The effectiveness and safety of cupping therapy for stroke survivors: A systematic review and meta-analysis of randomized controlled trials ⑥ Discussion

• Mikyung Kim(1Department of Internal Medicine, College of Korean Medicine, Sangji University), Chang-ho Han(Department of Internal Medicine, College of Korean Medicine, Dongguk University)
• J Korean Med. 2021;42(4):75-101

To confirm the therapeutic effect of cupping therapy, one of the oldest interventions used across the world in multiple cultures5), scientific explorations have been attempted in modern times. Clinical trials have shown the potential of cupping therapy to be effective in a variety of diseases, including herpes zoster, facial palsy, acne, and cervical spondylosis, as well as pain^{33, 34)}.
Nevertheless, the mechanism of action of cupping remains unclear^35,36). However, the hypotheses that this intervention has local effects, including improving capillary and lymphatic circulation and extension of the underlying tissue, as well as systemic effects through activation of the neuroendocrine immune system resulting from the signaling molecules released from the blood vessels or tissues damaged by the cupping procedure^35,36), support the reason why cupping therapy can be applied to a variety of conditions across multiple systems of the whole body. Among the wide range of indications for cupping therapy, this study mainly presented the effects related to improving various complications in stroke survivors. This topic had already been
addressed by a previous systematic review published in 2010⁶⁾. However, at the time, sufficient data for meta-analysis were not obtained, so only narrative reviews of five clinical studies were possible⁶⁾. Since that previous review⁶⁾, more RCTs exploring the effect of cupping therapy in patients with stroke have been published. Therefore, we updated the findings of the previous study⁶⁾ by performing quantitative synthesis and qualitative evaluation of the currently available evidence. To the best of our knowledge, this study is the first to systematically review and meta-analyze RCTs on the effectiveness and safety of cupping therapy in stroke survivors.
The findings of this study showed the potential of cupping therapy as an add-on intervention for stroke survivors receiving conventional treatment. Among the various clinical outcomes, the additional benefits of wet cupping therapy for improving motor function of the upper limb were identified. Cupping therapy may have directly influenced upper limb motor function. However, considering that the original studies supporting this result were derived from patients with upper limb spasticity or hemiplegic shoulder pain and that the main findings of this systematic review also showed the advantage of cupping therapy for improving upper limb spasticity and reducing shoulder pain, we speculate that the effect of wet cupping for improving upper limb motor function may have been the result of muscle tone control and pain relief effects. However, this study could
not find evidence supporting the effect of cupping therapy on lower limb motor function.
Another finding of this study, supported by a moderate level of evidence, was that additional wet cupping therapy increased the positive response rate for poststroke spasticity. This effect of wet cupping therapy, although at a very low evidence level, was also confirmed by improvements in MAS scores and decreases in muscle tone of the affected biceps brachii, a flexor muscle that is generally overhypertensive in poststroke elbow spasticity. These findings seem to reflect the possibility that muscle relaxation, one of the known actions of cupping therapy³⁷⁾, could also work on upper limb spasticity in stroke patients.
Other studies have shown the positive potential of adjuvant cupping therapy in a wider range of indications. This study identified additional benefits of cupping therapy for improving ADLs, sensory dysfunction, shoulder pain, and shoulder-hand syndrome in stroke survivors, although the level of supportive evidence was low or very low. The effect of additional cupping to reduce pain and improve functions was confirmed in previous studies targeting patients with pain in various underlying diseases^4,5), and this study confirmed that this therapeutic action of cupping therapy could also work in stroke survivors.
This study also identified head-to-head studies comparing the effects of wet cupping therapy with active control interventions. The meta-analysis of these studies showed the possibility of wet cupping therapy being more beneficial than oral administration of baclofen in improving muscle tone and motor function in patients with poststroke upper arm spasticity. However, since there were only two small-sized studies supporting the findings and the level of evidence was low, it is necessary to be careful in interpreting this result. The findings of this study mainly supported the additional benefits of cupping therapy, especially wet cupping therapy, in upper limb motor function, upper limb spasticity, shoulder pain and shoulder-hand syndrome in stroke survivors.
Although the level of evidence was often low or very low, with rare studies with moderate levels of evidence, these findings may be helpful in determining priorities when considering application of cupping therapy for stroke survivors. Subgroup analysis of wet cupping or dry cupping studies showed that the number of wet cupping studies was higher, and the treatment
effect and evidence level were also higher than those of dry cupping studies. The fact that there were more studies on wet cupping than on dry cupping is consistent with the results of previous studies6,³³⁾. We found that not only was the number of studies on dry cupping therapy small, but the heterogeneity between those studies was also great. Therefore, it is difficult to draw conclusions about the effectiveness of dry cupping therapy on stroke based on the findings of this study. More clinical evidence needs to be collected.
