A Comprehensive Analysis of Conventional Acupuncture and Pharmacological Approaches for Cardiac Arrhythmias: An Umbrella Review

TL;DR

This study compares acupuncture and medication for treating heart rhythm disorders, finding acupuncture more effective for some types of arrhythmias.

Contribution

The study provides a comprehensive umbrella review comparing acupuncture and pharmacological treatments for cardiac arrhythmias.

Findings

Acupuncture significantly reduced ventricular premature beats more than medication.

Acupuncture showed a favorable safety profile with effectively managed adverse events.

Effectiveness of acupuncture varied across different types of arrhythmias.

Abstract

With a global incidence of approximately 3.4% and an annual mortality rate of 3.7 million, cardiac arrhythmias (CAs) are a pressing global health issue. Their increasing prevalence, especially among older people, is intensifying the challenge for health care systems worldwide. This study aims to compare the safety and effectiveness of acupuncture and pharmacological treatments for CAs, addressing critical gaps in understanding optimal therapeutic approaches. A search of PubMed, EMBASE, and the Cochrane database of systematic reviews was performed to identify data compiled through September 2023 for this umbrella review. Randomized controlled trials (RCTs) as the foundation for meta-analyses and peer-reviewed systematic reviews were the primary focus of the literature search. The Grading of Recommendations Assessment, Development, and Evaluation method was used to assess the overall certainty of the evidence, whereas AMSTAR 2 and the Cochrane Collaboration tool were used to evaluate the quality of the included reviews. Following a comprehensive review, three systematic analyses of 27 RCTs were integrated. Acupuncture led to a slightly greater reduction in the recurrence rate of paroxysmal supraventricular tachycardia (SVT) compared to standard pharmaceutical therapy (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.88–1.27; I2 = 56%; P = .55), although the difference was not statistically significant. In contrast, acupuncture significantly outperformed pharmacological treatment in the context of ventricular premature beats (VPBs) (RR, 1.16; 95 CI, 1.08–1.25; I2 = 0%; P < .0001). The reduction in paroxysmal atrial fibrillation (AF)/atrial flutter was increased with acupuncture, albeit without statistical significance (RR, 1.12; 95% CI, 0.88–1.42; I2 = 0%; P = .36). Acupuncture also led to a greater reduction in heart rate (HR) compared to pharmaceutical treatment despite notable heterogeneity and a lack of statistical significance (mean difference, −1.55; 95% CI, −41.37 to 38.28; I2 = 99%; P = .94). Adverse events were effectively managed, affirming the favorable safety profile of acupuncture. Our study suggests that acupuncture leads to a greater reduction in the recurrence rates of VPBs, AF, and atrial flutter but not significantly so in paroxysmal SVT or post-treatment HR. While promising for specific arrhythmias, the varying effectiveness of acupuncture underscores the need for further research and clinical assessment to determine its precise role and suitability in managing particular cardiac conditions.

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Introduction

Cardiac arrhythmias (CAs) refer to cardiac disorders marked by abnormal ventricular contractions.^1^ With a global incidence of approximately 3.4%, CAs contribute to an annual mortality rate of about 3.7 million.^2^ The increasing CA prevalence, especially among older people, poses a significant health care challenge. Effectively managing CAs is crucial due to their substantial impact on morbidity and mortality.^3^ Traditional therapies, encompassing anti-arrhythmic medications, surgical interventions, ablation, cardioversion, and medical devices, face limitations in efficacy and applicability and lead to notable adverse effects.^4,5^ While traditional CA care offers health benefits, it also incurs significant financial costs.^6^ Recognizing these limitations, there is a growing interest in exploring supplemental interventions that are both effective and cost-efficient while ensuring safety.^7^

