Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System

Abstract Background and aims We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). Methods FAERS data reporting HF and DPP-4-Is use in the period...

Full description

Saved in:
Bibliographic Details
Published in:Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2016-05, Vol.26 (5), p.380-386
Main Authors: Raschi, E, Poluzzi, E, Koci, A, Antonazzo, I.C, Marchesini, G, De Ponti, F
Format: Article
Language:English
Subjects:
Adamantane - adverse effects
Adamantane - analogs & derivatives
Adolescent
Adult
Adverse Drug Reaction Reporting Systems
Aged
Biomarkers - blood
Blood Glucose - drug effects
Blood Glucose - metabolism
Cardiovascular
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - enzymology
Dipeptides - adverse effects
Dipeptidyl Peptidase 4 - metabolism
Dipeptidyl peptidase-4 inhibitors
Dipeptidyl-Peptidase IV Inhibitors - adverse effects
Disproportionality
Drug safety
Europe - epidemiology
FAERS
Female
Heart failure
Heart Failure - chemically induced
Heart Failure - diagnosis
Heart Failure - epidemiology
Humans
Japan - epidemiology
Male
Middle Aged
Retrospective Studies
Risk Assessment
Risk Factors
Saxagliptin
Sitagliptin
Sitagliptin Phosphate - adverse effects
Spontaneous reporting system
Time Factors
Treatment Outcome
United States - epidemiology
United States Food and Drug Administration
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background and aims We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). Methods FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query “Cardiac failure”. Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders. Results HF during DPP4-I use was recorded in 390 reports (4.4% of total reports). In exploratory analysis, statistically significant ROR emerged for DPP-4-I as a class (ROR = 1.17; 95% CI = 1.05–1.29), saxagliptin (1.68; 1.29–2.17), vildagliptin (2.39; 1.38–4.14), and rosiglitazone (13.98; 13.30–14.70). In consolidated analyses, the ROR for saxagliptin (2.60; 1.92–3.50) and vildagliptin (4.07; 2.28–7.27) increased, and became also significant for sitagliptin (1.61; 1.40–1.86). Concomitant drugs were reported in more than 50% of cases; the adjusted RORs of saxagliptin (2.30; 1.70–3.10), vildagliptin (3.15; 1.76–5.63), and sitagliptin (1.48; 1.28–1.71) were nonetheless significant. Conclusion FAERS data are consistent with clinical studies on a possible association between saxagliptin and HF. The disproportionate reporting of HF with sitagliptin, conflicting with a recent phase IV trial, suggests that cardiovascular safety requires close post-marketing vigilance by clinicians of individual DPP-4-I in the community until the issue of class effect is solved.
ISSN:0939-4753
1590-3729
DOI:10.1016/j.numecd.2016.02.006