Use of Hawthorn for Mild Congestive Heart Failure
By Howell Sasser, PhD
Dr. Sasser is Director, Research Epidemiology, R. Stuart Dickson Institute for Health Studies, Carolinas HealthCare System, Charlotte, NC; he reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.
| Table | |
| NYHA classifications for congestive heart failure | |
| Class I |
Patients with no limitation of activities; they suffer no symptoms from ordinary activities. |
| Class II | Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion. |
| Class III | Patients with marked limitation of activity; they are comfortable only at rest. |
| Class IV | Patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest. |
Congestive heart failure (chf) is a chronic, usu-ally progressive condition that has a major impact on patients’ quality of life and life expectancy. Small exertions—even walking a short distance on a flat surface—can be extremely tiring. Edema of the lower extremities can be painful and require prolonged elevation and the use of compression garments. Most critically, the long-term stress of the body’s strategies to compensate for reduced cardiac efficiency—hypertension and accelerated heart rate—creates a vicious cycle that typically ends in progressive clinical deterioration and death.
In Europe and the
United States, the severity of CHF is classified according to the New
York Heart Association’s four-stage system (i.e., NYHA I-IV) (see
Table). The stages are defined practically, by the degree to which a
patient’s normal activity is limited by CHF. It is noteworthy that this
system separates the impact of disease from underlying physiologic
functioning. As a consequence, many studies of CHF interventions focus
on practical outcome measures such as exercise tolerance or dyspnea,
rather than more physiologic factors such as ejection fraction
(EF).
Treatments for CHF typically seek either to reduce the burden on the
heart, or to shore up the heart’s functional capacity. Given the
changeable nature of the disease, the frequency of comorbid diseases
(diabetes, renal disease, essential hypertension) in CHF patients, and
the necessity of poly-drug therapy to aggressively meet and maintain
clinical targets, CHF patients typically require relatively intensive
case management. This
need is only heightened by the potential for drug interactions and
adverse reactions to agents that should be carefully titrated (i.e.,
digoxin, ACE inhibitors, beta blockers).
Pharmacology
Hawthorn is an herbal remedy frequently used in traditional Chinese medicine and by European naturo-paths and homeopaths to treat a variety of conditions, including the milder stages of CHF.1 Preparations are derived from the fruit, leaves, and flowers of trees and shrubs of the genus Cratægus. Consumption by patients may be in the form of pills, tea, extract, or whole dried fruit. Among the key constituents are flavonoids and oligomeric proanthocyanidins (OPC), each of which is present in varying amounts in different parts of the plant.2 Hawthorn extracts are often formulated to contain standard amounts of the various constituents. A compound called WS 1442, among the most commonly used in clinical studies, is standardized to 18.8% OPC.3
Studies of the effect of hawthorn have focused on whole-plant extract, the flavonoid and OPC fractions, and individual components. Information on the pharmacodynamics of hawthorn compounds is speculative at best, and animal studies are the source of most of the theoretical data to date. There is some evidence that hawthorn may act through its effect on cyclic AMP, altering the sodium-calcium balance in cardiac tissue, as do the prescription inotropes.4 Another possible mechanism is through induction of hypotension, mediated by endothelium-dependent arterial relaxation.5 A third potential means of action involves hawthorn’s antioxidant and nitric oxide (NO) synthesis-enhancing properties.6 These would have the effect of reducing cardiac ischemia, thus improving myocardial efficiency.
(Note: A limitation in assessing the relative merits of these hypotheses, as well as the clinical studies of hawthorn preparations, is that much of the research to date has been conducted outside the United States, and has been reported in non-English-language journals [some with English abstracts] that are difficult to obtain in this country.)
Clinical Evidence
The possibility that hawthorn might be effective in reducing symptoms of mild CHF is especially appealing. Early treatment of the disease is often deferred or used to a suboptimal extent because of the side effects of many of the drugs currently in use. If another agent that combined similar clinical results with fewer side effects were available, better preservation of routine functioning might be possible for a greater number of patients and for a longer time.
The best available evidence of clinical efficacy is a meta-analysis published in 2003 by Pittler et al.3 It included results from eight randomized trials that enrolled a total of 632 patients. With one exception (see Tauchert below) participants had NYHA Class I or II heart failure. Most studies were of short duration (range, 3-16 weeks), and all but one used WS 1442 in daily doses ranging from 160 mg to 1,800 mg. Common study endpoints were maximal workload in watts (W) (four studies, 310 patients) and pressure-heart rate product (defined as units of systolic blood pressure [mm Hg] multiplied by heart rate per minute, the quantity then divided by 100) (six studies, 264 patients). In most studies, participants’ use of other medications was not restricted, and typically included a number of other agents that might influence CHF symptoms. The result of the meta-analysis showed a significant improvement in maximal workload among patients receiving hawthorn (weighted mean difference 7 W, 95% confidence interval [CI] 3-11 W), and in pressure-heart rate product (weighted mean difference -20, 95% CI -32 to -8). These findings remained when the analysis was limited to studies in which participants were known to have been taking other cardioactive medications. Improvements were also noted in exercise tolerance. A wide range of side effects was reported, the most common of which was vertigo (n = 8).
A later study not included by Pittler et al was published by Degenring and colleagues in 2003.7 They randomly assigned 143 patients with NYHA Class II CHF to an extract of two species of fresh hawthorn berries or placebo. The dose was reported as milligrams of OPC, but would standardize to between 200 mg and 650 mg of whole hawthorn extract per day. Treatment continued for approximately two months. The primary outcome was exercise tolerance, as determined by bicycle ergo-metry. Concomitant medications were not permitted beginning four weeks before enrollment in the study. At the end of the treatment period, there was a statistically significant difference in exercise tolerance in favor of the hawthorn group (mean -8.3, 95% CI -16.3 to -0.3). Similar proportions of hawthorn and placebo patients (13% hawthorn, 15% placebo) reported mild-to-moderate side effects, most of which were judged by study physicians as unlikely to be consequences of treatment.
