Cardiovascular Safety During and After Use of Phentermine and Topiramate.

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.