overheads, repeat operations. Cost of no treatment was assumed to be null. Cost data were obtained from personal communication and price list of supplier.

b

Quality of life improvements were calculated as EQ-5D scores using an algorithm to convert the SF-36 scores from the study into EQ-5D. Utilities after one year were estimated with expert elicitation techniques (frequency chart).

18.3.4. Evidence statements

ClinicalEECP vs. inactive CP

Arora 1999219 (MUST EECP trial): Evidence from one RCT shows that time to >1 mm ST segment depression (sec) increased significantly in the EECP compared to inactive CP (MD 41.00 [9.13 to 72.87]). Adverse events were significantly higher in the EECP group compared to inactive CP (RR 2.13 (1.35 to 3.38). There was no significant difference between EECP and inactive CP for exercise duration (sec) (MD 16.00 [−15.86 to 47.86]); angina episodes/day (MD −0.24 [−0.83 to 0.35]); NTG use/day (MD −0.22 [−0.55 to 0.11]) [follow-up 3 days after treatment for angina pain counts, one week after treatment for exercise duration].

EECP vs. control

Arora 2002226 (MUST EECP trial): Evidence from one RCT shows that both EECP and inactive CP groups reported statistically significant improvements in physical functioning, bodily pain, and cardiac specific health and functioning from baseline to end of treatment. At 1 year follow-up, the EECP group maintained statistically significant improvements in HQOL across all primary HQOL parameters, where as the inactive CP group only maintained a statistically significant improvement in the physical functioning scale. At 12 month follow-up, improvements in HQOL for the EECP were significantly greater than those for the inactive CP group on three of four primary parameters (SF-36 scale): bodily pain, social functioning and cardiac specific health and functioning but not physical functioning. [Follow-up 12 months]

EECP Patient Registry (no comparison group)

Loh 2008220 (International EECP Patient Registry [IPER]): Evidence from one Before-After study shows that immediately post EECP, the proportion of patients who suffered from CCS Class III/IV angina reduced from 89.2% to 24.9%, p<0.001. The CCS class improved by at least 1 class in 77.9% of the patients and by 2 classes in 38%. 16.3% of patients had no angina. These were sustained in 74% patients whose anginal status was documented at 3 year follow-up. Immediately post EECP, 76% of the patients experienced at least 50% reduction in frequency of angina. This was sustained at 3 year follow-up. Of the patients who responded to the QOL questionnaires there was sustained improvement in their QOL after 3 years, p<0.001(no values reported) [follow-up 3 years]
EconomicThe cost-effectiveness of EECP is very uncertain depending on the sustained effectiveness of the intervention. This evidence is directly applicable but it has potentially serious limitations.

18.3.5. Recommendations and link to evidence

RecommendationDo not offer the following interventions to manage stable angina:
  • transcutaneous electrical nerve stimulation (TENS)
  • enhanced external counterpulsation (EECP)
  • acupuncture.
Relative values of different outcomesThe outcomes considered important during the development of the review protocol for pain interventions included: improvement in anginal symptoms (angina frequency and nitroglycerin consumption), exercise tolerance, mortality, major cardiac events, hospitalisation, revascularisation, QoL and adverse events.
Trade off between clinical benefits and harmsEvidence from the MUST EECP trial showed a statistically significant improvement in one exercise test variable (time to ST depression) in the EECP group relative to the control group (one week follow-up period). The GDG did not consider this improvement to be clinically significant. Furthermore there were more adverse events in the EECP group when compared to the control group over the 7 week treatment period.

The registry study (International EECP Patient Registry (IPER)) showed significant improvement in CCS angina class after 3 years. During this follow-up period there was repeat EECP in 22.5% of patients, PCI in 16.4% patients, CABG in 7.5% of patients and death in 17% of patients.

Adverse events were significantly higher in the EECP group when compared to the control group over the 7 week treatment period.
Economic considerationsThere is high uncertainty over the cost-effectiveness of EECP in people with stable angina mainly due to the unknown long- term benefits of the intervention.
Quality of evidenceThe available evidence on EECP is weak. It is based on one RCT (MUST EECP) and one registry study (International EECP Patient Registry (IPER)).

The MUST EECP trial was a small study with a high risk of bias. The randomisation scheme was not explained and the short follow-up period (1 year) limits conclusions regarding the durability of treatment effects.

