journal
vf Internal Medicine 1991 : 229: 357-362
AWNIS
0954682091OOO654
Acupuncture in angina pectoris : does acupuncture have a specific effect ?* S. B A L L E G A A R D , C. N. MEYER & W. TROJABORG From the Department o j Internal Medicine P and the Deportment of Neurophgsiology. Rigshospitalet. Universitg Hospital of Copenhagen. Copenhagen. Denmark
Abstract. Ballegaard S, Meyer CN, Trojaborg W (Medical Department P and Department of Neurophysiology, Rigshospitalet, University Hospital of Copcnhagen, Copenhagen, Denmark). Acupuncture in angina pectoris: does acupuncture have a specific effect? Journal of Internal Medicine 1991: 229: 357-362.
To overcome the methodological problems of blinding the patients and the acupuncturist in acupuncture trials, 33 patients with stable angina pectoris. who were randomized to either genuine or sham acupuncture, received electroacupuncture by another acupuncturist, and the change in skin temperature was recorded. It was found that the change in skin temperature correlated significantly with the degree of improvement following both genuine and sham acupuncture. Fourteen patients with no decrease in skin temperature exhibited a significantly better response to acupuncture than 19 patients who showed a decrease in skin temperature (G 11). In the former group, there was a 15% median improvement in exercise tolerance (G I1 OX), a 67% improvement in anginal attack rate (C I1 38%). and an 84% improvement in nitroglycerine consumption (C I1 50%).A significant correlation was found between the duration of disease and the effect of acupuncture. It is concluded that both genuine and sham acupuncture have a specific effect on some angina pectoris patients in addition to the effect of pharmacological therapy. K e g w o r d s : acupuncture, angina pectoris, skin temperature.
Introduction New medical or surgical treatment for angina pectoris. initially reported to be very successful in openor single-blinded studies, could not be reproduced subsequently when double-blinded studies were performed [l].Trials to evaluate the effect of acupuncture in angina pectoris face great methodological problems ; neither the acupuncturist nor the patient can be regarded as blinded due to the very nature of the treatment. The present study was conducted in order to evaluate (i) the effect of acupuncture on elimination of methodological problems in angina pectoris. (ii) to determine whether sham acupuncture can be regarded as an inactive control treatment, and (iii) to distinguish responders from non-responders to acupuncture. Presented at the Third International Symposium, ‘The Pain Clinic’. Italy. 1 5 September 1988. Abbreviations: TENS = transcutaneous electrical nerve stimulation, PRP = pressure-rate-product. r = correlation coefficient.
Material and methods Study population
Of 2 1 5 patients recruited consecutively, 166 individuals were excluded before the first trial and a further 16 subjects before the second trial, as they did not fulfil the entry criteria. The remaining 33 patients suffered from stable exercise-induced angina pectoris of > 6 months duration, had a positive exercise test ( 21 mm ST-depression in one or more leads), and were free of other diseases causing chest pain. Their clinical data are summarized in Table 1. Each patient underwent two trials performed by different acupuncturists. In the first trial, 49 patients received 10 treatments for their angina pectoris within a 3-week period. They were randomized to either genuine acupuncture [2] (24 patients), or to sham acupuncture (25 patients) with needles inserted in points within the same spinal segments as the acupoints, but outside the Chinese meridian