Further consideration is also required on the effects of wet cupping therapy on stroke survivors, considering that wet cupping is a complex form of at least two kinds of interventions, namely, cupping and bloodletting puncture. In traditional Chinese medicine, bloodletting puncture without cupping is often performed, especially in stroke patients in the acute stage or with impaired consciousness, and a recent clinical trial has recently been published showing that bloodletting puncture could provide clinical benefits to stroke patients with disturbance of consciousness³⁸⁾. Further studies to compare and classify the effects
of dry cupping, bloodletting puncture, and their combined form, wet cupping are required. Generally, cupping therapy has been considered safe³³⁾, but AEs including anemia, infection, and scar formation have been reported^39,40). There have also been concerns that it might actually cause stroke^41). However, this study detected no serious AEs related to cupping therapy and
demonstrated that the incidence of AEs in the additional cupping group was not significantly higher than that in the noncupping control group. This is consistent with the suggestions in previous studies that cupping therapy is a relatively safe intervention under the condition that it is carefully performed by experienced practitioners⁴⁰⁾. However, considering that the meta-analysis
on the occurrence of AEs in this study was based on only two small trials and that most of the reviewed studies did not consider the safety profile of cupping therapy in the process of study design, or omitted the reporting of AEs in the articles, we are hesitant to draw definitive conclusions about the safety of cupping therapy here. In particular, considering that there have
been concerns^41-43) that cupping therapy performed on the neck area might cause arterial dissection by excessively raising the blood pressure of the carotid artery or vertebral artery that supplies cerebral circulation and eventually causes stroke, practitioners need to be careful not to induce excessive stress on the inside of the neck when performing cupping therapy in the neck area for stroke survivors.
This study has several limitations. First, despite our best efforts to secure as many relevant articles as possible, there may have been related trials that were not discovered by the search strategy in this study. We searched some databases based in Korea and China in addition to globally used core databases. This approach may have resulted in not identifying local publications in other regions, such as the Middle East or Africa, where cupping therapy has been used as a traditional intervention.
Second, there was a problem regarding the quantitative limitations of the included studies. Since there was no case in which the meta -analysis included more than 10 original trials, we could not construct a funnel plot to explore the existence of publication bias. Moreover, the scale of individual trials was too small. None of the trials had more than 100 participants per group.
Crucially, no studies had previously calculated the optimal sample size for adequate power. Third, the reporting quality of the included studies was low. Most studies did not clearly disclose how they corrected for the biases related to the random sequence generation, allocation concealment, dropout, and data selection. Most of them also omitted the reporting of AEs, as
mentioned above. These omissions in reporting deteriorated the overall quality of the methodology of each trial and consequently lowered the certainty of the evidence derived from this systematic review and meta-analysis.
Fourth, none of the included studies considered blinding. Some researchers have attempted to develop a sham or minimal cupping device as a control intervention for cupping therapy^44-46). However, no sham/minimal cupping device has been confirmed to be perfectly suitable for blinding patients or practitioners^44-46). Nevertheless, at least assessor blinding should have been ensured as a minimum measure to reduce detection bias. However, none of the included studies mentioned assessor blinding. Fifth, the underlying mechanisms of the therapeutic effects of cupping therapy in the context of stroke
has not been clearly determined. A previous systematic review⁶⁾ speculated that the benefit of cupping therapy for stroke rehabilitation may be due to the excretion of excess fluid and toxins and improvements in subcutaneous blood flow. To date, however, all of the hypotheses remain unclear.
Sixth, no conclusion was drawn about the influence of cupping therapy on critical outcomes directly related to stroke itself. In particular, as there are no long-term follow-up outcomes, the effects of cupping therapy on mortality, severe disability, and recurrence of stroke is still unexplored.
Finally, a large number of studies have adopted response rates as the main outcome measure instead of the internationally accepted standardized endpoints. This issue is one of the well-known chronic problems of RCTs dealing with cupping therapy³³⁾. It can be a factor that prevents readers worldwide from trusting and adequately understanding the study results.

Conclusion

The findings of this study demonstrated the potential of cupping therapy to be beneficial in managing a variety of complications in stroke survivors. In particular, wet cupping therapy as an add-on for stroke survivors receiving conventional
treatment provided significant benefits in improving upper limb motor function and spasticity, and these findings were supported by a moderate level of evidence. It was also found that cupping therapy did not significantly increase the occurrence
of AEs, although the level of supporting evidence was very low. However, considering that the overall quality of the methodology of the included studies was low, further large-scale RCTs with rigorous designs are warranted to draw definite conclusions on the effectiveness and safety of cupping therapy for stroke survivors. 

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