The IPER registry study has serious limitations. Only patients from centres with at least 80% compliance in follow-up data were included (5000 patients were enrolled but only 1427 patients were analysed).

No evidence was available on the long-term safety of EECP.

The economic evidence was directly applicable but it had potentially serious limitations.
Other considerationsThe GDG considered that people with angina that has not responded to drug or revascularisation options or for whom these options are inappropriate or undesirable present a significant clinical problem. They considered it important, however, that interventions offered to these patients should have robust evidence base. Without such an evidence base the GDG considered it misleading to offer such interventions to patients and it was more appropriate for healthcare professionals to acknowledge the limitations of interventions available and provide information, education and support for patients.

18.4. Acupuncture

18.4.1. Clinical question

What is the clinical/cost effectiveness of Acupuncture in people with stable angina?

18.4.2. Clinical evidence

The “Review Protocol” for this topic can be found in Appendix C, the “Search Strategies” in Appendix D, the “List of Included and Excluded Studies” in Appendix E1, the “Clinical Evidence Tables” in Appendix E2, and the “Forest Plots” in Appendix F.

There were 3 RCTs221–223 evaluating the effectiveness of acupuncture in people with stable angina.

Data for the 3 RCTS could not be analysed as the standard deviations were not reported. Hence results have been reported narratively.

Ballegaard 1990221

Population: N=49 (n=24 in genuine acupuncture and n=25 sham acupuncture). The Median age (years) of the patients was 67 yrs in genuine and 66 yrs in sham acupuncture.

Intervention: Genuine acupuncture. The genuine acupuncture was given according to traditional Chinese medicine, each patient receiving 10 treatments in the supine position within 3 weeks.

Comparison: Sham acupuncture.

Outcome: Exercise test; no. of anginal attacks; activity at the time of the pain; nitroglycerin consumption (diaries); daily well being on an ordinal scale, using the terms very good (given value 1), good (2), fair (3), not good (4), bad (5); global evaluation of the effect of the treatment on an ordinal scale: much improved, somewhat improved, slightly improved, unchanged, slightly worse, somewhat worse, much worse.

Follow-up: Immediately after treatment

Results:

  1. Exercise test variables
    There was no significant between group differences for any of the exercise variables. Exercise variables (genuine (n=24) vs. sham acupuncture (n=25): Exercise tolerance (%): median change +9, range −25 to +184 vs. median change +4 (−16 to +135); Maximal PRP (%):−1 (−12 to +47) vs. +5 (−22 to +25); Delta PRP (%): + 3 (−38 to +145) vs. +4 (−28 to + 78); Time to ST segment depression (%): median change 0 (−42 to +100) vs. median change 0 (−40 to +40); Time to end of ST depression (%):median change +9 (−75 to +600) vs. median change 0 (−58 to +300); Maximum ST depression (mm): median change 0 (−1.0 to +0.5) vs. 0 median change (−1.0 to +1.5); Time with minimum 1 mm ST depression (%):median change +15 (−79 to +490) vs. median change +5 (−72 to +200); Time to onset of pain (%):median change +10 (−32 to +107) vs. median change +10 (−39 to +55); Post exercise pain duration (%): median change 0 (−47 to +700) vs. median change 0 (−77 to +78).
  2. Subjective variables
    Within both groups there was a significant decrease in both anginal attack rate and nitroglycerin consumption. After treatment all patients receiving genuine acupuncture decreased nitroglycerin consumption (median change −54%, range −14 to −100%). Anginal attack rate was reduced in 13 of 14 patients (93%) (median change −41%, range +18 to −95%). Nitroglycerin consumption and anginal attack rate were reduced in 15 of 16 patients (94%) receiving sham acupuncture. The median change being −53% (range +20 to −100%) and −55% (range +23% to −100%) respectively. Daily well being was improved in 14 out of 23 (61%) in both groups (median improvement +1 arbitrary value in both groups). Concerning global evaluation, 75% of the patients treated by genuine acupuncture reported improvement in their general condition after the end of the treatment and 6m months later 67% still felt the improvement. Among those treated by sham acupuncture 84% reported improvement and 6 months later 72% still felt it.

Ballegaard 1986222

Population: N=26 (n=13 in active acupuncture and n=13 in sham acupuncture).

Intervention: Active acupuncture. During the 3 weeks treatment period all patients received seven treatments in the supine position.

Control: Sham acupuncture.