357 16-2
358
S. BALLEGAARD et al.
Table 1. General characteristics of study group Characteristic
n
Number of patients completing the study
33
Males/females
26/7
Median age (years) (range)
6 7 (49-78) 3 (1-12)
Median duration of angina pectoris ( y e a 4 (range) Previous myocardial infarct
12
Medical treatment in addition to nitroglycerine Beta-blockers Calcium antagonists Diuretics Nitroglycerine with prolonged effect Clinical status at entry to study (median and interquartile range) Exercise tolerance (Wm i d ) Maximal PRP/lOOO (mmHg min-') Delta PRP/ 1000 (mmHg min-') Number of anginal attacks/3 weeks Nitroglycerine consumption (0.25 mg tablets per 3 weeks) Daily well-being on an ordinal scale per 3 weeks
system. The effect was evaluated blindly from the following exercise test variables : exercise tolerance, maximal pressure-rate-product (PRP), delta PRP (difference in PRP between rest and maximal exercise), and variables from 3-week diaries: nitroglycerine consumption, anginal attack rate and daily well-being. Daily well-being was classified as follows : (1)= very good, (2) = good, (3) = fair, (4) = not good, 5 = poor. It was found that both treatments had a beneficial effect, there being no significant difference between the groups [3], and therefore all patients were treated as one group on entry to the second trial, the test acupuncture, during which skin temperature was recorded while the patient received genuine acupuncture. The test acupuncture was performed in the supine position. The left hallux and index finger were washed with ether before a standard thermocouple was applied to the skin (Type ELLAB AH 3, Copenhagen, Denmark). The temperature was measured by a mirror-galvanometer, graded in 0 . 1 "C (Type ELLAB TE 3, Copenhagen, Denmark). The patient rested for 30 min before the insertion of needles at point Hegu (Large Intestine 4) bilaterally, located between the first and second metacarpal bone [2]. The disposable stainless steel needles (Seirin Kasei Co. Ltd. Shimizu, Japan) were
10 11 8 5
390 (233-660) 22.2 (18.7-26.8) 9.6 (7.1-11) 23 ( 1 2 4 0 ) 18 (9-51) 4 6 (42-56)
stimulated electrically at 2 Hz at an intensity just below pain threshold using ' Electro-stimulator ' (E. Warner Joergensen Automatic Ltd, Birkeroed. Denmark). Skin temperature was recorded during the electroacupuncture stimulation at 3-min intervals for the first 21 min and then after 35 and 50 min. The median room temperature was 22.5 "C (range 20.0-24.0 "C). To ensure that the patients were unaware of the connection between the two trials, they were informed that the test acupuncture was to evaluate a possible relationship between skin temperature, sensory threshold, pain threshold, and pain tolerance threshold after electroacupuncture. The time period between the last acupuncture treatment and the test acupuncture ranged from 7 d to 7 months. All patients gave their informed consent before entering the study, which was approved by the local ethics committee. The relationship (r = correlation coefficient) between the data obtained from the two trials was estimated by Kendall non-parametric analysis. Intrapersonal differences were evaluated by a rank-sum test for the paired data (Wilcoxon). Differences between groups were evaluated by a rank-sum test for unpaired data (Mann-Whitney). A significance level of 5% was chosen.
ACUPUNCT JRE IN ANGINA PECTORIS
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T = 20 min
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359
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-
.-
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Fig. 1. Relationship between
changes in skin temperature on the index finger during the test acupuncture and changes in clinical variables for angina pectoris after the therapeutic acupuncture. A positive correlation coefficient indicates that an increase in clinical variables corresponds to stable or increased skin temperature. T = duration of test acupuncture (min). n = 33: * P < 0.05: **P < 0.01.
Nitroglycerine consumption
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Fig. 2. Relationship between
changes in skin temperature on the index finger after 50 min of test acupuncture and changes in clinical variables for angina pectoris after acupuncture treatment. n = 33. (a) Delta PRP. P < 0.05: (b) exercise tolerance. P < 0.05: (c) anginal attack rate. I' < 0.05: (d) nitroglycerine consumption, P < 0.01. The point (x/y) = (0.8/-84) is a doublepoint.
Results The clinical effect of acupuncture (genuine and sham taken together) correlated with the change in skin
11111111111 - 4 - 3 - 2 -I 0 I 2 3 4 5
Change in skin temperature
(OC)
temperature on the index finger during genuine acupuncture (Fig. 1). Twelve patients showed an increase in skin temperature, two showed no change (group l),whereas 19 patients showed a decrease
360
S. B A L L E G A A R D et al.
225 0
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Pretreatment
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Fig. 3. (a) Median nitroglycerine (NTG) consumption and (b) anginal attack rate before and after acupuncture for Group 1 ( 0 )and Croup 2 (m), expressed as absolute values. *P < 0.05. **P < 0.01.