Another report, for which full details were not immediately available in English, gave interim analysis results for the WISO cohort trial.8 A total of 952 patients with NYHA Class II CHF were enrolled, of whom 588 received hawthorn treatment. Treatment assignment was not random, and there were meaningful differences in the two groups with respect to age, sex, and concomitant medications. For the interim analysis, 130 matched pairs of patients were identified. At the time of the interim analysis, treatment had been ongoing for two years on average. Comparison of the hawthorn and non-hawthorn groups showed statistically significant improvements in fatigue, stress dyspnea, and palpitations, although definitions of these symptoms were not provided. The author also noted that hawthorn patients received fewer concomitant cardiac medications, but this may have been due to factors such as patient preference, which in turn would have influenced patients’ self-assignment to hawthorn or conventional therapy. A strength of these findings is that they represent "real-world" experience—not the carefully controlled conditions of most clinical trials.
A study included in the Pittler meta-analysis, but worth mentioning individually is that by Tauchert, published in 2002.9 This study randomized 209 patients with NYHA Class III CHF to 1,800 mg of WS 1442, 900 mg of WS 1442, or placebo. Patients with more or less severe CHF, those treated with digitalis in the previous six months, and those with serious cardiac or other comorbidities were excluded. Treatment continued for 16 weeks, after which maximal workload was assessed by bicycle ergometry. Findings included an increase in maximal workload in the 1,800 mg group as compared to the other two, and improvement in a scale score of typical heart failure symptoms in both hawthorn groups as compared to placebo. Patients in the placebo group reported adverse effects twice as often as those in either hawthorn group. While it is impressive to see results in Class III CHF similar to those shown in milder stages, this study’s findings should be viewed in light of the homogeneity of the study population and the funding of the study by a manufacturer of hawthorn extract.
Conclusion
Overall, the available evidence appears to suggest that there is some benefit to patients with mild CHF from the use of hawthorn extract. However, this evidence must be weighed against its limitations. Given the nature of CHF, it has proven difficult to conduct a study in patients with no major comorbidities and no significant concomitant medications. Given the lack of clarity as to hawthorn’s exact mechanism of action, it is not possible to say what other medications may confound, potentiate, or attenuate its apparent effect. It seems reasonable to assume that such effects would most likely be seen with coadministration of hawthorn and other cardioactive drugs. (It should be noted that at least one small study has found that coadministration of hawthorn and digoxin, with careful attention to dosing, appears to be safe.10) The concentration of studies in Germany also brings into question the reproducibility of their findings in other more diverse populations.
Finally, the wide range of dosages leaves open the question of how much is needed to achieve clinical
benefit. The studies reviewed by Pittler et al used doses ranging from
160 mg to 1,800 mg per day. There appears to be a trend toward higher
doses in more recently published studies, but the current evidence base
offers little guidance as to appropriate thresholds for efficacy and
safety.
| Table | |
| Types of yoga described in ancient Vedic texts3 | |
| Name | Emphasis |
| Bhakti yoga Jnana yoga Karma yoga Raja yoga Dhyana yoga Mantra yoga Hatha yoga |
Spirituality and devotion Wisdom Services without selfish motive Mastery of mind through focused concentration Meditation Repetition of sacred words Balancing of physical and mental energies |
Recommendation
No study published to date has shown significant harm from the use of hawthorn. Used carefully in a patient population that is likely to have fairly regular physician supervision, it should present no major risks and may offer therapeutic benefit. There is inadequate evidence as yet as to how it works, and many hypothesized mechanisms. Because of this, hawthorn should not be assumed to stand in for all of the potential agents that might be used together to manage CHF. Even if the use of hawthorn moderates some physical symptoms, it is most often still advisable to take other medications (such as antihypertensives) concomitantly. As has been emphasized before in this publication, it is critical for the treating clinician to have a clear picture of what the patient is taking, both prescription and over-the-counter agents. Given the focus on functional status in grading CHF, this physician-patient communication will help establish response to treatment and have the added benefit of making the patient’s concerns and preferences clear.
References
1. Chang Q, et al. Hawthorn. J Clin Pharmacol 2002;42:605-612.
2. Blumenthal M, et al. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000.
3. Pittler MH, et al. Hawthorn extract for treating chronic heart failure: Meta-analysis of randomized trials. Am J Med 2003;114:665-674.
4. Petkov E, et al. Inhibitory effect of some flavonoids and flavonoid mixtures on cyclic AMP phosphodiesterase activity of rat heart. Planta Medica 1981;43:183-186.
5. Chen ZY, et al. Endothelium-dependent relaxation induced by hawthorn extract in rat mesenteric artery. Life Sci 1998;63:1983-1991.
6. Veveris M, et al. Crataegus special extract WS 1442 improves cardiac function and reduces infarct size in a rat model of prolonged coronary ischemia and reperfusion. Life Sci 2004;74:1945-1955.
7. Degenring FH, et al. A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Cartaegisan) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine 2003;10:363-369.
8. Habs M.
Prospective, comparative cohort studies and their contribution to the
benefit assessments of therapeutic options: Heart failure treatment
with and without Hawthorn special extract WS 1442. Forsch
Komplementarmed Klass Naturheilkd 2004;11(Suppl 1):
36-39.
9. Tauchert M. Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J 2002;143:910-915.
10. Tankanow R, et al. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). J Clin Pharmacol 2003;43:637-642.
Sasser H. Use of hawthorn for mild congestive heart failure. Altern Med Alert 2005;8(8):89-92.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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