The World Health Organization lists 31 symptoms, disorders, and diseases, including heart discomfort, arrhythmias, and hypertension, for which acupuncture has been studied extensively.^8^ Controlled research has shown acupuncture’s efficacy in treating various conditions,^9^ rooted in traditional Chinese medicine’s (TCM’s) historical use for palpitations, a common manifestation of arrhythmia.^10^ Current evidence supports acupuncture’s potential as a supplementary intervention for cardiovascular ailments, influencing cardiac rhythm through a neurological pathway that modulates sympathetic outflow.^11^ The neural mechanism forms the basis for acupuncture’s cardiovascular impacts, including blood pressure reduction, relief of myocardial ischemia, and—as demonstrated in this paper—the mitigation of ventricular arrhythmias associated with ischemia.^11^ Further research is needed to fully understand how acupuncture may reduce ischemia and arrhythmias, possibly by enhancing myocardial oxygen demand.

In the early 1990s, preliminary studies suggested that acupuncture may improve angina symptoms in individuals with ischemic heart disease, particularly those who are treatment-sensitive who show vasodilation during electroacupuncture.^12^ Experimental investigations on feline subjects with demand-induced ischemia instrumentation supported these clinical observations, revealing that acupuncture reduces myocardial ischemia by decreasing oxygen demand, particularly neutralizing increases in blood pressure during organ stimulation.^12^ The efficacy of acupuncture is closely linked to the precise choice of acupoints, a principle well acknowledged in TCM, where specific acupoints are recognized for distinct therapeutic advantages.^13–15^

Acupuncture significantly impacts therapeutic outcomes with its diverse components, such as acupoint selection, frequency, and needle retention. Yet, substantial variability in acupuncture parameters across clinical trials may lead to inconsistent results. Identifying optimal acupuncture parameters for CA management is crucial. CAs are commonly managed with anti-arrhythmic medications, such as β-blockers, calcium channel blockers, and sodium channel blockers. The choice between acupuncture and pharmacological intervention should consider patient-specific factors, including the type and severity of the arrhythmia, underlying medical conditions, and patient preferences.^1–5^ As an alternative therapy, acupuncture offers potential benefits, including minimizing adverse effects and promoting overall health.^3–5^ Controlled clinical trials are crucial to assess acupuncture’s efficacy in managing CAs and to establish its place alongside conventional pharmaceutical therapies. To address this, we performed an umbrella review of systematic reviews and meta-analyses meeting specified criteria. This study aims to compare acupuncture and pharmacological treatments, addressing safety and effectiveness concerns and offering practical recommendations for future clinical practices and trials in this field.

Methodology

This umbrella review of systematic reviews and meta-analyses was developed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane Collaboration Handbook guidelines.^16,17^

Search strategy

To ensure a comprehensive search, we systematically explored relevant literature databases, including PubMed, the Cochrane Library, Embase, Scopus, and the Web of Science. The search strategy incorporated an extensive set of keywords and Medical Subject Headings (MeSH) to guarantee the inclusivity of pertinent studies. Keywords included variations of “atrial fibrillation,” “AF,” “acupuncture,” “traditional Chinese medicine,” “needle therapy,” “pharmacological treatment,” “drug therapy,” “medications,” “antiarrhythmic agents,” “rhythm control,” “cardioversion,” “anticoagulation,” and “randomized controlled trials.” Boolean operators “AND” and “OR” were strategically employed to effectively refine and broaden the search; for instance, “atrial fibrillation AND acupuncture AND pharmacological treatment” narrowed the focus to studies comparing these two interventions, while “atrial fibrillation OR AF OR rhythm control” was used to expand the search within each concept to ensure a comprehensive search. The detailed search strategy is summarized in Supplementary Table S1. The literature search was conducted independently by two researchers to avoid any selection bias. Consensus resolved disagreements, but a third researcher was consulted if discrepancies persisted.