A PRP
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n
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Anginal ottock rate
(group 2) (Fig. 2). No significant correlation was found with regard to the change in temperature on the hallux. The median temperature at the start of the test acupuncture was 33.6 "C (range 27.835.4 "C) on the index finger and 26.1 "C (range 20.3-35.2 "C) on the hallux. A n increase in exercise tolerance was present in 12 patients in group 1 (median 15%) and 7 patients in group 2 (median value, 0%)(P < 0.02). A similar improvement in delta PRP occurred in 10 patients in group 1 (median value, 1 6 %) compared to 8 patients in group 2. (median value, -3%) (P < 0.1). The nitroglycerine consumption and anginal attack rate decreased in all the patients in group 1 (median values, 8 4 and 67%, respectively) compared to 18 and 1 6 patients in group 2 (median values, 50 and 38% respectively) (Fig. 3). Nine patients in group 1 reported improved daily well-being (median value, + 9 ) compared to 6 patients in group 2 (median value, - 1) (P < 0.05). No significant change in maximum PRP was observed. A minimal antianginal benefit, in addition to that of pharmacological therapy, was defined as a 1 5 % increase in exercise tolerance and/or delta PRP, together with a 30% reduction in anginal attack rate and/or nitroglycerine consumption. The sensitivity and specificity of the test for identification of patients who showed this favourable response were 0.81 and 0.73, respectively. When the outcome of the test acupuncture for patients who received genuine or sham acupuncture was calculated individually, a significant correlation was found for both groups (Fig. 4). The correlation coefficient between the duration of angina pectoris and effect of acupuncture. estimated as the change in exercise tolerance, was - 0.3 7 (P < 0.02); delta PRP was -0.13 (P > O . l ) , the angina Nitroglycerine consumDtion
0.2
0.4 it
Fig. 4. Relationship betwcen changes in clinical variables for angina pectoris treated with genuine ( 0 )or sham (m) acupuncture and changcs in skin temperature on the index tinger during the test acupuncture. rr = 14 for genuine and ri = 19 for sham acupuncture. *I' < 0.05.
ACUPUNCTURE I N ANGINA PECTORIS
attack rate was 0.27 (P c O . l ) , and nitroglycerine consumption was 0.42 (P c 0.05). The 1 9 patients who had experienced angina pectoris for < 4 years exhibited a significant increase in exercise tolerance (median value, 1 2 %, interquartile range, 0-25 %), compared to 1 4 patients with a longer duration of the disease (P c 0.05).
Discussion In the first trial it was found that both genuine and sham acupuncture had a beneficial clinical effect, and no significant difference could be detected between the effect of the two treatments. On this basis it was concluded that the observed effect was due to either placebo or a specific noxious stimulation of the dermatome of the heart [3]. This problem can be solved by correlating the results of the two trials. It was found that the change in skin temperature on the index finger, but not on the hallux, was correlated with the clinical effect. The clinical effect is influenced by placebo [ l . 41. It has not been established whether placebo affects the normal skin temperature, but if the results were due to a placebo effect, then a uniform effect of the whole organism would be expected [4-61, and thus a significant correlation for both the index finger and the hallux. With regard to the analgesic effect of acupuncture, it has been found that the local effect exceeds the general effect [7] and in experimental studies on musculocutaneus skin flaps on rats, locally applied acupuncture increased skin blood flow as well as survival time [8, 91. The acupuncture point used in the test acupuncture was located next to the index finger, and the correlation with the clinical effect was'significant for both genuine and sham acupuncture. These findings suggest that the effect of acupuncture was at least partly due to specific noxious stimulation of a dermatome. In the present study, the change in skin temperature on the index finger during a test acupuncture identified a group of patients who derived more benefit from acupuncture than another group. A similar test has previously been used to select patients for acupuncture analgesia during brain surgery [lo], and to select patients for TENS treatment for nonmalignant limb pain [l11. An increase in skin temperature following acupuncture has been shown to be due to sympathetic inhibition [ l o , 121. We found that the responding patients reported pain relief, and that they showed increased exercise tol-
361