Follow-up: Immediately after the 9 week treatment period.

Results: Patients receiving genuine acupuncture had a significantly higher dPRP (Pressure rate product) than patients receiving sham acupuncture, respectively. [Maximal PRP (mmHgmin-1): 24.640 vs. 13.530; Delta PRP (mmHgmin-1): 12.580 vs. 6.592]. There was no significant difference between genuine and sham acupuncture, respectively for: Exercise tolerance (Wmin): 550 (150 to 1300) vs. 256 (100 to 1700); Time to maximal ST depression (min): 2 (0 to 7.5) vs. 2 (0 to 4.5); and Size of maximal ST depression (mm): 1 (0 to 3) vs. 1 (0 to 2); No. of anginal attacks per 3 weeks: 55 (8 to 168) vs. 66 (41 to 149); and nitroglycerin consumption (0.25 mg tablets per 3 weeks): 39 (1 to 193) vs. 30 (0 to 152). Six of the 12 patients in the active treatment group and one of 12 patients in the sham treatment group reported improvement in general well being after treatment (p=0.10). No complications or adverse effects were observed. The study period consisted of: 3 weeks of pre treatment control; after randomisation 3 weeks of treatment, during which the patients received either active or sham acupuncture, and 3 weeks of post treatment control.

Richter 1991223

Population: N=21 (cross over study).

Intervention: Acupuncture. The treatment was given 3 times per week during the 4 week period.

Comparison: Tablet placebo.

Follow-up: Immediately after the 4 week treatment period (2 weeks wash out period between the treatment periods)

Results: During acupuncture treatment, 14 patients showed a reduced number of anginal attacks compared with placebo. The no. of attacks was unchanged in the remaining 7 patients; no worsening was observed in any of the patients. In the whole group, the average number of anginal attacks/week was 12.1 during the run-in period, 6.1 during the acupuncture period and 10.6 during the placebo period. The differences between acupuncture and both run-in and placebo periods were statistically significant (p<0.01). The results of the exercise tests did not show any significant difference in maximal physical performance at the end of the acupuncture period compared with placebo, the mean values being 104.2 W and 101.4 W respectively. However, maximal workload until onset of chest pain was significantly increased after acupuncture compared with placebo (94.3 W vs. 81.9 W, P<0.05). Mean chest pain score at maximal workload improved significantly after acupuncture compared with placebo (mean (0.81 W and 1.38, p<0.01). ST segment depression at maximal workload was significantly reduced after acupuncture compared with placebo (mean 0.71 mm vs. 1.03 mm, p<0.01). Similar results were obtained for ST segment depression at maximal comparable workload (mean 0.63 mm vs. 0.87 mm, p<0.01). [Standard deviations not reported]. Concerning the self-rating life quality questionnaire, the score was significantly improved for chest pain, physical performance, peripheral coldness, pessimism, vertigo and relaxation (p<0.05). The statistical significance could not be proved for anxiety, tiredness, sleep disturbances and gastro-intestinal symptoms. No adverse effect of acupuncture was observed. [mean values and standard deviations not reported]

18.4.3. Economic evidence

One study228 focusing on the addition of acupuncture and self-education to medical treatment was found but it was excluded as it had serious limitations due to the study design (within-group comparison) and it was partially applicable (cost estimates from the USA).

18.4.4. Evidence statements

ClinicalAcupuncture vs. sham acupuncture

Ballegaard 1990221: Evidence from one RCT shows that there was no significant difference between genuine acupuncture and sham acupuncture for exercise variables; anginal attack rate; and nitroglycerin consumption [follow-up 3 days after treatment for angina pain counts, one week after treatment for exercise duration].

Ballegaard 1986222: Evidence from one RCT shows that compared to patients receiving sham acupuncture the patients receiving active acupuncture increased cardiac work capacity significantly,. There was no significant difference between the groups for exercise tolerance, time to maximal ST depression (min); size of maximal ST depression (mm): and nitroglycerin consumption [Follow-up immediately after 9 week treatment period]

Acupuncture vs. placebo

Richter 1991223: Evidence from one randomised cross over trial shows that compared to placebo treatment acupuncture significantly reduced anginal attacks per week); maximal workload until onset of chest pain was significantly increased after acupuncture compared with placebo chest pain at maximal workload improved significantly after acupuncture compared with placebo ST segment depression at maximal workload was significantly reduced after acupuncture compared with placebo and ST segment depression at maximal comparable workload was significantly reduced after acupuncture compared with placebo. There was no significant difference in maximal physical performance at the end of the acupuncture period compared with placebo [follow-up immediately after 4 week treatment period]
EconomicNo economic evidence was included on this intervention.

