A randomized controlled trial of acupuncture in stable ischemic heart disease patients,☆☆

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Abstract

Background

Heart rate variability (HRV) is reduced in stable ischemic heart disease (SIHD) patients and is associated with sudden cardiac death (SCD). We evaluated the impact of traditional acupuncture (TA) on cardiac autonomic function measured by HRV in SIHD patients.

Methods

We conducted a randomized controlled study of TA, sham acupuncture (SA), and waiting control (WC) in 151 SIHD subjects. The TA group received needle insertion at acupuncture sites, the SA group received a sham at non-acupuncture sites, while the WC group received nothing. The TA and SA groups received 3 treatments/week for 12 weeks. 24-Hour, mental arithmetic stress, and cold pressor (COP) HRV was collected at entry and exit, along with BP, lipids, insulin resistance, hs-CRP, salivary cortisol, peripheral endothelial function by tonometry (PAT), and psychosocial variables.

Results

Mean age was 63 ± 10; 50% had prior myocardial infarction. Comparison of WC and SA groups demonstrated differences consistent with the unblinded WC status; therefore by design, the control groups were not merged. Exit mental stress HRV was higher in TA vs. SA for markers of parasympathetic tone (p  0.025), including a 17% higher vagal activity (p = 0.008). There were no differences in exit 24-hour or COP HRV, BP, lipids, insulin resistance, hs-CRP, salivary cortisol, PAT, or psychosocial variables.

Conclusions

TA results in intermediate effects on autonomic function in SIHD patients. TA effect on HRV may be clinically relevant and should be explored further. These data document feasibility and provide sample size estimation for a clinical trial of TA in SIHD patients for the prevention of SCD.

Condensed abstract

We conducted a randomized, single-blind trial of traditional acupuncture (TA) vs. sham acupuncture (SA) vs waiting control (WC) in stable ischemic heart disease (SIHD) patients to evaluate cardiac autonomic function measured by heart rate variability (HRV). Exit mental stress HRV was higher in the TA compared to SA group for time and frequency domain markers of parasympathetic tone (all p  0.025), including a 17% higher vagal activity (p = 0.008). These data document feasibility and provide sample size estimation for an outcome-based clinical trial of TA in SIHD patients for the prevention of sudden cardiac death.

Introduction

Sudden cardiac death (SCD) is a significant problem in patients with stable ischemic heart disease (SIHD), and accounts for 30 to 50% of deaths in this group (~ 150,000 deaths annually) despite the identification and treatment of their disease [1], [2], [3]. Risk factors for SCD are similar to those for SIHD, and include cigarette smoking, hypertension, physical inactivity, hyperlipidemia, and diabetes [4], [5]. The mechanism of SCD in SIHD patients is predominantly arrhythmic, and involves the cardiac autonomic nervous system (ANS) [6]. Heart rate variability (HRV), a measure of cardiac ANS function, is reduced in patients with SIHD and predictive of arrhythmic SCD [7]. Cardiac arrhythmias have been implicated both as a risk factor and an etiology for SCD, suggesting that alteration of cardiac ANS tone may provide an opportunity for reducing acute cardiac events and SCD.

Traditional acupuncture (TA) is a complementary and alternative medicine (CAM) practice with documented beneficial effects on the cardiovascular system. For example, the TA technique has been shown to significantly reduce arrhythmias [8], hypertension in an animal model [9], mental stress in humans [10], and angina pectoris in SIHD patients [11]. These effects are consistent with the hypothesis that the TA technique causes autonomic remodeling, likely by reducing sympathetic and increasing parasympathetic activity.

We undertook a randomized, controlled trial of 12 weeks of TA compared to sham acupuncture (SA) and waiting control (WC) in 151 SIHD patients with the primary outcome of cardiac autonomic function measured by HRV. We also measured the secondary outcomes of blood pressure, lipoprotein profile, and insulin resistance, salivary cortisol, vascular inflammation, endothelial function measured by peripheral arterial tonometry (PAT), and psychosocial variables.