erance and delta PRP, without a corresponding increase in maximum PRP, indicating that PRP at the same level of exercise was reduced after acupuncture. Similar results have been found for TENS treatment of patients with angina pectoris [13], the effect being due to peripheral vasodilation induced by a decrease in sympathetic tone [14]. Thus patients with angina pectoris who benefit from acupuncture might be able to achieve a higher degree of peripheral vasodilation due to sympathetic inhibition than those who do not benefit. Why acupuncture and TENS produce sympathetic inhibition in some patients and not others is a topic to be addressed by future studies. It should be emphasized that the classification of one patient without a change in skin temperature during the test acupuncture as a responder, and another, who showed a decrease of 0.1 "C, as a nonresponder, was performed arbitrarily to test the Chinese hypothesis [lo]. The fact that it was possible to distinguish responders from non-responders on the basis of a temperature difference of 0.1 "C stresses the need for further studies on the point of discrimination, reproducibility, and optimal testing methodology before the test is used clinically. Furthermore, to evaluate the predictive value of the test acupuncture, a new trial, in which it is performed before the therapeutic acupuncture, is required. The results of the present study indicate that both genuine and sham acupuncture have a specific effect on some angina pectoris patients who might be identified by a test acupuncture. The effect of acupuncture is more pronounced when the disease is of short duration.
Acknowledgements We wish to thank F. Petersen, MD, and A. Pietersen, MD, of the Cardiological Laboratory, Rigshospitalet, University Hospital, Copenhagen, for evaluation of the patients and operation of the working ECG, and J. Nyboe, for assistance with the statistical analysis. We are also grateful to P. Nathan, National Hospital for Nervous Disease, London, for critical review of the manuscript. We thank the following for financial support: The Augustinus Foundation, BP Oil Company Ltd, The Manufacturer Mads Clausen's Foundation, Denmark's Health Foundation, The Foundation of 1870, The Gangsted Foundation, The Gerda and Aage Haenschs Foundation, Director Ib Henriksen's Foundation, The Hindsgaul Foundation, The Illum Foundation, Jul P. Justesen Foundation, The
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LK-Nes Foundation, Lily Lunds Foundation, Arvid Nilsson's Foundation, and the Foundation of the Saxild Family.
8
9
References
10
1 Benson H. McCallie J r DF. Angina pectoris and the placebo
effect. N Engl 1 Med 1979: 300 (25): 1424-9. 2 The Beijing College of Traditional Chinese Medicine. Essentials ojChinese Acupuncture. Beijing : Foreign Language Press, 1980 : 3 19-52. 3 Ballegaard S. Pedersen F. Pietersen A, Nissen VH. Olsen NV. Effect of acupuncture in moderate. stable angina pectoris: a controlled study. 1 Intern Med 1990: 227: 25-30. 4 Kaada B. The mystery of the placebo. A Pavlovian reflex for activation of self-healing mechanisms. Tidsskr Nor LaegeJoren 1986: 106: 635-41. 686. 5 Rosenthal R. Interpersonal expectations: effects of the experimenter's hypothesis. In: Rosenthal R. Rosnow PL. eds. ArtiJact in fleliavioral Research. New York: Academic Press. 1969: 182-279. 6 Wichramasekera I. A conditioned response model of the placebo effect. Predictions from the model. In: White L. Tursky B. Schwartz GE. eds. Placebo-Theory. Research. and Mechanisms. New York: Guildford Press, 1985: 255-7. 7 Andersson SA. Ericson T. Holmgren E. Lindquist G. Electro-
11
12
13
14
acupuncture, effect on pain threshold measure with electrical stimulation of teeth. Brain Res 1973: 63: 393-6. Jansen G. Lundeberg T. Kjartansson J. Samuelson UE. Acupuncture and sensory neuropeptides increase cutaneous blood flow in rats. Neurosci Lett 1989: 9 7 : 305-9. Jansen G. Lundeberg T. Samuelson UE. Thomas M. Increased survival of ischaemic musculocutaneous flaps in rats after acupuncture. Acta Phgsiol Scand 1989 : 135 : 555-8. Cao Xiao-ding C. Shao-feng X. Wen-xiao L. Inhibition of sympathetic nervous system by acupuncture. Aciipiinct Electrother Res 1983: 8 : 25-35. Abram SE. Asiddao CB. Reynolds AC. lncreastd skin temperature during transcutaneous electrical stimulation. Ariestli Analg 1980: 59: 22-5. Kaada B. Eiesen 0. In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation. 11. Serotonin implicated. Gen Pharmacol 1983: 14: 635-41. Mannheimer C. Carisson CA. Emanuelson H. Vedin A, Waagstein F. Wilhelmsson C. The effects of transcutaneous electrical nerve stimulation in patients with severe angina pectoris. Circulation 1985 : 71 : 308-1 6. Emanuelsson H. Mannheimer C. Waagstcin F. Wilhemsson C. Catecholamine during pacing-induced angina pectoris and the effect of transcutaneous electrical nerve stimulation. A m Heart 1 1 9 8 7 : 114 (6): 1360-66.
