Re-evaluation of the Cardiovascular Safety Profile of Tegaserod: A Review of the Clinical Data

Abstract

Tegaserod is a 5-HT4 receptor agonist approved for irritable bowel syndrome with constipation in women <65 years of age without a history of cardiovascular ischemic events. Safety data are presented from 2 external adjudications from the 2018 Gastrointestinal Drugs Advisory Committee meeting supporting tegaserod's reintroduction after its voluntary 2007 withdrawal. Withdrawal was based on an internal adjudication using pooled placebo-controlled tegaserod data to identify potential cardiovascular ischemic signals. An independent committee conducted an external adjudication to evaluate 24 possible cardiovascular ischemic events (tegaserod: n= 20; placebo: n= 4) identified internally. A second independent external adjudication further evaluated these events. A total of 18,645 patients were included (tegaserod: n= 11,614; placebo: n= 7031). The first adjudication identified 14 (0.075%) events (tegaserod: n= 13 [0.11%]; placebo: n= 1 [0.014%]). All patients had ≥1 cardiovascular risk factor, and 11 had ≥2. The second adjudication identified 390 events, 24 (0.13%) were classified as probable new or worsening events (tegaserod: 18 [0.16%]; placebo: 6 [0.09%]). For tegaserod, 7 (0.06%) were coronary or cerebrovascular ischemic events compared with 1 (0.01%) for placebo (odds ratio, 4.24; 95% confidence interval, 0.52-34.74; P= .273). All tegaserod patients reporting cardiovascular events had ≥1 risk, including cardiovascular disease, hyperlipidemia, ≥55 years of age, hypertension, diabetes, obesity, and smoking. Women <65 years of age without a history of cardiovascular ischemic events and ≤1 cardiovascular risk factor receiving tegaserod experienced no major adverse cardiovascular event(s). Two independent, external adjudications suggest that tegaserod is safe for women <65 years of age with irritable bowel syndrome with constipation, no history of cardiovascular ischemic events, and ≤1 cardiovascular risk factor.