PURPOSE: In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance on investigating cardiovascular risk with oral diabetic drugs, including dipeptidyl peptidase-4 inhibitors (DPP-4i). In 2014, underpowered, post hoc analyses of clinical trials suggested an increased risk of heart failure with the use of these products. As such, we assessed disproportionate reporting of major adverse cardiac events (MACE) among reports for DPP-4i submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.
METHODS: We assessed the empirical Bayes geometric mean (EBGM) and its lower bound (EB05) of the relative reporting ratio for MACE among DPP-4i reports in the full FAERS database and in a subset of reports limited to cardiovascular and diabetic drugs. We then compared the EB05 in these 2 analyses and calculated the percent positive agreement for signals of disproportional reporting (SDRs) involving MACE.
RESULTS: Of 180.3 million adverse event reports, 13.4 million were for diabetic and cardiovascular drugs. In the cardiovascular subset, there was an SDR for heart failure with linagliptin (EB05 = 2782.47) and saxagliptin (EB05 = 2.40), myocardial infarction with alogliptin (EB05 = 290.11), and cerebral infarction with sitagliptin (EB05 = 2.80). Of the 14 MACE, 8 had a percent positive agreement >/=50% for an SDR in both analyses. Overall, the cardiovascular subset elicited 11 more SDRs for DPP-4i than the full dataset.
CONCLUSIONS: Postmarketing surveillance of DPP-4i through FAERS suggest increased reporting of MACE, supporting the current FDA warning of heart failure risk. This suggests the need for additional longitudinal, observational research into the association of DPP-4i and other MACE.
|投稿者||Baksh, Sheriza N; McAdams-DeMarco, Mara; Segal, Jodi B; Alexander, G Caleb|
|ジャーナル名||Pharmacoepidemiology and drug safety|
|組織名||Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,;Baltimore, MD, USA.;Center for Drug Safety and Effectiveness, Johns Hopkins University, Baltimore,;MD, USA.;Department of Health Policy and Management, Johns Hopkins Bloomberg School of;Public Health, Baltimore, MD, USA.;Center for Health Services and Outcomes Research, Johns Hopkins University,;Division of General Internal Medicine, Department of Medicine, Johns Hopkins;Medicine, Baltimore, MD, USA.|