Section snippets

Patient population

Inclusion criteria: women and men aged > 18 years, with SIHD documented by prior myocardial infarction, coronary angiography, angioplasty, or coronary bypass surgery. Exclusion criteria: 1. unstable acute coronary syndrome; 2. congestive heart failure > New York Heart Association class III; 3. renal failure; 4. acute myocardial infarction in the preceding 3 months; 5. atrial fibrillation or a predominantly paced rhythm, significant conduction system disease, or automatic internal defibrillator; 6.

Results

Among the 151 patients enrolled, 131 (87%) subjects completed the study. The primary reason for subject withdrawal was time commitment and inability to take time off from work or unrelated, non-cardiac illness. The Acupuncture Delivery Protocol TA and SA were well-tolerated and there were no adverse side effects. The subject study flow is depicted in Fig. 2.

By design, the WC group served as a second control group for the purpose of detecting a potential placebo effect in the SA group.

Discussion

The current study results demonstrate that 12 weeks of TA resulted in significantly higher HRV compared to SA. The physiological effects were accomplished without changes in traditional risk factors or medication changes. Both time and frequency domain components of HRV indicative of parasympathetic activity were significantly higher at exit with TA vs. SA, suggesting that the observed effect was reasonably robust. The magnitude of exit SDNN difference between TA vs. SA may be clinically

Limitations

Our population may not be representative of the general SIHD population, as it is well documented that rates of optimal medical management achievement in non-selected SIHD populations [66], [67], [68], [69] are below that observed in our study subjects. We used a predictor of sudden cardiac death risk (HRV) that is used as an outcome in clinical trials [37], [70]; and while a significant beneficial effect was observed in HRV as hypothesized, this may have been minimized by the involvement in a

Implications

We studied TA in a blinded, randomized fashion, with a practical sham technique. Trials to study alternative and complimentary techniques are difficult due to various problems inherent in the nature of this type of study, however, given the rise in the use of alternative and complimentary techniques such as acupuncture in United States, our work sheds light into the practical and possibly beneficial use of acupuncture in optimally-treated, SIHD patients. Given acupuncture's beneficial impact on

Conclusions

Our current trial results demonstrate that 12 weeks of TA compared to SA has intermediate effects in cardiac autonomic modulation measured by HRV in SIHD patients. The TA magnitude of benefit on HRV may be clinically relevant and should be explored further. These data document feasibility and provide sample size estimation for a sudden cardiac death outcome clinical trial of sympatho-vagal modulation using TA in subjects at high risk for sudden cardiac death.

The following is the supplementary

Conflict of interest

Full disclosures: Mehta: Research support – Gilead, General Electric, NIH, CTSI. Lectures (paid to CSMC) – Medical Education Speakers Network; Minissian: Research support – Gilead; Shufelt: Research support - Gilead; Bairey Merz: CME Lectures (paid to CSMC) – Mayo Foundation, Bryn Mawr, Practice Point Communications, Allegheny General Hospital, Gilead (grant review committee), Duke, Japanese Circ Society, UCSF, Vox Media, Emory, PCNA, Kaiser Permanente, Garden State, AHA. Honorarium and

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    This work was supported by National Institutes of Health grants 5R01AT1482 (National Center for Complementary and Alternative Medicine) and K23HL105787 (National Heart, Lung, and Blood Institute), GCRC grant MO1-RR00425 from the National Center for Research Resources which is now the National Center for Advancing Translational Sciences (UL1TR000124, UL1RR033176), and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey, the Women’s Guild of Cedars-Sinai Medical Center, the Society for Women’s Health Research (SWHR), Washington, D.C., the Edythe L. Broad Women’s Heart Research Fellowship, the Barbra Streisand Women’s Cardiovascular Research and Education Program, and the Linda Joy Pollin Women’s Heart Health Program, Cedars-Sinai Medical Center, Los Angeles, CA. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, or the National Institutes of Health.

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    ClinicalTrials.gov Identifier: NCT00570024.

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