18.4.5. Recommendations and link to evidence

RecommendationDo not offer the following interventions to manage stable angina:
  • transcutaneous electrical nerve stimulation (TENS)
  • enhanced external counterpulsation (EECP)
  • acupuncture.
Relative values of different outcomesThe outcomes considered as important during the development of the review protocol for pain interventions included: improvement in anginal symptoms (angina frequency and nitroglycerin consumption), exercise tolerance, mortality, major cardiac events, hospitalisation, revascularisation, QoL and adverse events.
Trade off between clinical benefits and harmsOne RCT223 showed some improvement in angina and exercise test variables when compared to tablet placebo. However there was no improvement in angina or exercise test variables in two RCTs221,222 that compared acupuncture to sham acupuncture.

There is no other evidence of clinical benefit arising from the use of acupuncture in stable angina patients.
Economic considerationsNo published health-economic evaluation of acupuncture was included. The intervention is not cost-effective as it generates costs without being effective at improving the outcomes considered.
Quality of evidenceEvidence was obtained from 3 low quality RCTs221–223. Each of these RCTs had small sample size (<50 patients); outcomes were measured immediately after treatment with no longer term follow-up. The methodology of the trials was not well reported and the derived data was not analysable. Hence the GDG was not confident in the results of these trials.
Other considerationsThe GDG considered that people with angina which has not responded to drug or revascularisation options or for whom these options are inappropriate or undesirable present a significant clinical problem. They considered it important however, that interventions offered to these patients should have robust evidence base. The GDG did not consider that the evidence for acupuncture supported its use in people with angina. The GDG recognised that some people with angina may also experience chest pain that is not cardiac in origin and that acupuncture may have some role in these circumstances.

18.5. Self management of pain

18.5.1. Clinical question

What is the clinical/cost effectiveness of self management of pain in people with stable angina?

18.5.2. Clinical evidence

The “Review Protocol” for this topic can be found in Appendix C, the “Search Strategies” in Appendix D, the “List of Included and Excluded Studies” in Appendix E1, the “Clinical Evidence Tables” in Appendix E2, and the “Forest Plots” in Appendix F.

There were 2 RCTs224,225 comparing Psycho educational programmes with control/standard medical care for self management of pain in stable angina.

McGillion 2008224 (CASMP vs. control)

Population: n=130 were randomised, n=66 to the CASMP and n=64 to the waiting list control group.

Intervention: The Chronic Angina Self-Management Program (CASMP) is a standardized psycho education programme given in two-hour sessions weekly, over a six-week period.

The CASMP is an adaptation of Lorig et al.’s Chronic Disease Self-Management Program (CDSMP, 1999 Stanford University). The programme was delivered by a registered nurse using a group format (e.g., 8–15 patients) in a comfortable classroom setting. Key pain related content includes relaxation and stress management techniques, energy conservation, symptom monitoring and management techniques, medication review, seeking emergency assistance, diet, and managing emotional responses to cardiac pain. Programme sessions were offered both day and evening and participants were encouraged to bring a family member or friend if they wished. A facilitator manual specified the intervention protocol in detail to ensure consistent delivery of the CASMP across sessions.

Comparison: Waiting list control: The patients in this group were offered entry into the next available CASMP once post-test measures were completed.

Outcomes: The primary outcome was Health Related Quality of Life (HRQOL) which included the SF-36 and the SAQ (Seattle Angina Questionnaire). The secondary outcome was enabling skill, reflected by CSA patients’ self-efficacy and resourcefulness to self-manage their pain.

