title: Lack of association of tegaserod with adverse cardiovascular outcomes in a matched case-control study.
abstract: Tegaserod is a first-in class selective serotonin 4 receptor agonist approved for the treatment of irritable bowel syndrome. In March 2007, the US Food and Drug Administration (FDA) suspended its use citing increased cardiovascular (CV) events in clinical trials. However, there is no known mechanistic basis for an adverse CV effect. To reassess the CV safety of tegaserod, teagaserod-treated patients (pts) in the Intermountain Healthcare database were identified (n = 2603), matched 1:6 with untreated (n = 15,618) patients by age, sex, and date of tegaserod initiation, and followed for an average of 2.5 years. Age averaged 38.6 +/- 13.5 years, and 94% were female. Cardiovascular event rates were low and similar in patients treated with tegaserod and matched untreated patients. For the primary composite CV endpoint, 54 (0.35%) untreated and 12 (0.46%) treated pts had an event (treated OR = 1.27, 95% CI: 0.68-2.38, P =.46), with 7 and 0 events, respectively, occurring within 3 months. A total of 12 (0.1%) untreated and 1 (<0.1%) treated pts were hospitalized for a myocardial infarction (MI). 36 (0.2%) untreated and 10 (0.4%) treated pts for a cardiovascular accident, and 1 pt in each group for unstable angina. A total of 6 (<0.1%) untreated and no treated pts died from cardiac causes. Event rates were comparable to expected rates in this population of mostly premenopausal women. This large epidemiologic study failed to confirm a reported large event differential for tegaserod that was noted incidentally in a clinical trials database, suggesting that the prior observation may have been due to chance.
authors: Cardiovascular Department, Intermountain Medical Center, Murray, Utah 84107, USA. jeffrey.anderson@imail.org
authors: Jeffrey L
authors: JL
authors: Anderson
authors: Heidi T
authors: HT
authors: May
authors: Tami L
authors: TL
authors: Bair
authors: Joseph B
authors: JB
authors: Muhlestein
authors: Benjamin D
authors: BD
authors: Horne
authors: John F
authors: JF
authors: Carlquist
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D016022:Case-Control Studies; D019992:Databases as Topic; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D005765:Gastrointestinal Agents; D007211:Indoles; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists; C105050:tegaserod