Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study.
OBJECTIVE
Tegaserod, a partial 5-HT(4) agonist previously approved for treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation, was suspended from US marketing in 2007, based on pooled clinical trial results which contained a signal suggesting increased risk of cardiovascular ischemic events (CVIEs). We sought to evaluate whether there was an association between tegaserod and CVIE in a setting of routine clinical practice.


METHODS
This was a matched cohort study conducted within a large US health insurance database, involving 52 229 patients who initiated tegaserod and 52 229 patients with similar characteristics who did not initiate tegaserod. Participants were followed for up to 6 months for the occurrence of CVIE (myocardial infarction, acute coronary syndrome, coronary revascularization, and stroke). Outcomes were identified using insurance claims and were confirmed by review of medical records. We conducted as-matched analyses providing hazard ratios (HRs) along with 95% confidence intervals (95% CI) and as-treated analyses accounting for changes in dispensed therapy.


RESULTS
There was no increased risk of CVIE associated with tegaserod treatment. The as-matched association between tegaserod and ischemic cardiovascular outcomes (HR = 0.95, 95% CI 0.73-1.23) and stroke (HR = 0.90, 95% CI 0.46-1.77) did not change substantially in the as-treated analyses (cardiovascular relative risk [RR] = 1.14, 95% CI 0.83-1.56; stroke: RR = 1.09, 95% CI = 0.49-2.02). The results were largely unaffected by adjustment for characteristics or subgroup analyses.


CONCLUSIONS
In this observational study of tegaserod use, we found no evidence for an increased risk of CVIE in tegaserod users.
Loughlin
Jeanne
J
Ingenix, i3 Drug Safety, Waltham, MA, USA.
Quinn
Sherry
S
Rivero
Elena
E
Wong
Judy
J
Huang
Jiaquing
J
Kralstein
Jeffrey
J
Earnest
David L
DL
Seeger
John D
JD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007223:Infant; D007345:Insurance Claim Review; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000453:epidemiology; D012737:Sex Factors; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D055815:Young Adult
D005765:Gastrointestinal Agents; D007211:Indoles; C105050:tegaserod