Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors and Sudden Cardiac Arrest and Ventricular Arrhythmia: Population-Based Cohort Studies.
Adamantane
/ adverse effects
Administrative Claims, Healthcare
Aged
Arrhythmias, Cardiac
/ chemically induced
Cohort Studies
Databases, Factual
Death, Sudden, Cardiac
/ epidemiology
Dipeptides
/ adverse effects
Dipeptidyl-Peptidase IV Inhibitors
/ adverse effects
Female
Humans
Kaplan-Meier Estimate
Linagliptin
/ adverse effects
Male
Middle Aged
Proportional Hazards Models
Sitagliptin Phosphate
/ adverse effects
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
20
04
2021
accepted:
21
07
2021
pubmed:
1
8
2021
medline:
23
2
2022
entrez:
31
7
2021
Statut:
ppublish
Résumé
In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase-4 inhibitors, but evidence from population-based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high-dimensional propensity score (hdPS) matched, new-user cohort studies. We analyzed Medicaid and Optum Clinformatics separately. We identified new users of saxagliptin, sitagliptin (both databases), and linagliptin (Optum only). We defined SCA/VA outcomes using emergency department and inpatient diagnoses. We identified and then controlled for confounders via a data-adaptive, hdPS approach. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar year. We identified the following matched comparisons: saxagliptin vs. sitagliptin (23,895 vs. 96,972) in Medicaid, saxagliptin vs. sitagliptin (48,388 vs. 117,383) in Optum, and linagliptin vs. sitagliptin (36,820 vs. 78,701) in Optum. In Medicaid, use of saxagliptin (vs. sitagliptin) was associated with an increased rate of SCA/VA (adjusted HR (aHR), 2.01, 95% confidence interval (CI) 1.24-3.25). However, in Optum data, this finding was not present (aHR, 0.79, 95% CI 0.41-1.51). Further, we found no association between linagliptin (vs. sitagliptin) and SCA/VA (aHR, 0.65, 95% CI 0.36-1.17). We found discordant results regarding the association between SCA/VA with saxagliptin compared with sitagliptin in two independent datasets. It remains unclear whether these findings are due to heterogeneity of treatment effect in the different populations, chance, or unmeasured confounding.
Identifiants
pubmed: 34331322
doi: 10.1002/cpt.2381
pmc: PMC9450482
mid: NIHMS1823271
doi:
Substances chimiques
Dipeptides
0
Dipeptidyl-Peptidase IV Inhibitors
0
Linagliptin
3X29ZEJ4R2
saxagliptin
9GB927LAJW
Adamantane
PJY633525U
Sitagliptin Phosphate
TS63EW8X6F
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
227-242Subventions
Organisme : NHLBI NIH HHS
ID : F32 HL154519
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA048001
Pays : United States
Organisme : Patient Centered Outcomes Research Institute
ID : CER-2017C3-9230
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060975
Pays : United States
Organisme : National Cancer Institute: P30CA008748
Organisme : NIA NIH HHS
ID : R01 AG064589
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM075766
Pays : United States
Organisme : American Diabetes Association
ID : 1-18-ICTS-097
Organisme : NIA NIH HHS
ID : R01 AG025152
Pays : United States
Informations de copyright
© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.
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