Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists.
OBJECTIVE
To review the electrocardiographic (ECG) and cardiovascular effects of 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonists preclinically, in healthy volunteers, and in patients undergoing chemotherapy or surgery.


METHODS
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-HT(3) receptor antagonists, supplemented with reviews and secondary sources.


METHODS
All of the articles identified were evaluated and all information deemed relevant was included in this review.


RESULTS
There are no clinically relevant differences in efficacy and safety among the available 5-HT(3) 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 1-2 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-HT(3) receptor antagonist use.


CONCLUSIONS
Clinical data demonstrate that ECG interval changes are a class effect of the 5-HT(3) 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.
Navari
Rudolph M
RM
College of Science and Walther Cancer Research Center, University of Notre Dame, Notre Dame, IN 46556-5670, USA. navari.1@nd.edu
Koeller
Jim M
JM
D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D017829:Granisetron / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D017294:Ondansetron / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011807:Quinolizines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013514:Surgical Procedures, Operative / Q000009:adverse effects
D000932:Antiemetics; D017829:Granisetron; D007211:Indoles; D017294:Ondansetron; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron