Key Takeaways From the AHA Statement on CAM in HF

The recently released scientific statement on complementary and alternative medicines (CAM) in the management of patients with heart failure (HF) from the American Heart Association (AHA) provides a much-needed evidence-based review of the role of CAM for patients with HF — including potential areas of harm. Although CAM is commonly used worldwide to treat a plethora of medical conditions, most therapies have not been rigorously studied in clinical trials and generally remain unregulated. For this reason, it is essential to advise patients on the safety and appropriateness of using CAM as an adjunct to conventional, guideline-directed HF therapies. Here, we highlight some of the key points from the AHA statement.

Oversight, Safety, Communication

CAM broadly encompasses biological-based (eg, botanicals, extracts, vitamins, mineral supplements) and non–biological-based (eg, energy therapies, manipulative and body-based methods, mind-body medicine) treatments. Clinicians should be particularly aware of biological-based treatments because of the potential for drug interactions or direct toxicity with guideline-directed medications and the lack of direct federal oversight in the manufacturing process. Although the US Pharmacopeia (USP) has established quality assurance standards, not all CAM manufacturers achieve these standards or obtain the optional USP-verified designation.

Even though the US Food and Drug Administration (FDA) does not oversee the manufacture of CAM products, any adverse events from these therapies should be reported to the FDA's MedWatch program. Some clinicians may not be aware that this program also applies to alternative medicine products. Furthermore, evaluating the causality of adverse reactions can be challenging because patients with HF typically have complex medical conditions requiring several medications.

Some clinicians may not ask their patients about CAM. To better identify adverse effects associated with alternative therapies, in its statement, the AHA recommends that clinicians make it standard practice to ask patients about their use of any CAM and other wellness therapies.

Shared decision-making is especially important to establishing trust between patients and clinicians. This trust cannot develop if a clinician dismisses or ignores a patient's preferences or interest in alternative treatments. As the AHA statement emphasizes, although CAM should never replace standard guideline-directed and evidenced-based HF therapies, clinicians should discuss with interested patients when CAM therapy can be safely considered in conjunction with conventional treatment.

The AHA statement highlights several important considerations when discussing CAM therapy with patients. Along with safety concerns, clinicians should address cost considerations since CAM, as an adjunctive therapy, will increase overall treatment cost. Patients should be informed that the cost of CAM products should not become a barrier to initiating and titrating HF guideline-directed therapies. If this does become an issue, there should be a follow-up discussion and patient education to refocus and guide decision-making. As often is the case, a multidisciplinary approach that includes a clinical pharmacist is valuable to help improve management and safety.

Potentially Beneficial Treatments

The AHA statement includes a comprehensive list of commonly used CAM and wellness approaches, summarizing the potential benefits, risks, and unknown safety in patients with HF.

Omega-3 polyunsaturated fatty acids (PUFA) may benefit patients with HF by potentially improving left ventricular ejection fraction (LVEF) and reducing mortality and cardiovascular hospitalizations. The most common side effects associated with PUFA are gastrointestinal symptoms, including abdominal pain and diarrhea. Although PUFA in moderate doses is generally considered safe, data from two large trials show an increased incidence of atrial fibrillation in patients taking > 2 g/d of a carboxylic acid formulation of omega-3 fatty acids or an omega-3 fatty acid preparation consisting of purified EPA (icosapent ethyl), respectively.

Coenzyme Q10 (CoQ10) and its reduced and oxidized forms, ubiquinone and ubiquinol, respectively, may reduce major cardiovascular events and all-cause mortality in patients with HF. Small studies have shown CoQ10 to modestly improve LVEF and quality of life in patients with HF. Owing to the need for larger randomized studies, the value of CoQ10 for HF is still uncertain.

Tai chi and yoga are generally well tolerated and safe for patients with HF, posing no significant harm and having no known interactions with HF therapies. As summarized in the AHA statement, it is believed that these low-intensity forms of exercise exert a beneficial effect by increasing parasympathetic activity and decreasing sympathetic activity. Tai chi has demonstrated improved mood, quality of life in patients with chronic HF. Although patient enrollment in dedicated tai chi and yoga trials has been lower than enrollment in other CAM-HF trials, they show promise for their exercise and rehabilitative benefits.

