{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:32:03Z","timestamp":1759177923312,"version":"3.37.3"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Johns Hopkins Center of Excellence in Regulatory Science and Innovation","award":["U01 FD004977-03"],"award-info":[{"award-number":["U01 FD004977-03"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance on investigating cardiovascular risk with oral diabetic drugs, including dipeptidyl peptidase\u20104 inhibitors (DPP\u20104i). 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\u20104i submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the empirical Bayes geometric mean (EBGM) and its lower bound (EB05) of the relative reporting ratio for MACE among DPP\u20104i 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u00a0=\u00a02782.47) and saxagliptin (EB05\u00a0=\u00a02.40), myocardial infarction with alogliptin (EB05\u00a0=\u00a0290.11), and cerebral infarction with sitagliptin (EB05\u00a0=\u00a02.80). Of the 14 MACE, 8 had a percent positive agreement \u226550% for an SDR in both analyses. Overall, the cardiovascular subset elicited 11 more SDRs for DPP\u20104i than the full dataset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Postmarketing surveillance of DPP\u20104i 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\u20104i and other MACE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4437","type":"journal-article","created":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T23:27:41Z","timestamp":1523748461000},"page":"660-667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cardiovascular safety signals with dipeptidyl peptidase\u20104 inhibitors: <scp>A<\/scp> disproportionality analysis among high\u2010risk patients"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8341-860X","authenticated-orcid":false,"given":"Sheriza N.","family":"Baksh","sequence":"first","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"},{"name":"Center for Drug Safety and Effectiveness Johns Hopkins University  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"McAdams\u2010DeMarco","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"},{"name":"Center for Drug Safety and Effectiveness Johns Hopkins University  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jodi B.","family":"Segal","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"},{"name":"Department of Health Policy and Management Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"},{"name":"Center for Drug Safety and Effectiveness Johns Hopkins University  Baltimore MD USA"},{"name":"Center for Health Services and Outcomes Research Johns Hopkins University  Baltimore MD USA"},{"name":"Division of General Internal Medicine, Department of Medicine Johns Hopkins Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Caleb","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health  Baltimore MD USA"},{"name":"Center for Drug Safety and Effectiveness Johns Hopkins University  Baltimore MD USA"},{"name":"Division of General Internal Medicine, Department of Medicine Johns Hopkins Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,14]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Centers for Disease Control and Prevention.National Diabetes Statistics Report 2017. 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