Study inclusion and exclusion criteria

Inclusion criteria

This umbrella review encompassed high-quality systematic reviews and meta-analyses that have examined the comparative effectiveness of acupuncture and pharmacological interventions in treating atrial fibrillation (AF) and included studies focused on adult participants aged ≥18 years diagnosed with AF. Reviews that investigated acupuncture as a treatment modality for AF were included. Additionally, studies that assessed the effectiveness of pharmacological interventions for AF, such as medications used for rhythm control, rate control, and anticoagulation, were also incorporated to facilitate a comprehensive comparative analysis. Separately, we also included meta-analyses directly comparing the efficacy and safety of acupuncture with pharmacological interventions for treating AF. Finally, we considered studies that reported relevant clinical outcomes, including but not limited to rhythm control (eg, conversion to sinus rhythm), rate control (eg, heart rate [HR] management), quality-of-life measures, safety, adverse events (AEs) associated with interventions, and cardiovascular events like stroke or myocardial infarction.

Exclusion criteria

Primary studies, conference abstracts, letters, editorials, and reviews not meeting the systematic review and meta-analysis criteria were excluded. Reviews on pediatric populations (participants <18 years old) or animal models were excluded. Studies examining interventions unrelated to acupuncture or pharmacological treatments for AF were not included. Reviews that did not directly compare acupuncture with pharmacological interventions in the context of AF were excluded. Studies lacking relevant clinical outcomes or reporting incomplete data were not considered for this umbrella review.

Data extraction

Key data elements extracted included publication details (title, authors, publication year, and source), study characteristics (design, inclusion criteria, number of primary studies included), participant characteristics (age range, sex distribution), descriptions of acupuncture and pharmacological interventions (techniques, frequency, duration, medications, doses, administration), outcome measures (mortality, reduction in the recurrence of supraventricular tachycardia [SVT], reduction in ventricular premature beat [VPB] burden, reduction in the paroxysms of AF/atrial flutter, and mean HR post-treatment), effect measures used in the comparisons (eg, risk ratios [RRs], mean differences [MDs]), and details of the quality assessment methodology and results.

Assessment of risk of bias

Two researchers independently rated the methodological quality of the included reviews and meta-analyses using the AMSTAR 2 tool. AMSTAR 2 is an instrument designed to critically assess the risk of bias in systematic reviews that consists of 16 domains referring to relevant methodological aspects, which are answered with a “yes,” “no,” “cannot answer,” or “partial yes.” The overall quality of the studies was categorized as follows: high, moderate, low, or critically low.^18^ Moreover, we assessed the risk-of-bias (quality) of the RCTs included in the individual meta-analysis using the Cochrane Collaboration risk-of-bias tool, which evaluates eight potential sources of bias, including random sequence generation, allocation concealment, blinding of participants, evaluator and outcome assessments, incomplete outcome data, missing data, and other.^19^

The certainty of evidence and strength of recommendations from meta-analyses were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method.^20^ This tool provides a system rate with four categories, as follows: “high” when the systematic review or meta-analysis includes at least two high-quality primary studies, “moderate” when it has at least one high-quality or two moderate-quality primary studies, “low” when it contains only moderate-quality and/or inconsistent results studies, and “very low” when no medium- to high-quality studies were identified on this topic. Our starting point was “high,” and this grading decreased when we detected risk of bias, inconsistency of results (ie, I^2^ > 50%), indirectness of evidence (ie, differences in intervention), imprecision (ie, 95% confidence interval [CI] includes 1.0), or publication bias (asymmetry in funnel plot). Additionally, the rating was increased if there was a significant intervention effect, in case of a dose–response relationship, or if all plausible biases would decrease the magnitude of the intervention effect.^20^ Two researchers independently conducted the GRADE assessment with discussion and agreement for discrepancies.

