Higher-dose sitagliptin and the risk of congestive heart failure in older adults with CKD

Background and objectives Sitagliptin, a dipeptidylpeptidase-4 inhibitor, is commonlyprescribed to patientswith type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses.Wecompare the 1-year risk of death or hospitalizationwith congestive heart failure in patients with CKD newly prescribed sitagliptin at \u3c50 versus ≤50 mg/d. Design, setting, participants, & measurements This population-based cohort study included older adults (\u3e66 years) with type 2 diabetes and an eGFR\u3c45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95%confidence intervalswere obtained using bootstrap variance estimators. Results Of 9215 patients, 6518 started sitagliptin at \u3e50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at \u3e50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, 20.12%; 95% confidence interval, 20.19 to 20.06) and a lower risk of allcause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98). Conclusions The risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at \u3e50 versus ≤50 mg/d

Clinical outcomes of failing to dose-reduce cephalosporin antibiotics in older adults with CKD

Background and objectives Current dosing recommendations for cephalosporin antibiotics are on the basis of pharmacokinetic studies and are frequently ignored in practice. This study was undertaken to investigate the clinical outcomes of failing to dose-reduce cephalosporin antibiotics in CKD. Design, setting, participants, &amp; measurements Retrospective cohort study conducted in Ontario, Canada using linkedpopulation-based health care databases. Nine thousand three hundred forty-sevenoutpatients (median age 83; interquartile range, 77-88 years; 57% women) with an eGFR>30 ml/min per 1.73 m2 and no prior history of dialysis were dispensed oral cephalexin, cefuroxime, or cefprozil between April of 2007 andMarch of 2016. Two thirds of the patients (6253 of 9347) received a higher than recommended daily dose of cephalexin (>1000 mg), cefuroxime ((>500mg), or cefprozil ((>500mg). The primary outcome was a hospital encounter (emergency room visit or hospital admission)with a condition listed as a possible side-effect of cephalosporins. Secondary outcomes were antibiotic treatment failure and all-cause mortality. All measures were assessed in the 30 days after cephalosporin initiation. Results Patients who received a higher than recommended dose of a cephalosporin antibiotic were similar in multiple indicators of baseline health to patientswho received a reduced dose. Overall, 6% of patients presented to hospitalwith a possible cephalosporin side-effect, 13%failed antibiotic treatment, and 3% died. Compared with a reduced dose, receiving a higher dose of antibiotic was not associated with a different rate of side-effects (adjusted odds ratio, 1.00; 95% confidence interval, 0.84 to 1.20), treatment failure (1.01; 0.88 to 1.15), or death (0.99; 0.76 to 1.29). Conclusions In this study we failed to demonstrate any association between the dose of cephalosporin antibiotic administered to elderly patients with CKD and the risk of side-effects leading to hospitalization, treatment failure, or mortality.</p