ALTERNATIVE MEDICINES FOR CARDIOVASCULAR DISEASES
The incredible surge in use of alternative medicines must be accompanied by increasing numbers of well-controlled basic science and clinical trials conducted to develop an understanding of the safety and efficacy of such medications. Recent estimates1,2 suggest a US national expenditure of $5 to $20 billion for herbal supplements. In a national survey2 of alternative medicine use in the United States from 1990 to 1997, increases in patient visits to alternative medicine practitioners exceeded visits to primary care practitioners. It has been estimated that millions of adults take combinations of prescription and herbal medications routinely. A standard of care for alternative medicine must be developed, and all health care practitioners must be educated to support this increasingly popular trend that is likely to be a future "mainstay" of therapy.
When reading the literature on this topic, what immediately comes to mind is the circular nature of life and that the folklore and traditions of ancient civilizations have become mainstream. Many current pharmaceuticals have their origin in plants, trees, and roots. For instance, William Withering's 1785 monograph on the therapeutic effect of the leaves of the foxglove plant, Digitalis purpura, contains compelling evidence for the use of digoxin in the treatment of congestive heart failure.3 The belladonna drug atropine, an anticholinergic used as a chronotropic agent, is an alkaloid derived from the Solanaceae plant, Atropa belladonna, or Datura stramonium, also known as Jamestown or jimsomweed, stinkweed, thorn-apple, and devil's apple.4 The terms phytomedicine or phytotherapeutics denote the study of plant-derived products, and this branch of study is very active, even in our world of high-technology medicine.1
Because many of the herbal therapies available today are described as "natural," the average person is unable to distinguish the potentially harmful nature of individual agents. In the United States, the Food and Drug Administration (FDA) classifies herbal agents as nutritional supplements through the Dietary Supplement Health and Education Act (DSHEA) of 1994.5 The FDA does not regulate the quality or quantity of ingredients and provides a disclaimer that such products are not intended to diagnose, treat, cure, or prevent disease.6 This current lack of scrutiny is difficult to comprehend when the FDA imposes such strict regulation of the traditional pharmaceutical market, and, even with this level of examination, an occasional drug such as terfenadine and cisapride becomes available to the public with significant adverse effects. In 1992 a congressional mandate established a site now known as the National Center for Complementary and Alternative Medicine (NCCAM)1 to increase patient awareness of these medicines, due in part to the rapid increase in the use of herbal products beginning in the 1990s. Currently, this center serves as a source of reliable information to the consumer.
Any type of medication, from traditional to herbal categories, must target a condition or disease process and have benefit to the patient with a minimum of side effects. For traditional medications, laboratory studies and preclinical evaluation precede four phases of clinical trials, resulting in a time line of 10 to 20 years for many of these investigational drugs. The rigorous clinical trials are defined as follows: phase 1 is conducted in normal volunteers or a target population of severely ill patients to establish dosage information. Phase 2 trials evaluate efficacy and safety in a small population of patients with the disease or condition to be treated, and phase 3 trials continue to gather efficacy and safety data in large numbers of patients in controlled studies. Following FDA approval and market availability, phase 4 trials are conducted to continue safety and efficacy profiles and to gather further information on treatment and adverse events.
It would be a challenge to apply the same criteria for development and experimentation to herbal medications. However, a fundamental problem that must be overcome is the lack of a standardized extract of many herbal medications.7 Then, controlled, randomized, double-blind, and placebo trials, which parallel the four phases of clinical trials for traditional medications, should be conducted. This approach would provide scientific evidence as a foundation for the use of herbal medications in target diseases. Such an approach is imperative, as herbal medications can no longer be ignored as an option to treatment. Studies have shown adverse effects of herbs to include hypersensitivity reactions, anemia, and hepatic and renal failure from commonly available herbal preparations,8 underscoring the importance of scientific inquiry and formal data collection and analysis.
The growing popularity of herbal medicines, and the lack of standardization in this field, obligates the nurse to develop an awareness and understanding of the current use of herbal medicines. Current, cutting-edge clinical practice must include a critical analysis of safety and efficacy data obtained from scientific experimentation, the development of standard protocols for clinical use, development of patient educational materials for communication with patients, and formal documentation of adverse effects. Herbal medications, although centuries old, have entered a new era of scientific research and discovery. Nurses are challenged to bridge old and new, conventional and alternative therapies in the management of patients.
This issue of The Journal of Cardiovascular Nursing (16:4) addresses the use of herbals, such as hawthorn, coenzyme Q10, Ginkgo biloba, garlic, and soy for cardiovascular diseases and describes various herb-drug interactions that may influence standard therapy. The first phytomedicine discussed is hawthorn (Crataegus monogyna), which has been approved for use in Germany for congestive heart failure. Fong and Bauman review the data demonstrating that hawthorn may be a useful adjunctive agent in the treatment of left ventricular dysfunction. The mechanism of action of hawthorn is blockade of Na+-K+ ATPase, possible inhibition of phosphodiesterase III, vasodilatory action in the coronary circulation and peripheral vasculature through angiotensin-converting enzyme (ACE) inhibition, and perhaps beta blockade. These activities mimic the traditional pharmaceutical effects of digoxin, ACE inhibitors, and beta blockers. Small controlled studies have shown consistently that hawthorn improves exercise tolerance and dyspnea and fatigue in patients with mild to moderate heart failure. There is evidence suggesting an increase in ejection fraction. There are few adverse effects related to hawthorn, but a defining study to establish the efficacy of hawthorn for treatment of congestive heart failure (CHF) is critical. The ongoing SPICE study (Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in CHF) should provide this level of information to providers to determine absolute patient benefit.