Statistical analysis

All statistical analyses and power calculations were performed using the Comprehensive Meta-analysis Software (CMA) version 4 (Biostat, Englewood, NJ, USA) and Review Manager version 5.4.1 (Cochrane, England, UK). We recalculated the effect sizes as RR values for each categorical outcome with corresponding 95% CIs using the DerSimonian and Laird random-effects model. For continuous data, we calculated the MD. P < .05 was considered statistically significant in two-sided tests. The heterogeneity between study associations was assessed using the I^2^ statistic.^21^ Sensitivity analyses were conducted to evaluate the robustness of summary estimates and to detect whether any individual study accounted for a large proportion of heterogeneity. Egger’s regression asymmetry test was used to calculate the evidence of small-study effects.^22^ Therefore, P < .05 was considered to indicate proof of small-study effects. We also assessed “P-hacking”^23^ and publication bias by visualizing funnel plots, trim, and fill analysis.

Ethical considerations

As this umbrella review relied solely on previously published systematic reviews and meta-analyses, it did not involve collecting or analyzing primary data from human participants. Therefore, this study did not require ethical review board approval or collection of patient consent.

Results

Study selection

A total of 30 systematic reviews and meta-analyses were initially identified, with duplicate entries being excluded. After comprehensively examining complete texts, we ultimately integrated three systematic reviews and meta-analyses,^24–26^ which collectively included data from 27 randomized controlled trials (RCTs).^27–51^ Table 1 provides a concise overview of the critical attributes of the meta-analyses incorporated in this study.

Risk of bias of included studies

The AMSTAR 2 methodological quality ratings for the three systematic reviews and meta-analyses are presented in Supplementary Table S2. All three studies obtained a moderate-quality grade. According to the findings presented in Supplementary Table S3, the GRADE assessment revealed that the reviews included in our study exhibited a varying degree of certainty, ranging from moderate to high. The quality assessment of individual RCTs was done using the Cochrane risk-of-bias tool, which showed trials had a moderate-to-low risk of bias, as displayed in Supplementary Figure S1.

Synthesis of results

Efficacy outcomes

The efficacy outcomes included a reduction in the recurrence rates of SVT, VPBs, and AF/atrial flutter in response to treatment as well as post-treatment HR.

Paroxysmal supraventricular tachycardia

The study incorporated three systematic reviews and meta-analyses, each providing data on paroxysmal SVT’s response to treatment. The pooled analysis demonstrated that acupuncture was associated with a marginally greater reduction in the rate of recurrence of paroxysmal SVT when compared to standard pharmaceutical therapy (relative risk, 1.06; 95% CI, 0.88–1.27; I^2^ = 56%; P = .55), as depicted in Figure 1. Nevertheless, it is crucial to acknowledge that the above findings did not achieve statistical significance, as indicated by P = .55. Additionally, the 95% CI for the relative risk encompassed the null value, denoted as 1.

Ventricular premature beats

Data on VPBs’ response to treatment were available in two of the three studies. A combined analysis indicated a significantly greater reduction in the VPB burden associated with acupuncture treatment when compared to pharmacological therapy (relative risk, 1.16; 95% CI, 1.08–1.25), with no significant heterogeneity (I^2^ = 0%) and a highly significant P value (P < .0001), as illustrated in Figure 2.

Atrial fibrillation/atrial flutter

Among the three studies, data regarding the response of AF/atrial flutter to treatment were available in two. The combined analysis indicated that acupuncture treatment is linked to a greater rate of reduction in the paroxysms of AF/atrial flutter when compared to pharmacological therapy (relative risk, 1.12; 95% CI, 0.88–1.42), with no substantial heterogeneity (I^2^ = 0%) and P = .36, as depicted in Figure 3. However, it is worth noting that these findings did not reach statistical significance, as suggested by the non-significant P value.