Follow-up: 3 months

Table 18.6Chronic angina self management Program (CASMP) vs. control (Follow-up 3 months from start of treatment) for stable angina

Quality assessmentSummary of findings
No of patientsEffectQuality
No of studiesDesignLimitationsInconsistencyIndirectnessImprecisionOther considerationsChronic angina self management Program (CASMP)control (Follow-up 3 months from start of treatment)Relative (95% CI)Absolute
Physical functioning (SF-36) (range 0–100 -higher score better functioning) (change scores) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none5760-MD 5.98 higher (2.59 to 9.37 higher)⊕⊕○○

LOW
Role physical functioning (SF-36) (change scores) (range 0–100) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 1.6 higher (2.5 lower to 5.7 higher)⊕⊕⊕○

MODERATE
Bodily pain (SF-36) (change scores) (range 0–100) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 2.3 higher (0.94 lower to 5.54 higher)⊕⊕⊕○

MODERATE
General Health (SF-36) (change scores) (0–100) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none5760-MD 3.87 higher (1.3 to 6.44 higher)⊕⊕○○

LOW
Angina frequency (SAQ) (range 0–100- higher scores better functioning) (change scores) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 9.2 higher (1.48 to 16.92 higher)⊕⊕⊕○

MODERATE
Angina stability (SAQ) (range 0–100) (change scores) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 15.1 higher (4.11 to 26.09 higher)⊕⊕⊕○

MODERATE
Disease perception (SAQ) (range 0–100) (change scores) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious(a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 6.6 higher (1.18 lower to 14.38 higher)⊕⊕⊕○

MODERATE
Physical limitation (SAQ) (range 0–100) (change scores) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious(a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 5.5 higher (0.24 lower to 11.24 higher)⊕⊕⊕○

MODERATE
Treatment satisfaction (SAQ) (range 0–100) (change scores) (follow-up 3 months; range of scores: 0–100; better indicated by higher values)
McGillion 2008224randomised trialsserious(a)no serious inconsistencyno serious indirectnessno serious imprecisionnone5760-MD 4.9 higher (3.05 lower to 12.85 higher)⊕⊕⊕○

MODERATE
Self-Efficacy to manage disease (Self-efficacy Scale )range scores 10–100 -higher scores better) (change scores) (follow-up 3 months; range of scores: 10–100; better indicated by higher values)
McGillion 2008224randomised trialsserious (a)no serious inconsistencyno serious indirectnessserious (b)none5760-MD 8.6 higher (2.76 to 14.44 higher)⊕⊕○○

LOW
a

McGillion 2008[218]: Randomised. Allocation concealment reported. 9/66 (14%) in the intervention group and 4/64 (6%) in the control group. There are more patients in the intervention group who were lost to follow-up but there are no systematic differences between the two groups with respect to loss of participants. The study follow-up period was limited to three months after baseline for both groups. ITT used. No blinding of participants and outcome assessors.

b

Lower CI crosses MID.

Additional data

Payne 1994225 (Self Pain management programme vs. control)

Data was not analysed for the following study as it was poorly reported:

Population: n=52. Participants were 52 male veterans (26 in the treatment and 26 controls). To qualify for the study, patients were required to meet the following criteria: (a) diagnosis of CAD, or positive diagnostic evaluation, such as an exercise stress test, thallium 201 scan or coronary angiogram (b) self report of at least 4 episodes of chest pain or discomfort in the previous 4 weeks (c) 18–65 yrs of age (d) no hospitalisation within past 30 days (e) no current physical disorder associated with severely disabling symptoms or a recent change in symptoms (f) no history of heart valve replacement (g) no history of cardiac transplant surgery.

Intervention: A pain management programme administered over three consecutive weekly sessions (length of sessions not reported). The goals were to 1) educate patients regarding the role of psychological factors in pain and pain control and 2) teach participants an integrated set of self management skills to modify cognitions, behaviours and affective responses considered likely to adversely impact on the experience of chest pain. Specific skills taught included pacing of physical activities (e.g. taking scheduled breaks), modification of dysfunctional, stress engendering thoughts using cognitive reframing and problem solving techniques, and relaxation training via diaphragmatic breathing.

Control: Received standard medical care

Follow-up: 6 months.

Primary outcomes: No primary or secondary outcomes specified. Outcomes included: pain frequency and intensity; frequency of NTG usage; mood and psychological distress.

Results: There were no significant differences between groups with regard to pain frequency, pain intensity, psychological and other factors at 6 months. Actual data for results not reported.

18.5.3. Economic evidence

No economic studies were found on this question.