Received 21 May 1990. accepted 17 November 1990. Correspondence: Soeren Ballegaard. MD. Acupuncture Center, Soelystvej 4. DK-2930 Klampenborg. Denmark.
vf Internal Medicine 1991 : 229: 357-362
AWNIS
0954682091OOO654
Acupuncture in angina pectoris : does acupuncture have a specific effect ?* S. B A L L E G A A R D , C. N. MEYER & W. TROJABORG From the Department o j Internal Medicine P and the Deportment of Neurophgsiology. Rigshospitalet. Universitg Hospital of Copenhagen. Copenhagen. Denmark
Abstract. Ballegaard S, Meyer CN, Trojaborg W (Medical Department P and Department of Neurophysiology, Rigshospitalet, University Hospital of Copcnhagen, Copenhagen, Denmark). Acupuncture in angina pectoris: does acupuncture have a specific effect? Journal of Internal Medicine 1991: 229: 357-362.
To overcome the methodological problems of blinding the patients and the acupuncturist in acupuncture trials, 33 patients with stable angina pectoris. who were randomized to either genuine or sham acupuncture, received electroacupuncture by another acupuncturist, and the change in skin temperature was recorded. It was found that the change in skin temperature correlated significantly with the degree of improvement following both genuine and sham acupuncture. Fourteen patients with no decrease in skin temperature exhibited a significantly better response to acupuncture than 19 patients who showed a decrease in skin temperature (G 11). In the former group, there was a 15% median improvement in exercise tolerance (G I1 OX), a 67% improvement in anginal attack rate (C I1 38%). and an 84% improvement in nitroglycerine consumption (C I1 50%).A significant correlation was found between the duration of disease and the effect of acupuncture. It is concluded that both genuine and sham acupuncture have a specific effect on some angina pectoris patients in addition to the effect of pharmacological therapy. K e g w o r d s : acupuncture, angina pectoris, skin temperature.
Introduction New medical or surgical treatment for angina pectoris. initially reported to be very successful in openor single-blinded studies, could not be reproduced subsequently when double-blinded studies were performed [l].Trials to evaluate the effect of acupuncture in angina pectoris face great methodological problems ; neither the acupuncturist nor the patient can be regarded as blinded due to the very nature of the treatment. The present study was conducted in order to evaluate (i) the effect of acupuncture on elimination of methodological problems in angina pectoris. (ii) to determine whether sham acupuncture can be regarded as an inactive control treatment, and (iii) to distinguish responders from non-responders to acupuncture. Presented at the Third International Symposium, ‘The Pain Clinic’. Italy. 1 5 September 1988. Abbreviations: TENS = transcutaneous electrical nerve stimulation, PRP = pressure-rate-product. r = correlation coefficient.
