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Drug Safety

, Volume 29, Issue 6, pp 523–535 | Cite as

Adverse-Event Profile of Crataegus Spp.

A Systematic Review
  • Claudia Daniele
  • Gabriela Mazzanti
  • Max H. Pittler
  • Edzard Ernst
Review Article

Abstract

Crataegus spp. (hawthorn) monopreparations are predominantly used for treating congestive heart failure. The effectiveness of hawthorn preparations (flowers with leaves; berries) is documented in a number of clinical studies, reviews and meta-analyses. The aim of this article is to assess the safety data of all available human studies on hawthorn monopreparations.

Systematic searches were conducted on MEDLINE, EMBASE, AMED, The Cochrane Library, the UK National Research Register and the US ClinicalTrials.gov (up to January 2005). Data were requested from the spontaneous reporting scheme of the WHO. Hand searches were also conducted in a sample of relevant medical journals, conference proceedings, reference lists of identified articles and our own files. Eight manufacturers of hawthorn-containing preparations were contacted and asked to supply any information on adverse events or drug interactions. Data from all clinical studies and reports were assessed. Only human studies on monopreparations were included. Data from hawthorn-containing combination preparations and homeopathic preparations were excluded. All studies were read and evaluated by one reviewer and independently verified by at least one additional reviewer.

Twenty-nine clinical studies were identified, of which 24 met our inclusion criteria. A total of 7311 patients were enrolled, and data from 5577 patients were available for analysis. The daily dose and duration of treatment with hawthorn monopreparations ranged from 160 to 1800mg and from 3 to 24 weeks, respectively. The extracts most used in the clinical trials were WS 1442 (extract of hawthorn standardised to 18.75% oligomeric procyanidins) and LI 132 (extract of hawthorn standardised to 2.25% flavonoids). Overall, 166 adverse events were reported. Most of these adverse events were, in general, mild to moderate; eight severe adverse events have been reported with the LI 132 extract. The most frequent adverse events were dizziness/vertigo (n = 15), gastrointestinal complaints (n = 24), headache (n = 9), migraine (n = 8) and palpitation (n = 11). The WHO spontaneous reporting scheme received 18 case reports. In the identified trials, the most frequent adverse events were dizziness (n = 6), nausea (n = 5), fall (n = 2), gastrointestinal haemorrhage (n = 2), circulation failure (n = 2) and erythematous rash (n = 2). There were no reports of drug interactions.

In conclusion, all data reviewed in this article seem to indicate that hawthorn is well tolerated even if some severe adverse events were reported; this suggests that further studies are needed to better assess the safety of hawthorn-containing preparations. Moreover, the unsupervised use of this drug can be associated with problems, especially if given with concomitant medications.

