高剂量西他列汀与老年慢性肾脏病患者充血性心力衰竭风险的关系。
Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKD.
机构信息
ICES, Kidney, Dialysis and Transplantation Research Program, Ontario, Canada.
Department of Epidemiology and Biostatistics, Western University, London, Canada.
出版信息
Clin J Am Soc Nephrol. 2020 Dec 7;15(12):1728-1739. doi: 10.2215/CJN.08310520. Epub 2020 Nov 25.
BACKGROUND AND OBJECTIVES
Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is commonly prescribed to patients with 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. We compare the 1-year risk of death or hospitalization with congestive heart failure in patients with CKD newly prescribed sitagliptin at >50 versus ≤50 mg/d.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This population-based cohort study included older adults (>66 years) with type 2 diabetes and an eGFR<45 ml/min per 1.73 m (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 intervals were obtained using bootstrap variance estimators.
RESULTS
Of 9215 patients, 6518 started sitagliptin at >50 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 >50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, -0.12%; 95% confidence interval, -0.19 to -0.06) and a lower risk of all-cause 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 >50 versus ≤50 mg/d.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_25_CJN08310520_final.mp3.
背景和目的
西他列汀是一种二肽基肽酶-4 抑制剂，常用于治疗 2 型糖尿病患者。由于该药物主要通过肾脏排泄，因此建议慢性肾脏病患者减少剂量。一些证据表明，西他列汀与充血性心力衰竭的风险增加有关，尤其是在较高剂量时。我们比较了新开始服用西他列汀>50 毫克/天和≤50 毫克/天的慢性肾脏病患者在 1 年内因充血性心力衰竭而死亡或住院的风险。
设计、地点、参与者和测量：这项基于人群的队列研究纳入了 2010 年至 2017 年间在加拿大安大略省新开始服用西他列汀的年龄>66 岁且估算肾小球滤过率<45 ml/min/1.73 m（但未接受透析）的 2 型糖尿病患者。我们基于倾向评分进行逆概率治疗加权，以平衡基线特征。主要复合结局为充血性心力衰竭所致死亡或住院。次要结局包括胰腺炎或低血糖所致住院、全因住院和血糖控制。使用 Cox 比例风险回归获得加权风险比，使用自举方差估计器获得 95%置信区间。
结果
在 9215 名患者中，6518 名患者开始服用西他列汀>50 毫克/天，2697 名患者开始服用西他列汀≤50 毫克/天。两组 1 年内因充血性心力衰竭而死亡或住院的风险无显著差异（每 1000 人年 79 例与 126 例；加权风险比，0.88；95%置信区间，0.67 至 1.14）；胰腺炎（加权风险比，0.98；95%置信区间，0.32 至 3.03）和低血糖（加权风险比，1.10；95%置信区间，0.64 至 1.90）住院也无显著差异。开始服用西他列汀>50 毫克/天的患者糖化血红蛋白浓度均值较低（组间加权差异，-0.12%；95%置信区间，-0.19 至-0.06），全因住院风险较低（加权风险比，0.81；95%置信区间，0.66 至 0.98）。
结论
在开始服用西他列汀>50 毫克/天和≤50 毫克/天的慢性肾脏病老年患者中，死亡或充血性心力衰竭的风险无差异。
播客
本文包含一个播客，网址为 https://www.asn-online.org/media/podcast/CJASN/2020_11_25_CJN08310520_final.mp3。
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