Material and methods Study population
Of 2 1 5 patients recruited consecutively, 166 individuals were excluded before the first trial and a further 16 subjects before the second trial, as they did not fulfil the entry criteria. The remaining 33 patients suffered from stable exercise-induced angina pectoris of > 6 months duration, had a positive exercise test ( 21 mm ST-depression in one or more leads), and were free of other diseases causing chest pain. Their clinical data are summarized in Table 1. Each patient underwent two trials performed by different acupuncturists. In the first trial, 49 patients received 10 treatments for their angina pectoris within a 3-week period. They were randomized to either genuine acupuncture [2] (24 patients), or to sham acupuncture (25 patients) with needles inserted in points within the same spinal segments as the acupoints, but outside the Chinese meridian
357 16-2
358
S. BALLEGAARD et al.
Table 1. General characteristics of study group Characteristic
n
Number of patients completing the study
33
Males/females
26/7
Median age (years) (range)
6 7 (49-78) 3 (1-12)
Median duration of angina pectoris ( y e a 4 (range) Previous myocardial infarct
12
Medical treatment in addition to nitroglycerine Beta-blockers Calcium antagonists Diuretics Nitroglycerine with prolonged effect Clinical status at entry to study (median and interquartile range) Exercise tolerance (Wm i d ) Maximal PRP/lOOO (mmHg min-') Delta PRP/ 1000 (mmHg min-') Number of anginal attacks/3 weeks Nitroglycerine consumption (0.25 mg tablets per 3 weeks) Daily well-being on an ordinal scale per 3 weeks
system. The effect was evaluated blindly from the following exercise test variables : exercise tolerance, maximal pressure-rate-product (PRP), delta PRP (difference in PRP between rest and maximal exercise), and variables from 3-week diaries: nitroglycerine consumption, anginal attack rate and daily well-being. Daily well-being was classified as follows : (1)= very good, (2) = good, (3) = fair, (4) = not good, 5 = poor. It was found that both treatments had a beneficial effect, there being no significant difference between the groups [3], and therefore all patients were treated as one group on entry to the second trial, the test acupuncture, during which skin temperature was recorded while the patient received genuine acupuncture. The test acupuncture was performed in the supine position. The left hallux and index finger were washed with ether before a standard thermocouple was applied to the skin (Type ELLAB AH 3, Copenhagen, Denmark). The temperature was measured by a mirror-galvanometer, graded in 0 . 1 "C (Type ELLAB TE 3, Copenhagen, Denmark). The patient rested for 30 min before the insertion of needles at point Hegu (Large Intestine 4) bilaterally, located between the first and second metacarpal bone [2]. The disposable stainless steel needles (Seirin Kasei Co. Ltd. Shimizu, Japan) were
10 11 8 5
390 (233-660) 22.2 (18.7-26.8) 9.6 (7.1-11) 23 ( 1 2 4 0 ) 18 (9-51) 4 6 (42-56)
stimulated electrically at 2 Hz at an intensity just below pain threshold using ' Electro-stimulator ' (E. Warner Joergensen Automatic Ltd, Birkeroed. Denmark). Skin temperature was recorded during the electroacupuncture stimulation at 3-min intervals for the first 21 min and then after 35 and 50 min. The median room temperature was 22.5 "C (range 20.0-24.0 "C). To ensure that the patients were unaware of the connection between the two trials, they were informed that the test acupuncture was to evaluate a possible relationship between skin temperature, sensory threshold, pain threshold, and pain tolerance threshold after electroacupuncture. The time period between the last acupuncture treatment and the test acupuncture ranged from 7 d to 7 months. All patients gave their informed consent before entering the study, which was approved by the local ethics committee. The relationship (r = correlation coefficient) between the data obtained from the two trials was estimated by Kendall non-parametric analysis. Intrapersonal differences were evaluated by a rank-sum test for the paired data (Wilcoxon). Differences between groups were evaluated by a rank-sum test for unpaired data (Mann-Whitney). A significance level of 5% was chosen.
ACUPUNCT JRE IN ANGINA PECTORIS
T=10 rnin
T = 20 min
T:35rnin
359
T =50 min
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-
.-
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0.2
0
-
-
?