Post-treatment HR

Two studies provided data regarding HR post-treatment. The comprehensive analysis revealed that acupuncture therapy resulted in a greater decrease in HR toward normality in comparison to pharmaceutical treatment (MD, −1.55; 95% CI, −41.37 to 38.28). However, there was a notably high level of heterogeneity (I^2^ = 99%), and P = .94 indicated that these results did not achieve statistical significance, as shown in Figure 4. The high heterogeneity observed in this analysis may be attributed to several potential factors. These factors could include patient characteristics, differences in acupuncture techniques and protocols, diverse pharmacological treatments used in the control groups, and inconsistencies in outcome measurement and reporting across the studies included in the analysis. These above factors could have had a role in the extensive variability of outcomes, posing a significant challenge in formulating definitive conclusions based on the aggregated study.

Safety outcomes

Four trials reported AEs. The study by Zhang et al.^47^ showed that the acupuncture group exhibited no AEs. However, in the amiodarone group, one patient experienced hypotension, and two patients experienced episodes of vomiting. These AEs were effectively addressed with symptomatic therapy, allowing the patients to continue participating in the trial. Significantly, a greater incidence of AEs was reported in the cohort receiving pharmaceutical treatment compared to the cohort receiving acupuncture.

Two previous trials^32,45^ documented adverse outcomes linked to amiodarone administration by oral or intravenous routes. These AEs encompassed many symptoms, including loss of appetite (anorexia), rapid HR (sinus tachycardia), impairment in the electrical conduction system of the heart (atrioventricular block), low blood pressure (systolic blood pressure of <90 mmHg), and the act of expelling stomach contents forcefully (vomiting). In one particular investigation,^44^ it was seen that acupuncture as a standalone intervention did not result in any unfavorable occurrences like bleeding, hematoma, infection, pain, or vasovagal reactions. However, a separate study^45^ documented events of red swelling and pruritic skin associated with using catgut at acupoints.

P-hacking, publication bias, and small-study effect

The absence of evidence of P-hacking in our research implies that the results were not subject to manipulation to get a predetermined outcome. Notably, our assessment of publication bias was limited to more than one of the outcomes. This constraint occurs because a minimum of three studies are necessary to conduct a comprehensive analysis using a funnel plot. We could not thoroughly assess publication bias for the remaining outcomes, as each of them was only reported by two studies. In examining the reduction in the recurrence of paroxysmal SVT, we conducted a thorough analysis using sufficient studies to facilitate a funnel plot analysis. Our findings revealed that the funnel plot exhibited a symmetrical distribution of data points. The observed symmetry in the data implies the absence of publication bias, as demonstrated in Supplementary Figure S2. We also assessed small-study effects using Egger’s regression asymmetry test. The findings of our investigation revealed P values (.639) that were >.05, suggesting a lack of substantial evidence for small-study effects.

Discussion

CAs are marked by irregular heartbeats, and types include premature beats, SVT, ventricular arrhythmia, conduction block, and bradyarrhythmia.^24^ Acupuncture, rooted in TCM, is gaining attention for its potential physiological effects on arrhythmias. Recent studies suggest its impact on the autonomic nervous system, modulating sympathetic and parasympathetic functions.^25^ Focused on specific acupoints, acupuncture activates brain circuits, particularly in the hypothalamus, midbrain, and medullary networks, regulating sympathetic outflow. This neurological regulation influences blood pressure reduction, relief from myocardial ischemia, and decreased ventricular arrhythmias linked to ischemic events.^25^ In Western medicine, Neiguan acupoint acupuncture has gained recognition for managing symptoms during transcatheter arterial chemotherapy. Experimental evidence indicates its effectiveness in alleviating palpitations and chest tension, reducing plasma endothelin levels, and modifying electrocardiographic signs related to myocardial ischemia.^25^ Bilateral acupuncture at Neiguan points is suggested to modulate the autonomic nervous system by influencing the firing rate of the amygdala, highlighting its potential anti-arrhythmic effects.^24,25^ Our study covered efficacy and safety measures for paroxysmal SVT, VPBs, AF/atrial flutter, post-treatment HR, and AEs.