Keywords

Chronic Heart Failure Randomise Clinical Trial Frequent Adverse Event International Drug Monitoring Oligomeric Proanthocyanidins 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors wish to thank Dr Antonella Di Sotto, Department of Pharmacology of Natural Substance and General Physiology, University of Rome, ‘La Sapienza’, Rome, Italy, for her support.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Chang Q, Zuo Z, Harrison F, et al. Hawthorn. J Clin Pharmacol 2002; 42: 605–12605-12PubMedCrossRefGoogle Scholar
  2. 2.
    Cupp MJ. Hawthorn. In: Cupp MJ, Annonn J. Toxicology and clinical pharmacology of herbal products. Totowa (NJ): Humana Press, 2000: 253–8CrossRefGoogle Scholar
  3. 3.
    Williamson EM. British herbal pharmacopoeia, 1983. Bournemouth: British Herbal Medicine Association (BHMA) Publications, 2003Google Scholar
  4. 4.
    Weiss RF, Fintelmann V. Herbal medicine. New York: Thieme Stuttgart, 2000Google Scholar
  5. 5.
    Newall A, Anderson LA, Phillipson JD. Herbal medicines: a guide for health-care professionals. London: The Pharmaceutical Press, 1996Google Scholar
  6. 6.
    Blumenthal M. The ABC clinical guide to herbs. Austin (TX): American Botanical Council, 2003Google Scholar
  7. 7.
    Blumenthal M, Busse WR, Goldberg A. The complete Commission E monographs. Austin (TX): American Botanical Council, 2000Google Scholar
  8. 8.
    Schussler M, Holz J, Fricke U. Myocardial effects of flavonoids from Crataegus species. Arzneimittel Forschung 1995; 45: 842–5PubMedGoogle Scholar
  9. 9.
    Weiss RF, Fintelmann V. Herbal medicine. New York: Thieme Stuttgart, 2000Google Scholar
  10. 10.
    Rigelsky JM, Sweet BV. Hawthorn: pharmacology and therapeutic uses. Am J Health Syst Pharm 2002; 59: 417–22PubMedGoogle Scholar
  11. 11.
    Societàl Italiana di Fitoterapia, Organizzazione Mondiale della Sanità (OMS). Monografie di piante medicinali. Vol. 2. Abbiategrasso (Milan), Italy: Le Nuove Scritture, 2004Google Scholar
  12. 12.
    Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med 2003; 114: 665–74PubMedCrossRefGoogle Scholar
  13. 13.
    Reynolds JEJ, editor. Hawthorne. Martindale: the extra pharmacopoeia. London: The Royal Pharmaceutical Society of Great Britain, Pharmaceutical Press, 1996: 1600Google Scholar
  14. 14.
    Iwamoto M, Ishizaki T, Sato T. Klinische Wirkung von Crataegutt® bei Herzerkrankungen ischa mischer und/oder hypertensiver Genese: Eine multizentrische Doppelblindstudie. Planta Med 1981; 42: 1–16PubMedCrossRefGoogle Scholar
  15. 15.
    O’Connolly M, Bernhoft G, Bartsch G. Behandlung alterer, multimorbider Patienten mit stenokardischen Beschwerden: Eine placebokontrollierte crossover-Doppelblindstudie mit Crataegutt® novo. Therapiewoche 1987; 37: 3587–600Google Scholar
  16. 16.
    O’Connolly M, Jansen W, Bernhôft G, et al. Treatment of decreasing cardiac performance (NYHA stages I to II) in advanced age with standardized crataegus extract. Fortschr Med 1986; 42: 805–8Google Scholar
  17. 17.
    Hanak T, Brûckel MH. Behandlung von leichten stabilen Formen der Angina pectoris mit Crataegutt novo. Therapiewoche 1983; 33: 4331–3Google Scholar
  18. 18.
    Weikl A, Assmus KD, Neukum-Schmidt A. Objective confirmation of the efficacy of a special crataegus extract WS1442 in patients with cardiac insufficiency (NYHA II). Fortschr Med 1996; 114: 291–6PubMedGoogle Scholar
  19. 19.
    Eichstâdt H, Stôrk T, Môckel M. Wirksamkeit und Vertrâglichkeit von Crataegus-Extrakt WS®1442 bei herzinsuffizienten Patienten mit eingeschrankter linksventrikulârer Funktion. Perfusion 2001; 14: 212–7Google Scholar
  20. 20.
    Leuchtgens H. The crataegus special extract WS 1442 in patients with cardiac insufficiency NYHA II: a placebo-controlled double-blind study. Fortschr Med 1993; 111: 352–4PubMedGoogle Scholar
  21. 21.
    Zapfe G. Clinical efficacy of crataegus extract WS®1442 in congestive heart failure NYHA class II. Phytomedicine 2001; 8: 262–6CrossRefGoogle Scholar
  22. 22.
    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: 910–5PubMedCrossRefGoogle Scholar
  23. 23.
    Staiger J, Kuhn H, Spâth J. Zur kardialen Wirksamkeit von low-dose digitoxin (0.07 mg) and crataegus. Med Welt 1987; 38: 1023–8Google Scholar