B
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6
o.I
Anginal attack rote
Fig. 1. Relationship between
changes in skin temperature on the index finger during the test acupuncture and changes in clinical variables for angina pectoris after the therapeutic acupuncture. A positive correlation coefficient indicates that an increase in clinical variables corresponds to stable or increased skin temperature. T = duration of test acupuncture (min). n = 33: * P < 0.05: **P < 0.01.
Nitroglycerine consumption
*
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m
g
)
.
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Fig. 2. Relationship between
changes in skin temperature on the index finger after 50 min of test acupuncture and changes in clinical variables for angina pectoris after acupuncture treatment. n = 33. (a) Delta PRP. P < 0.05: (b) exercise tolerance. P < 0.05: (c) anginal attack rate. I' < 0.05: (d) nitroglycerine consumption, P < 0.01. The point (x/y) = (0.8/-84) is a doublepoint.
Results The clinical effect of acupuncture (genuine and sham taken together) correlated with the change in skin
11111111111 - 4 - 3 - 2 -I 0 I 2 3 4 5
Change in skin temperature
(OC)
temperature on the index finger during genuine acupuncture (Fig. 1). Twelve patients showed an increase in skin temperature, two showed no change (group l),whereas 19 patients showed a decrease
360
S. B A L L E G A A R D et al.
225 0
t
( 0
I
NS
Pretreatment
"
c
e
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Poattreatment
NS
30
I U f
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20
D
a 10
Pretreotment
Posttreotment
Treatment phose ( 3 w w h d
Fig. 3. (a) Median nitroglycerine (NTG) consumption and (b) anginal attack rate before and after acupuncture for Group 1 ( 0 )and Croup 2 (m), expressed as absolute values. *P < 0.05. **P < 0.01.
A PRP
+ 01 c
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Exercise tolerance
n
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O
it
Anginal ottock rate
(group 2) (Fig. 2). No significant correlation was found with regard to the change in temperature on the hallux. The median temperature at the start of the test acupuncture was 33.6 "C (range 27.835.4 "C) on the index finger and 26.1 "C (range 20.3-35.2 "C) on the hallux. A n increase in exercise tolerance was present in 12 patients in group 1 (median 15%) and 7 patients in group 2 (median value, 0%)(P < 0.02). A similar improvement in delta PRP occurred in 10 patients in group 1 (median value, 1 6 %) compared to 8 patients in group 2. (median value, -3%) (P < 0.1). The nitroglycerine consumption and anginal attack rate decreased in all the patients in group 1 (median values, 8 4 and 67%, respectively) compared to 18 and 1 6 patients in group 2 (median values, 50 and 38% respectively) (Fig. 3). Nine patients in group 1 reported improved daily well-being (median value, + 9 ) compared to 6 patients in group 2 (median value, - 1) (P < 0.05). No significant change in maximum PRP was observed. A minimal antianginal benefit, in addition to that of pharmacological therapy, was defined as a 1 5 % increase in exercise tolerance and/or delta PRP, together with a 30% reduction in anginal attack rate and/or nitroglycerine consumption. The sensitivity and specificity of the test for identification of patients who showed this favourable response were 0.81 and 0.73, respectively. When the outcome of the test acupuncture for patients who received genuine or sham acupuncture was calculated individually, a significant correlation was found for both groups (Fig. 4). The correlation coefficient between the duration of angina pectoris and effect of acupuncture. estimated as the change in exercise tolerance, was - 0.3 7 (P < 0.02); delta PRP was -0.13 (P > O . l ) , the angina Nitroglycerine consumDtion
0.2
0.4 it
Fig. 4. Relationship betwcen changes in clinical variables for angina pectoris treated with genuine ( 0 )or sham (m) acupuncture and changcs in skin temperature on the index tinger during the test acupuncture. rr = 14 for genuine and ri = 19 for sham acupuncture. *I' < 0.05.
ACUPUNCTURE I N ANGINA PECTORIS
attack rate was 0.27 (P c O . l ) , and nitroglycerine consumption was 0.42 (P c 0.05). The 1 9 patients who had experienced angina pectoris for < 4 years exhibited a significant increase in exercise tolerance (median value, 1 2 %, interquartile range, 0-25 %), compared to 1 4 patients with a longer duration of the disease (P c 0.05).
