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