A different approach for the treatment of congestive heart failure targets coenzyme Q10 deficiency. Sarter suggests that administration of coenzyme Q10 may improve myocardial metabolic function. New York Heart Association (NYHA) functional class II or III patients who received coenzyme Q10 showed improvement in cyanosis, edema, and dyspnea, among other symptoms. However, in a different study of NYHA class III or IV patients, outcome measures of ejection fraction, peak oxygen consumption, and exercise duration were unchanged and no different in groups receiving either coenzyme Q10 or placebo. Coenzyme Q10 may have more efficacy in the treatment of ischemic heart disease and hypertension. There appear to be myocardial protective benefits following acute myocardial infarction. In hypertensive patients, concomitant use of coenzyme Q10 and antihypertensives have resulted in reduced doses of antihypertensives.
Antioxidant activity is thought to inhibit free radical-mediated myocardial damage in the injured myocardium during ischemia. As described by Mahady, Ginkgo biloba, a deciduous tree with large fan-shaped leaves from which the herb is derived, has free-radical scavenging activity that may make it useful for the prevention and treatment of acute myocardial infarction. Ginkgo biloba also decreases platelet aggregation and causes vasorelaxation by blockade of nitric oxide metabolism, which may improve circulation in the systemic circulation and cerebral blood vessels. Although few adverse effects are associated with Ginkgo biloba, ginkgo's antiplatelet effect is significantly enhanced when used in combination with ticlopidine, with results of one study showing combined treatment prolonged bleeding times by 150%. Self-medication is not recommended.
The reputed health-promoting benefits of garlic (Allium sativum L) are described in the review by Brace. Garlic may inhibit platelet aggregation and enhance fibrinolytic potential, but the evidence to date does not support other therapeutic claims. Research has not supported garlic as an effective antihypertensive. Garlic may cause minor reductions in total cholesterol, low-density lipoprotein (LDL), and triglyceride levels or augment improvements from the combination of other treatments (ie, low-cholesterol diet or fish oil consumption). Garlic has not demonstrated consistent lowering of blood lipids when used alone and in doses where compliance can be expected.
A reduction in blood lipids is critical to improving outcome in patients with cardiovascular disease. Hasler describes the health effects of soy, which reduces total cholesterol by 10% and can decrease the risk of coronary heart disease by 20%. The evidence supporting the effectiveness of soy is so compelling that the FDA now will allow certain soy products to make this health claim on their packaging. The main source of soy is soybeans, but soluble fiber from whole-oat products or psyllium seed husk also contain significant quantities of soy. Soy protein is comparable to animal protein, but Western diets continue to include small quantities of soy as part of the total daily protein. In addition to the lipid-lowering capability of soy, inhibition of LDL oxidation to decrease atherosclerotic plaque formation and the accompanying improvement in arterial compliance may contribute to the reduction in cardiovascular risk.
Rarely do patients take only one medication or one herbal agent. Nurses must recognize that herb-drug interactions may produce untoward effects. Interactions may impact bioavailability or drug metabolism, cause synergistic or inhibitory activity, or result in an increase in adverse effects. The review by Awang and Fugh-Berman focuses on the interaction of commonly used cardiac drugs and herbal agents. Cardiac glycoside-containing compounds, Siberian ginseng (Eleutherococcus senticosus) and the Chinese silk vine (Periploca sepium), have been shown to falsely indicate an elevated digoxin level when no symptoms of digitalis toxicity are noted. An interaction between St John's wort and digoxin may prove more hazardous because it has been associated with a 25% reduction of digoxin serum level. Ephedra or ma huang (Ephedra sinica) produces significant hypertension when co-administered with monoamine oxidase (MAO) inhibitors and should be avoided. Additive anticoagulant activity has been reported when Ginkgo biloba and garlic are concurrently administered with warfarin. The prevalence of such interactions has been exaggerated, but, when they occur, herb-drug interactions can cause problems in sensitive patients and those taking drugs with a narrow therapeutic window.
All authors in this issue stress that many of the reported results cannot be generalized because studies lacked appropriate controls, were conducted on small samples, and involved non-standard herbal plant extracts. The Outcomes Department article by Deaton and Weintraub notes that another important issue is the time period during which the trials were conducted. Many evaluate a certain therapy against standard care, but standard care is a moving target. The implication for the clinician, whether counseling patients on the use of herbal therapy or inquiring about an individual's use of these agents, is the need to develop a strong foundation of knowledge from sources with scientific merit and to add to this growing body of knowledge and fact.9 Admittedly, we recognize that this knowledge must be added to that addressing the already large numbers of traditional pharmaceuticals that nurses must know, recognize, and understand. The following strategies are advocated as a beginning template for care of patients:
* Use a standard, nonthreatening line of questions on herbal drug therapy to include vitamins and dietary supplements during history and physical examination.
* Provide sources of pharmacologic information (textbooks, pamphlets, research articles) in hospitals, clinics, and offices.
* Continue pursuing education in herbal therapy.
* Become an advocate for regulation at a federal level to require basic levels of standardization.
* Educate patients on the safe use of herbal therapy to maximize efficacy and minimize adverse effects.
* Develop controlled research protocols to implement clinical trials with scientific rigor.
The most critical message to be delivered to patients is that herbal therapy should not be considered a substitute for standard health care, and that these medications should not be used in lieu of conventional pharmaceuticals. Whether patients are using these agents to treat a chronic condition or as preventive health care, they must be made aware that these are drugs with pharmacodynamic effects on the body and that judicious use is imperative; they are not mere "alternative" substances without potential consequence. The alternative to this may prove fatal.
-Michele E. Gold, PhD, CRNA
Associate Professor of Clinical Nursing
Department of Nursing
University of Southern California
Los Angeles, California
-Norman Farnsworth, PhD
Research Professor of Pharmacognosy
College of Pharmacy
University of Illinois at Chicago
Chicago, Illinois
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