Discussion In the first trial it was found that both genuine and sham acupuncture had a beneficial clinical effect, and no significant difference could be detected between the effect of the two treatments. On this basis it was concluded that the observed effect was due to either placebo or a specific noxious stimulation of the dermatome of the heart [3]. This problem can be solved by correlating the results of the two trials. It was found that the change in skin temperature on the index finger, but not on the hallux, was correlated with the clinical effect. The clinical effect is influenced by placebo [ l . 41. It has not been established whether placebo affects the normal skin temperature, but if the results were due to a placebo effect, then a uniform effect of the whole organism would be expected [4-61, and thus a significant correlation for both the index finger and the hallux. With regard to the analgesic effect of acupuncture, it has been found that the local effect exceeds the general effect [7] and in experimental studies on musculocutaneus skin flaps on rats, locally applied acupuncture increased skin blood flow as well as survival time [8, 91. The acupuncture point used in the test acupuncture was located next to the index finger, and the correlation with the clinical effect was'significant for both genuine and sham acupuncture. These findings suggest that the effect of acupuncture was at least partly due to specific noxious stimulation of a dermatome. In the present study, the change in skin temperature on the index finger during a test acupuncture identified a group of patients who derived more benefit from acupuncture than another group. A similar test has previously been used to select patients for acupuncture analgesia during brain surgery [lo], and to select patients for TENS treatment for nonmalignant limb pain [l11. An increase in skin temperature following acupuncture has been shown to be due to sympathetic inhibition [ l o , 121. We found that the responding patients reported pain relief, and that they showed increased exercise tol-
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erance and delta PRP, without a corresponding increase in maximum PRP, indicating that PRP at the same level of exercise was reduced after acupuncture. Similar results have been found for TENS treatment of patients with angina pectoris [13], the effect being due to peripheral vasodilation induced by a decrease in sympathetic tone [14]. Thus patients with angina pectoris who benefit from acupuncture might be able to achieve a higher degree of peripheral vasodilation due to sympathetic inhibition than those who do not benefit. Why acupuncture and TENS produce sympathetic inhibition in some patients and not others is a topic to be addressed by future studies. It should be emphasized that the classification of one patient without a change in skin temperature during the test acupuncture as a responder, and another, who showed a decrease of 0.1 "C, as a nonresponder, was performed arbitrarily to test the Chinese hypothesis [lo]. The fact that it was possible to distinguish responders from non-responders on the basis of a temperature difference of 0.1 "C stresses the need for further studies on the point of discrimination, reproducibility, and optimal testing methodology before the test is used clinically. Furthermore, to evaluate the predictive value of the test acupuncture, a new trial, in which it is performed before the therapeutic acupuncture, is required. The results of the present study indicate that both genuine and sham acupuncture have a specific effect on some angina pectoris patients who might be identified by a test acupuncture. The effect of acupuncture is more pronounced when the disease is of short duration.
Acknowledgements We wish to thank F. Petersen, MD, and A. Pietersen, MD, of the Cardiological Laboratory, Rigshospitalet, University Hospital, Copenhagen, for evaluation of the patients and operation of the working ECG, and J. Nyboe, for assistance with the statistical analysis. We are also grateful to P. Nathan, National Hospital for Nervous Disease, London, for critical review of the manuscript. We thank the following for financial support: The Augustinus Foundation, BP Oil Company Ltd, The Manufacturer Mads Clausen's Foundation, Denmark's Health Foundation, The Foundation of 1870, The Gangsted Foundation, The Gerda and Aage Haenschs Foundation, Director Ib Henriksen's Foundation, The Hindsgaul Foundation, The Illum Foundation, Jul P. Justesen Foundation, The
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LK-Nes Foundation, Lily Lunds Foundation, Arvid Nilsson's Foundation, and the Foundation of the Saxild Family.
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Received 21 May 1990. accepted 17 November 1990. Correspondence: Soeren Ballegaard. MD. Acupuncture Center, Soelystvej 4. DK-2930 Klampenborg. Denmark.
