Canagliflozin may increase thromboembolic events in males with erythrocytosis but not in females.

SGLT2 inhibitor-induced erythropoiesis may increase blood viscosity and precipitate thromboembolism, particularly in patients with preexisting erythrocytosis.

SGLT2抑制剂诱导的红细胞生成可能会增加血液粘度并诱发血栓栓塞，特别是在已有红细胞增多症的患者中。

We conducted a post hoc pooled analysis of patient-level data from the randomized, double-blind, placebo-controlledCanagliflozin Cardiovascular Assessment Study program and the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial, which assessed the safety and efficacy of canagliflozin in patients with type 2 diabetes mellitus.

我们对Canagliflozin心血管评估研究计划和Canagliflozin与糖尿病已知肾病临床评估试验中的患者级数据进行了事后汇总分析，这两项研究均为随机、双盲、安慰剂对照试验，评估了Canagliflozin在2型糖尿病患者中的安全性和有效性。

The primary outcome, a composite of myocardial infarction (MI), stroke, and any thromboembolism, was evaluated using sex-specific Cox models, with baseline hematocrit as an effect modifier.

主要结果是一个复合结果，包括心肌梗死(MI)、中风和任何血栓栓塞事件，使用性别特异性的Cox模型进行评估，基线血细胞比容作为效应修饰因子。

Among participants with available baseline hematocrit values (98.5% [14 321/14 543]), 35% were female.

在有基线血细胞比容值的参与者中（98.5% [14 321/14 543]），35%为女性。

Canagliflozin significantly increased hematocrit levels compared with placebo even in patients with erythrocytosis (males > 49%; females > 48%) and increased the proportion of individuals with erythrocytosis at 1 year (males, 16.9% vs 5.5%; females, 5.2% vs 1.0%).

即使在红细胞增多症患者中（男性>49%；女性>48%），卡格列净也显著提高了血细胞比容水平，与安慰剂相比，并在1年内增加了红细胞增多症个体的比例（男性，16.9% vs 5.5%；女性，5.2% vs 1.0%）。

Overall, canagliflozin did not alter the risk of the primary outcome in either males or females.

总体而言，卡格列净并未改变男性或女性主要结果的风险。

However, in males, baseline hematocrit levels modified the treatment effect on the primary outcome, whether assessed categorically (anemia, normal, and erythrocytosis) or continuously with fractional polynomial (FP) analysis (P interaction < .05).

然而，在男性中，基线血细胞比容水平改变了卡格列净对主要结果的治疗效果，无论是通过分类评估（贫血、正常和红细胞增多症）还是通过分数多项式（FP）分析连续评估（P交互作用< .05）。

FP analysis showed treatment benefits in anemic males but show harm in those with erythrocytosis, primarily driven by an increased risk of MI.

FP分析显示，在贫血男性中治疗有益，但在红细胞增多症患者中显示出危害，主要由心肌梗死风险增加所驱动。

Meanwhile, no heterogeneity was seen in females for these outcomes.

同时，这些结果在女性中未显示出异质性。

In conclusion, canagliflozin may pose a safety concern for thromboembolism in males with erythrocytosis at baseline, warranting further investigations.

总之，对于基线时有红细胞增多症的男性患者，卡格列净可能对血栓栓塞构成安全风险，需要进一步调查。

These trials were registered at www.ClinicalTrials.gov as #NCT01032629, #NCT01989754, and #NCT02065791.

这些试验已在www.ClinicalTrials.gov上注册，注册号为#NCT01032629、#NCT01989754和#NCT02065791。