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Herbal Medicine for the Treatment of Cardiovascular Disease Clinical Considerations

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Herbal Medicine for the Treatment of Cardiovascular Disease Clinical Considerations REVIEW ARTICLE Herbal Medicine for the Treatment of Cardiovascular Disease Clinical Considerations Nick H. Mashour, MD; George I. Lin, MD; William H. Frishman, MD erbs have been used as medical treatments since the beginning of civilization and some derivatives (eg, aspirin, reserpine, and digitalis) have become mainstays of hu- man pharmacotherapy. For cardiovascular diseases, herbal treatments have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, ath- Herosclerosis, cerebral insufficiency, venous insufficiency, and arrhythmia. However, many herbal remedies used today have not undergone careful scientific assessment, and some have the poten- tial to cause serious toxic effects and major drug-to-drug interactions. With the high prevalence of herbal use in the United States today, clinicians must inquire about such health practices for car- diac disease and be informed about the potential for benefit and harm. Continuing research is nec- essary to elucidate the pharmacological activities of the many herbal remedies now being used to treat cardiovascular diseases. Arch Intern Med. 1998;158:2225-2234 Since the beginning of human civiliza- ceding year.2 This figure is probably tion, herbs have been an integral part of much higher for non–English-speaking society, valued for both their culinary and Americans. Despite this heavy use of medicinal properties. Herbal medicine has herbal medicines in the United States, made many contributions to commercial health practitioners often fail to ask drug preparations manufactured today in- about their use when taking clinical his- cluding ephedrine from Ephedra sinica tories. It is imperative that physicians (ma-huang), digitoxin from Digitalis pur- become more aware of the wide array of purea (foxglove), salicin (the source of as- herbal medicines available, as well as pirin) from Salix alba (willow bark), and learning more about their beneficial and reserpine from Rauwolfia serpentina adverse effects.3 (snakeroot), to name just a few. A natu- Part of the problem for both consum- rally occurring b-adrenergic blocking agent ers and physicians has been the paucity of with partial agonism has been identified scientific data on herbal medicines used in in an herbal remedy.1 The recent discov- the United States.4 As a result, those who ery of the antineoplastic drug paclitaxel wish to obtain factual information regard- from Taxus brevifolia (pacific yew tree) ing the therapeutic use or potential harm stresses the role of plants as a continuing of herbal remedies would have to obtain it resource for modern medicine. from books and pamphlets, most of which However, with the development of base their information on traditional repu- patent medicines in the early part of the tation rather than relying on existing sci- 20th century, herbal medicine has been entific research. One may wonder why the losing ground to new synthetic medi- herbal industry never chose to simply prove cines touted by scientists and physicians its products safe and effective. The answer to be more effective and reliable. Never- is primarily economical. With the slim theless, about 3% of English-speaking chance of patent protection for the many adults in the United States still report herbs that have been in use for centuries, having used herbal remedies in the pre- pharmaceutical companies have not pro- vided financial support for research on the 5 From the Department of Medicine, The Albert Einstein College of Medicine, Bronx, NY merits of herbal medicine. At the same (Dr Mashour); the Department of Family Medicine, Columbia Presbyterian Medical time, the National Institutes of Health have Center, New York, NY (Dr Lin); and the Departments of Medicine and Pharmacology, only been able to offer limited funding for New York Medical College/Westchester Medical Center, Valhalla, NY (Dr Frishman). this purpose. ARCH INTERN MED/ VOL 158, NOV 9, 1998 2225 ©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 This review examines herbal medicines that affect the cardiovas- Herbs for Cardiovascular Conditions With Severe Adverse Reactions cular system both in terms of effi- or Notable Drug Interactions* cacy and safety as gleaned from the scientific literature that is avail- Herbal Medicine Adverse Reaction/Drug Interaction Treatment able. These herbs are categorized un- Natural cardiac glycosides Ventricular tachyarrhythmia, bradycardia, Digoxin-specific (.20 plant sources) and heart block Fab antibody der the primary diseases they treat. Veratrum Bradycardia, A-V dissociation, hypotension, ECG changes responsive However, most herbal medicines (hellebore) and (rarely) seizures to atropine have multiple cardiovascular ef- Crataegus Potentiates digitalis activity NA fects that frequently overlap. The (hawthorn) purpose of this organization is to Salvia miltiorrhiza Potentiates warfarin activity NA simplify, not to pigeonhole herbs un- (dan-shen) Aesculus hippocastanum Renal and hepatic toxic effects Dialysis to reduce der specific diseases. In general, the (horse chestnut) toxic levels dilution of active components in herbal medicines results in fewer ad- *A-V indicates arteriovenous anastomosis; ECG, electrocardiographic; and NA, data not applicable. verse and toxic effects in compari- son with the concentration of ac- mango), Cheiranthus cheiri (wall- ander intoxication, as well as other tive components in the allopathic flower), Convallaria majalis (lily of natural glycosides, is virtually iden- medicines. However, these adverse the valley, convallaria), Cryptoste- tical to digoxin overdose. Morbid- effects and drug interactions should gia grandiflora (rubber vine), Hel- ity and mortality are mainly related not be overlooked; cardiovascular leborus niger (black hellebore), Hel- to cardiotoxic adverse effects that disease is a serious health hazard and leborus viridus, Nerium oleander usually include life-threatening ven- no herbal remedy regimen should be (oleander), Plumeria rubra (frangi- tricular tachyarrhythmias, brady- initiated without careful consider- pani), Selenicerus grandiflorus (cac- cardia, and heart block. The diag- ation of its potential impact (Table). tus grandiflorus), Strophanthus his- nosis should rely on the clinical pidus and Strophanthus kombe presentation of unexplained hyper- CONGESTIVE HEART FAILURE (strophanus), Thevetia peruviana kalemia, and cardiac, neurologic, (yellow oleander), and Urginea mar- and gastrointestinal symptoms.19 A number of herbs contain potent itima (squill).5,7-15 Even the venom The diagnosis can be further cardioactive glycosides, which have glands of the animal Bufo marinus supported by the detection of the positive inotropic actions on the (cane toad) contain cardiac glyco- substance digoxin in a radioimmu- heart. The drugs digitoxin, derived sides.8 Recently, the digitalislike ste- noassay for digoxin. However, the from either D purpurea (foxglove) or roid in the venom of the B marinus extent of cross-reactivity between the Digitalis lanata, and digoxin, de- toad was identified as a previously cardiac glycosides from herbal rived from D lanata alone, have been described steroid, marinobufa- sources and antibodies used in the used in the treatment of congestive genin. Marinobufagenin demon- radioimmunoassays has not been heart failure for many decades. Car- strated high digoxinlike immuno- clearly defined.26 For this reason, di- diac glycosides have a low therapeu- reactivity and was antagonized with goxin assays may serve to confirm tic index, and the dose must be ad- an antidigoxin antibody.16 the suspected diagnosis but not to justed to the needs of each patient. Accidental poisonings and even quantify the severity. Once the di- The only way to control dosage is to suicide attempts with ingestion of agnosis has been established, the use use standardized powdered digi- cardiac glycosides are abundant in of digoxin-specific Fab antibody talis, digitoxin, or digoxin. When the medical literature.17-21 Some fragments may be helpful in the 12 different strains of D lanata herbal remedies (eg, Siberian gin- treatment of severe intoxication. plants were cultured and exam- seng) can elevate synthetic digoxin Other modalities, such as dialysis, ined, their total cardenolide yield drug levels and cause toxic ef- cannot be easily facilitated be- ranged from 30 to almost 1000 fects.22 In the United States, there are cause, like digoxin, natural glyco- nmol/1 g.6 As is evident, treating about 15 000 intoxications due to ac- sides are distributed extensively into congestive heart failure with non- cidental or intentional ingestion of peripheral tissues. standardized herbal drugs would be poisonous plants annually.23 In 1993, dangerous and foolhardy. 2388 toxic exposures in the United HYPERTENSION Some common plant sources of States were reported to be due to cardiac glycosides include D pur- plant glycosides. Of these, the larg- The root of R serpentina (snake- purea (foxglove, already men- est percentage were attributed to ole- root), the natural source of the alka- tioned), Adonis microcarpa and Ado- ander (ie, 25%).24 In the case of ole- loid reserpine, has been a Hindu nis vernalis (adonis), Apocynum ander, all plant tissues, including the Ayurvedic remedy since ancient cannabinum (black Indian hemp), seeds, roots, stems, leaves, berries, times. In 1931, Indian literature first Asclepiascurassavica (redheaded cot- and blossoms, are considered ex- described the use of R serpentina
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