The recurrence rate of paroxysmal SVT has not substantially improved with acupuncture compared to standard medical treatments.^24,25^ However, a study on acupuncture’s influence on HR variability, a metric tied to cardiovascular well-being, showed positive outcomes.^51^ While acupuncture may offer relaxation and tension relief, it should not replace primary interventions for severe cardiovascular issues, such as SVT.^25,26,51^ Regarding VPBs, Ning et al. found that combining acupuncture with TCM significantly reduced premature beats within 24 h.^52^ The study reported a standard MD of −10.55 (95% CI, −14.61 to −6.49), with a highly significant P value (<.00001). This suggests a potential therapeutic advantage of integrating acupuncture and TCM in treating the examined condition.

The use of early acupuncture for AF initially showed superior efficacy in restoring sinus rhythm when compared to using anti-arrhythmic medications. However, evolving therapeutic protocols led to a reduction in acupuncture’s anti-arrhythmic advantages, coupled with an increase in extracardiac adverse effects from the anti-arrhythmics. The combined use of anti-arrhythmics and acupuncture emerged to mitigate side effects and enhance overall effectiveness. In a study by Liu et al.,^24^ traditional acupuncture alone did not significantly surpass oral or intravenous amiodarone. Conversely, combining intravenous deslanoside with conventional acupuncture, as per Han et al.,^28^ showed a more pronounced augmenting effect on the response rate. The study by Lomuscio et al.^29^ supported conventional acupuncture as a standalone therapy, reducing AF recurrence post-electrical conversion for up to 3 months. However, this impact diminished at 6- and 9-month intervals. The investigation by Xu et al.,^31^ comparing acupuncture and amiodarone in paroxysmal AF, recorded significantly higher rates of sinus rhythm restoration and shorter cardioversion times in the acupuncture group.

Our investigation revealed that, compared to medication, acupuncture therapy significantly reduces HR, bringing it closer to the normal range. Li et al.^30^ documented a substantial decrease in HR (MD, −21.84; 95% CI, −27.21 to −16.47) during a 30-min acupuncture session within the conventional acupuncture group. Additionally, the study by Dong et al.^27^ showed no notable improvement in the response rate of paroxysmal SVT with a single 20-min acupuncture session in the conventional acupuncture-alone group compared to a group receiving intravenous propafenone (RR, 0.88; 95% CI, 0.70–1.09).

Our research holds a distinct advantage over individual studies as it systematically compiled and amalgamated data from multiple systematic reviews and meta-analyses about a specific topic. This approach provides a comprehensive and in-depth overview of the existing body of research on the subject. Nonetheless, our study is subject to certain limitations. First, this review encompassed only three studies, each yielding a limited number of baseline data (eg, acupuncture approach, treated sites, cycles of treatments, and types of needles) and outcomes. Consequently, further investigation is necessary to establish conclusions supported by a broader range of evidence, as quantification or measurement of neurohormonal markers, inflammation markers, and catecholamines after acupuncture were not examined to determine its effects on the heart and the mechanisms by which it might work, owing to the limited number of studies. Second, substantial heterogeneity in specific outcomes can be attributed to the diverse methodologies, inclusion criteria, and outcome measures adopted across the various systematic reviews. Third, there exists the possibility of double counting and inflation of the evidence base owing to the inclusion of certain primary studies in multiple systematic reviews. Finally, it is important to note that our study relies on synthesizing pre-existing data instead of generating new data.

Conclusion

In conclusion, our study demonstrates that acupuncture is associated with a heightened reduction in the recurrence rates of VPBs, AF, and atrial flutter. However, it does not significantly impact the paroxysmal SVT recurrence rate or post-treatment HR. It is worth noting that, while acupuncture shows promise for specific arrhythmias, its effectiveness may vary across different conditions. For patients with VPBs, AF, or atrial flutter, considering acupuncture as a complementary therapeutic option could be beneficial. Nevertheless, further research and clinical assessment are essential to determine its precise role and suitability for specific CAs.