18.5.4. Evidence statements

ClinicalSelf management programme vs. control

McGillion 2008224: Evidence from one RCT shows that Physical functioning (SF-36) (MD 5.98 [2.59 to 9.37]), General Health (SF-36) (MD 3.87 [1.30 to 6.44]), Angina frequency (SAQ) (MD 9.20 [1.48 to 16.92], Angina stability (SAQ) (MD 15.10 [4.11 to 26.09]); and self-efficacy to manage disease (self-efficacy scale) (MD 8.60 [2.76 to 14.44]) were significantly improved in the CASMP compared to control. There was no significant difference between CASMP and control for Role physical functioning (SF-36) (MD 1.60 [−2.50 to 5.70]); bodily pain (SF-36) (MD 2.30 [−0.94 to 5.54]);disease perception (SAQ) (MD 6.60 [−1.18 to 14.38]) ; physical limitation (SAQ) (MD 5.50 [−0.24 to 11.24]) and treatment satisfaction (SAQ) (MD 4.90 [−3.05 to 12.85]) [Follow-up 3 months from start of treatment]

Payne 1994225: Evidence from one RCT shows that there were no significant differences between Pain management programme compared to control (standard care) with regard to pain frequency, pain intensity, psychological and other factors. (actual values for results not reported). [Follow-up 6 months]
EconomicNo economic evidence was available on this question.

18.5.5. Recommendations and link to evidence

RecommendationOffer people whose stable angina has not responded to drug treatment and/or revascularisation comprehensive re-evaluation and advice, which may include:
  • exploring the person’s understanding of their condition
  • exploring the impact of symptoms on the person’s quality of life
  • reviewing the diagnosis and considering non- ischaemic causes of pain
  • reviewing drug treatment and considering future drug treatment and revascularisation options
  • acknowledging the limitations of future treatment
  • explaining how the person can manage the pain themselves
  • specific attention to the role of psychological factors in pain
  • development of skills to modify cognitions and behaviours associated with pain.
Relative values of different outcomesQuality of Life outcomes were considered to be most important in assessing the effectiveness of self- management including various outcomes measured by the SF-36 health survey (physical functioning, bodily pain and general health), as well as those of the Seattle Angina Questionnaire (angina frequency and stability, disease perception, physical limitation and treatment satisfaction) and self-efficacy to manage disease.
Trade off between clinical benefits and harmsOne RCT224 showed statistically significant improvements in some Quality of Life variables including physical functioning, general health, angina frequency and stability, and self-efficacy to manage disease.



The studies reviewed do not provide a report on harms arising from self-management. The GDG considered it unlikely that significant harms would occur from involvement in a self-management programme.
Economic considerationsThe small increase in staff time cost is likely to be offset by the improvement in quality of life shown by the clinical review.
Quality of evidenceClinical evidence on self-management of pain that met our inclusion criteria for reviewing was obtained from one moderate quality RCT (n=117) and one low quality RCT (n=52) study as assessed by GRADE.



McGillion 2008224 conducted a small RCT of a psycho education programme [Chronic Angina Self-Management Program (CASMP)] in which those treated were compared to patients in a waiting list control group. The study found statistically reliable short-term improvements in some components of HRQL for those who participated in the CASMP as compared to the control group. The follow-up period was limited to three months after baseline and the long-term durability of the observed intervention effects is not known. Due to the nature of the treatment, the patients undergoing EECP could not be blinded, increasing the likelihood of a placebo effect. Further, all psycho education sessions were delivered by a single facilitator increasing the risk to external validity.



Payne 1994225 conducted a very small RCT evaluating a pain management programme and standard medical care compared with standard medical care alone. It found that there were short-term reductions in the number of self-reported chest pain episodes in treated subjects but this benefit was not evident at 6 month follow-up. The study however had a high risk of bias which would make the results unreliable.



No economic evidence was included on this intervention.
Other considerationsThe GDG made a recommendation on intervention for patients whose angina has not responded to treatment or for whom revascularisation is undesirable or inappropriate using the information presented by Professor Michael Chester and the evidence from the reviews on self management strategies.



The evidence for self-management strategies comes from two studies224,225. These programmes included a range of self management skills to modify cognitions, behaviours and affective responses considered likely to adversely impact on the experience of chest pain. Specific skills taught included components such as pacing of physical activities (e.g. taking scheduled breaks), modification of dysfunctional, stress engendering thoughts using cognitive reframing and problem solving techniques, and relaxation training via diaphragmatic breathing, energy conservation, symptom monitoring and management techniques, medication review, seeking emergency assistance, diet, and managing emotional responses to cardiac pain.
Copyright © 2011, National Clinical Guidelines Centre.

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