  24. 24.
    Eichstâdt H, Bâder M, Danne O. Crataegus-Extrakt hilft dem Patienten mit NYHA II-Herzinsuffizienz. Therapiewoche 1989; 39: 3288–96Google Scholar
  25. 25.
    Weikl A, Noh HS. Der Einfluss von Crataegus bei globaler Herzinsuffizienz. Herz Gefâsse 1992; 12: 6–24Google Scholar
  26. 26.
    Tauchert M, Gildor A, Lipinski J. High-dose crataegus (hawthorn) extract WS®1442 in the treatment of NYHA stage II heart failure. Herz 1999; 24: 465–74PubMedCrossRefGoogle Scholar
  27. 27.
    Habs M. Prospective, comparative cohort studies and their contribution to the benefit assessment of therapeutic options: heart failure treatment with and without hawthorn special extract WS 1442. Forsch Komplementârmed Klass Naturheilkd 2004; 11: S36–9CrossRefGoogle Scholar
  28. 28.
    Alexander A. Klinische Wirkung des Crataegus Extraktes LI132 bei der Therapie der Herzinsuffizienz im Stadium II der New York Heart Association. Eine randomisierte, plazebokontrollierte Doppelblindstudie an N = 73 Patienten [doctoral thesis; online]. Available from URL: http://edoc.hu-berlin.de/docviews/abstract.php?lang=ger&id=10095 [Accessed 2006 Jan 27]Google Scholar
  29. 29.
    Bôadigheimer K, Chasa D. Effectiveness of hawthorn extract at a dosage of 3 × 100mg per day: multicentre double-blind trial with 85 NYHA stage II heart failure patients. Mûanch Med Wochenschr 1994; 136: S7–S11Google Scholar
  30. 30.
    Schmidt U, Kuhn U, Ploch M, et al. Efficacy of hawthorn (crataegus) preparation LI132 in 78 patients with chronic congestive heart failure defined as NYHA functional class II. Phytomedicine 1994; 1: 17–24CrossRefGoogle Scholar
  31. 31.
    Tauchert M, Ploch M, Hubner WD. Effectiveness of the hawthorn extract LI 132 compared with the ACE inhibitor captopril. Mûanch Med Wochenschr 1994; 136: S27–33Google Scholar
  32. 32.
    Fischer K, Jung F, Koscielny J, et al. Crataegus-extract vs methyldidoxin. Mûanch Med Wochenschr 1994; 136: S35–8Google Scholar
  33. 33.
    Fôrster A, Fôrster K, Bûhring M, et al. Crataegus bei mâβiger reduzierter linksventrikulârer Auswurffraktion. Mûanch Med Wochenschr 1994; 136: S21–6Google Scholar
  34. 34.
    Schmidt U, Albrecht M, Podzuweit H. High dosed therapy with crataegus extract in patients suffering from heart failure NYHA stage I and II. Z Phytother 1998; 19: 22–30Google Scholar
  35. 35.
    Rietbrock N, Hamel M, Hempel B. Efficacy of a standardized extract of fresh crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure (NYHA II). Arzneimittel Forschung 2001; 51: 793–8PubMedGoogle Scholar
  36. 36.
    Degenring FH, Suter A, Weber M, et al. A randomised double blind placebo controlled clinical trial of a standardised extract of fresh crataegus berries (Crataegisan®) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine 2003; 10: 363–9PubMedCrossRefGoogle Scholar
  37. 37.
    Walker AF, Marakis G, Morris AP, et al. Promising hypotensive effect of hawthorn extract: a randomised double-blind pilot study of mild, essential hypertension. Phytother Res 2002; 16: 48–54PubMedCrossRefGoogle Scholar
  38. 38.
    Barnes J, Mills SY, Abbot NC. Different standards of reporting of ADRs to herbal remedies and conventional OTC medicines: face to face interviews with 515 users of herbal remedies. Br J Clin Pharmacol 1998; 45: 496–500PubMedCrossRefGoogle Scholar
  39. 39.
    Ernst E, Pittler MH, Stevinson C, et al. The desktop guide to complementary and alternative medicine: an evidence based approach. Edinburgh: Mosby, 2001Google Scholar
  40. 40.
    Tankanow R, Tamer HR, Streetman DS, et al. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). Clin Pharmacol 2003; 43: 637–42Google Scholar
  41. 41.
    Mills S, Bone K. The essential guide to herbal safety. Edinburgh: Elsevier Churchill Livingstone, 2005Google Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Claudia Daniele
    • 1
  • Gabriela Mazzanti
    • 1
  • Max H. Pittler
    • 2
  • Edzard Ernst
    • 2
  1. 1.Department of Human Physiology and Pharmacology of Natural Substance and General PhysiologyUniversity of Rome ‘La Sapienza’RomeItaly
  2. 2.Peninsula Medical School, Complementary Medicine, Universities of Exeter and PlymouthExeterUK

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