Cardiovascular Safety During and After Use of Phentermine and Topiramate

• Published in: The journal of clinical endocrinology and metabolism 2019-02, Vol.104 (2), p.513-522
• Main Authors: Ritchey, Mary E, Harding, Abenah, Hunter, Shannon, Peterson, Craig, Sager, Philip T, Kowey, Peter R, Nguyen, Lan, Thomas, Steven, Cainzos-Achirica, Miguel, Rothman, Kenneth J, Andrews, Elizabeth B, Anthony, Mary S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-obesity agents; Anti-Obesity Agents - adverse effects; Anticonvulsants; Cerebral infarction; Clinical s; Combination drug therapy; Drug Combinations; Drug dosages; Drugs; Female; Heart attack; Heart rate; Heart Rate - drug effects; Hospitalization - statistics & numerical data; Humans; Incidence; Male; Middle Aged; Myocardial infarction; Myocardial Infarction - chemically induced; Myocardial Infarction - epidemiology; Myocardial Infarction - therapy; Nervous system agents; Obesity - drug therapy; Patients; Phentermine; Phentermine - adverse effects; Retrospective Studies; Stroke; Stroke - chemically induced; Stroke - epidemiology; Stroke - therapy; Topiramate; Topiramate - adverse effects; Weight Loss - drug effects; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-01010

Abstract Context Increases in heart rate were seen during the clinical program for fixed-dose combination phentermine (PHEN) and topiramate (TPM), an oral medication indicated for weight management; however, the effect on cardiovascular (CV) outcomes is uncertain. Objective The aim of the present study was to determine the extent to which the rates of major adverse CV events (MACE) in patients using PHEN and TPM (including fixed dose) differed from the MACE rates during unexposed periods. Design Retrospective cohort study. Setting MarketScan, US insurance billing data. Patients or Other Participants Patients aged >18 years with ≥6 months of continuous enrollment in the database before taking PHEN and/or TPM or after stopping these medications. Interventions PHEN and TPM, taken separately and together (including fixed dose). Main Outcome Measures MACE, a composite of hospitalization for acute myocardial infarction and stroke and in-hospital CV death. Results Because the outcomes are rare and the duration of medication use was brief, few events occurred. The MACE rates among current users of PHEN/TPM, fixed-dose PHEN/TPM, and PHEN were lower than those among unexposed former users. In contrast, the rate of MACE among current users of TPM was greater than among unexposed former users [incidence rate ratio: PHEN/TPM, 0.57; 95% CI, 0.19 to 1.78; fixed-PHEN/TPM, 0.24; 95% CI, 0.03 to 1.70; PHEN, 0.56; 95% CI, 0.34 to 0.91; TPM, 1.58; 95% CI, 1.33 to 1.87). Conclusions Overall, the data indicated no increased risk of MACE for current PHEN/TPM users; however, the 95% CIs for the PHEN/TPM groups were broad, indicating that the data were compatible with a wide range of possible values. In the present retrospective cohort safety study, the current users of combination phentermine and topiramate did not have an increased incidence rate of MACEs compared with former users.