Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA
Sinai Health System and Department of Medicine, University of Toronto, Toronto, ON, Canada.
BMJ. 2020 Aug 25;370:m2812. doi: 10.1136/bmj.m2812.
To estimate the rate of lower limb amputation among adults newly prescribed canagliflozin according to age and cardiovascular disease.
Population based, new user, cohort study.
Two commercial and Medicare claims databases, 2013-17.
Patients newly prescribed canagliflozin were propensity score matched 1:1 with patients newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. Hazard ratios and rate differences per 1000 person years were computed for the rate of lower limb amputation in the following four groups: group 1, patients aged less than 65 years without baseline cardiovascular disease; group 2, patients aged less than 65 with baseline cardiovascular disease; group 3, patients aged 65 or older without baseline cardiovascular disease; group 4, patients aged 65 or older with baseline cardiovascular disease. Within each group, pooled hazard ratio and rate difference per 1000 person years were calculated by meta-analysis.
Canagliflozin versus a GLP-1 agonist.
Lower limb amputation requiring surgery.
Across the three databases, 310 840 propensity score matched adults who started canagliflozin or a GLP-1 agonist were identified. The hazard ratio and rate difference per 1000 person years for amputation in adults receiving canagliflozin compared with a GLP-1 agonist for each group was: group 1, hazard ratio 1.09 (95% confidence interval 0.83 to 1.43), rate difference 0.12 (-0.31 to 0.55); group 2, hazard ratio 1.18 (0.86 to 1.62), rate difference 1.06 (-1.77 to 3.89); group 3, hazard ratio 1.30 (0.52 to 3.26), rate difference 0.47 (-0.73 to 1.67); and group 4, hazard ratio 1.73 (1.30 to 2.29), rate difference 3.66 (1.74 to 5.59).
The increase in rate of amputation with canagliflozin was small and most apparent on an absolute scale for adults aged 65 or older with baseline cardiovascular disease, resulting in a number needed to treat for an additional harmful outcome of 556 patients at six months (that is, 18 more amputations per 10 000 people who received canagliflozin). These results help to contextualize the risk of amputation with canagliflozin in routine care.
根据年龄和心血管疾病，估计新处方卡格列净的成年人下肢截肢率。
基于人群的新用户队列研究。
2013-17 年两个商业和医疗保险索赔数据库。
新处方卡格列净的患者与新处方胰高血糖素样肽-1（GLP-1）受体激动剂的患者进行倾向评分匹配 1:1。计算以下四个组中下肢截肢的发生率比和每 1000 人年的差异率：组 1，年龄小于 65 岁且无基线心血管疾病的患者；组 2，年龄小于 65 岁且有基线心血管疾病的患者；组 3，年龄 65 岁或以上且无基线心血管疾病的患者；组 4，年龄 65 岁或以上且有基线心血管疾病的患者。在每个组中，通过荟萃分析计算每 1000 人年的 pooled 风险比和差异率。
卡格列净与 GLP-1 激动剂。
需要手术的下肢截肢。
在三个数据库中，确定了 310840 名接受卡格列净或 GLP-1 激动剂治疗的新处方成年人进行倾向评分匹配。接受卡格列净治疗的成年人与接受 GLP-1 激动剂治疗的成年人相比，每个组的截肢发生率的风险比和每 1000 人年的差异率为：组 1，风险比 1.09（95%置信区间 0.83 至 1.43），差异率 0.12（-0.31 至 0.55）；组 2，风险比 1.18（0.86 至 1.62），差异率 1.06（-1.77 至 3.89）；组 3，风险比 1.30（0.52 至 3.26），差异率 0.47（-0.73 至 1.67）；组 4，风险比 1.73（1.30 至 2.29），差异率 3.66（1.74 至 5.59）。
卡格列净导致的截肢率增加很小，在有基线心血管疾病的 65 岁或以上成年人中，绝对规模最为明显，导致每治疗 556 例额外不良结局的需要治疗数为 6 个月（即接受卡格列净治疗的 10000 人中每 18 人就会有更多的截肢）。这些结果有助于在常规护理中了解卡格列净截肢的风险。
