Prospective Postmarketing Surveillance of Acute Myocardial Infarction in New Users of Saxagliptin: A Population-Based Study

Autor: Sengwee, Toh, Marsha E, Reichman, David J, Graham, Christian, Hampp, Rongmei, Zhang, Melissa G, Butler, Aarthi, Iyer, Malcolm, Rucker, Madelyn, Pimentel, Jack, Hamilton, Samuel, Lendle, Bruce H, Fireman, Connie Mah, Trinacty
Rok vydání: 2017
Předmět:
Male
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism

Myocardial Infarction
Postmarketing surveillance
Adamantane
030204 cardiovascular system & hematology
Saxagliptin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Internal Medicine
medicine
Product Surveillance
Postmarketing

Humans
Hypoglycemic Agents
030212 general & internal medicine
Prospective Studies
Propensity Score
Proportional Hazards Models
Advanced and Specialized Nursing
Dipeptidyl-Peptidase IV Inhibitors
Pioglitazone
Proportional hazards model
business.industry
Incidence
Hazard ratio
Sitagliptin Phosphate
Dipeptides
Middle Aged
Interim analysis
United States
Insulin
Long-Acting

Sulfonylurea Compounds
chemistry
Sitagliptin
Propensity score matching
Acute Disease
Cardiology
Female
Thiazolidinediones
business
medicine.drug
Follow-Up Studies
Zdroj: Diabetes care. 41(1)
ISSN: 1935-5548
Popis: OBJECTIVE The cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS We identified patients aged ≥18 years, starting from the approval date of saxagliptin in 2009 and continuing through August 2014, using data from 18 Mini-Sentinel data partners. We conducted seven sequential assessments comparing saxagliptin separately with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin, using disease risk score (DRS) stratification and propensity score (PS) matching to adjust for potential confounders. Sequential testing kept the overall chance of a false-positive signal below 0.05 (one-sided) for each pairwise comparison. RESULTS We identified 82,264 saxagliptin users and more than 1.5 times as many users of each comparator. At the end of surveillance, the DRS-stratified hazard ratios (HRs) (95% CI) were 1.08 (0.90–1.28) in the comparison with sitagliptin, 1.11 (0.87–1.42) with pioglitazone, 0.79 (0.64–0.98) with sulfonylureas, and 0.57 (0.46–0.70) with long-acting insulin. The corresponding PS-matched HRs were similar. Only one interim analysis of 168 analyses met criteria for a safety signal: the PS-matched saxagliptin-pioglitazone comparison from the fifth sequential analysis, which yielded an HR of 1.63 (1.12–2.37). This association diminished in subsequent analyses. CONCLUSIONS We did not find a higher AMI risk in saxagliptin users compared with users of other selected antihyperglycemic agents during the first 5 years after U.S. Food and Drug Administration approval of the drug.
Databáze: OpenAIRE