Thiamine (vitamin B1) and vitamin D may benefit patients with HF; however the evidence is mixed and remains inconclusive. Although small studies found that thiamine supplementation was associated with a small improvement in LVEF in patients with HF, one trial found no difference in quality of life, 6-minute walk, N-terminal pro-B type natriuretic peptide, or LVEF after 6 months. Similarly, study findings on the role of vitamin D in HF are variable regarding the ability to lower inflammatory markers and improve LV function, mortality, and quality of life. Notably, the VITAL-HF trial found that vitamin D3 supplements did not significantly reduce hospitalization in patients with a first event of HF. For these reasons, thiamine and vitamin D supplementation are only recommended for patients with deficiency.

Agents That Can Be Harmful

Some CAM therapies listed in the AHA statement, including gossypol, grapefruit juice, licorice and its derivatives, cardiac glycoside-containing plants, and vitamin E, are potentially harmful to patients with HF and should be used cautiously.

Gossypol, a supplement derived from the cotton plant, may cause hypokalemia and circulatory issues.

Owing to its inhibition of cytochrome P450 3A4, grapefruit juice may alter cardiac drug metabolism, leading to increased bioavailability. As summarized in the AHA statement, grapefruit juice consumption is associated with increased serum levels of carvedilol and decreased effectiveness of losartan. There is also an increased risk for QT prolongation when grapefruit juice is taken with amiodarone, dofetilide, and sotalol. Patients who have HF and atrial fibrillation should not consume grapefruit or grapefruit juice with cardiac medications owing to this potential increased risk for QT prolongation.

Licorice root, taken by some patients, may lead to mineralocorticoid excess and cause hypertension, hypokalemia (resulting in arrhythmia), sodium retention, and cardiac arrest. Patients taking mineralocorticoid receptor agonists (eg, spironolactone) and adults age 40 years or older are at increased risk for adverse effects and should use caution when consuming licorice root. According to an FDA consumer alert, licorice consumption should be limited to not more than 2 oz per day over a 2-week period.

Cardiac glycoside-containing plants (eg, lily of the valley, oleander, strophanthus, ouabain) have been used to treat mild HF and atrial fibrillation. Accidental poisoning is common with cardiac glycoside use owing to the narrow therapeutic index. Because hypokalemia can increase the effects of cardiac glycosides, they should not be taken with loop diuretics and corticosteroids.

Vitamin E (alpha-tocopherol) may increase the risk of incident HF and HF hospitalization. In the HOPE and HOPE-TOO trials, patients who were randomly assigned ≥ 400 IU of vitamin E daily showed an increased risk for incident HF and related hospitalization. The AHA statement suggests consumption of vitamin E be limited to <400 U/day.

Therapies With Uncertain Safety Profiles

The efficacy and safety of several CAM therapies have been shown to be inconclusive. The effect of alcohol consumption on HF has not been studied in large-scale randomized trials. Observational data suggest low to moderate alcohol use, defined by the US Dietary Guidelines for Americans as no more than 2 drinks per day for men and no more than 1 drink per day for women, may reduce incident HF. However, routine use or abuse can lead to cardiomyopathies.

A review of the data indicates that moderate caffeine consumption is safe; however, excessive consumption (> 500 mg within 5 hours) may increase the risk for arrhythmias. One study found that caffeinated coffee intake reduced the risk for future HF, whereas another showed neutral effects.

Evidence for hawthorn use in HF is mixed, showing possible benefits to cardiac contractility and vasodilation, though drug interactions remain a concern. Use of hawthorn with digoxin should be avoided.

Some studies have shown benefits of L-arginine, including improved endothelium-dependent vasodilation, LV structure and function, quality of life, and New York Heart Association class. However, L-arginine should be avoided in patients who have had acute myocardial infarction because randomized controlled trial data have shown it to be associated with an increased risk for mortality.

Practice Tips

During office visits, clinicians should ask patients about their use of CAM and other adjunctive wellness approaches and document these in the electronic medical record. The discussion should be open and nonjudgmental, encouraging future disclosure of any intent to initiate or continue using a CAM product. Patients should be informed of risks associated with potentially harmful CAM products, including those with an uncertain safety profile. For patients who are using potentially beneficial CAM therapies, suggest that they look for the USP verification mark on product packaging or use the USP website to determine whether a product meets good manufacturing standards.

When discussing CAM with patients, be sure to highlight uncertainty regarding a product's efficacy and safety. Many labels contain phrases to encourage purchase (eg, "for serious heart support," "super supplement)."

Although the new AHA statement provides guidance on the role of CAM in patients with HF, there are still evidence gaps and lack of awareness about these therapies. There is a pressing need for additional mechanistic studies and well-designed, sufficiently powered randomized and pragmatic clinical trials to evaluate the safety, efficacy, and risks of CAM in patients with HF. Future efforts should also focus on continued education and research to achieve the goal of improving patient outcomes.

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