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Associate Dean, College of Science; Director, Walther Cancer Research Center, University of Notre Dame, Notre Dame, IN
Professor, Division of Pharmacotherapy, The University of Texas at Austin and the Health Science Center in San Antonio, San Antonio, TX
Reprints: Rudolph M Navari MD PhD, College of Science, 250 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556-5670, FAX 574/631-4939, navari.1{at}nd.edu
OBJECTIVE: To review the electrocardiographic (ECG) and cardiovascular effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists preclinically, in healthy volunteers, and in patients undergoing chemotherapy or surgery.
DATA SOURCES: A MEDLINE search was performed of clinical trials and preclinical data published between 1963 and December 2002 assessing the ECG and cardiovascular effects of 5-HT3 receptor antagonists, supplemented with reviews and secondary sources.
STUDY SELECTION AND DATA EXTRACTION: All of the articles identified were evaluated and all information deemed relevant was included in this review.
DATA SYNTHESIS: There are no clinically relevant differences in efficacy and safety among the available 5-HT3 receptor antagonists for prevention and treatment of chemotherapy-induced and postoperative nausea and vomiting. As a class, they have well-defined electrophysiologic activity. Changes in ECG parameters (PR, QRS, QT, QTc, JT intervals) are small, reversible, clinically insignificant, and independent of the patient population studied, and patients are asymptomatic during these changes. ECG changes are most prominent 1ñ2 hours after a dose of dolasetron, ondansetron, and granisetron and return to baseline within 24 hours. Clinically important adverse cardiovascular events associated with these changes are rare. No serious cardiac events (including torsade de pointes) arising from ECG interval changes have been attributed to 5-HT3 receptor antagonist use.
CONCLUSIONS: Clinical data demonstrate that ECG interval changes are a class effect of the 5-HT3 receptor antagonists. Theoretical concern regarding cardiovascular adverse events with these agents is not supported by clinical experience. The significant benefits of these agents outweigh the theoretical small risk of meaningful cardiovascular events.
Key Words: dolasetron, electrocardiogram, granisetron, 5-HT3 receptor antagonist, ondansetron
Published Online, July 10, 2003. www.theannals.com, DOI 10.1345/aph.1C510
THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE
UNIVERSAL PROGRAM NUMBER: 407-000-03-026-H01
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A. J Coop Comment: electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine-3 receptor antagonists Ann. Pharmacother., December 1, 2003; 37(12): 1918 - 1918. [Full Text] [PDF]
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R. M Navari and J. M Koeller Authors' Reply Ann. Pharmacother., December 1, 2003; 37(12): 1918 - 1919. [Full Text] [PDF]
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