Aims/hypothesis

Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.

Methods

Data from the Angiotensin II Antagonist Losartan Study (RENAAL) and Irbesartan type II Diabetic Nephropathy Trial (IDNT) were used. The kidney outcome was time to first event of end-stage kidney disease or doubling of serum creatinine. The cardiovascular outcome was time to first event of a composite of stroke, myocardial infarction, cardiovascular death or hospitalisation for heart failure. Sex differences were assessed by a sex × treatment interaction term in Cox proportional hazards models.

Results

Included were 1737 male participants and 924 female participants. The beneficial effect of angiotensin receptor blockers on the kidney outcome was similar between male and female participants (HR in male participants 0.72 [95% CI 0.59, 0.86] vs HR in female participants 0.86 [95% CI 0.69, 1.06]; sex × treatment interaction HR 1.19 [95% CI 0.89, 1.59]). For the cardiovascular outcome, angiotensin receptor blockers lowered the risk in male but not in female participants (HR in male participants 0.81 [95% CI 0.69, 0.95] vs HR in female participants 1.11 [95% CI 0.88, 1.40]; sex × treatment interaction HR 1.37 [95% CI 1.03, 1.82]).

Conclusions/interpretation

This study in individuals with type 2 diabetes and diabetic kidney disease suggests that the beneficial effects of angiotensin receptor blockers are similar in male and female participants for the kidney outcome but not for the cardiovascular outcome. More attention to sex differences in angiotensin receptor blockers’ efficacy and underlying mechanisms of differences in response is needed.

Trial registration

ClinialTrials.gov NCT00308347

Graphical Abstract

中文翻译：

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血管紧张素受体阻滞剂对 2 型糖尿病和糖尿病肾病患者肾脏和心血管结局疗效的性别差异：RENAAL 和 IDNT 试验的事后分析

 目标/假设

我们的目的是评估血管紧张素受体阻滞剂（即氯沙坦和厄贝沙坦）对 2 型糖尿病和糖尿病肾病患者肾脏和心血管结局疗效的性别差异。

 方法

使用来自血管紧张素 II 拮抗剂氯沙坦研究 （RENAAL） 和厄贝沙坦 II 型糖尿病肾病试验 （IDNT） 的数据。肾脏结局是终末期肾病或血清肌酐加倍的首次事件发生时间。心血管结局是中风、心肌梗死、心血管死亡或因心力衰竭住院的复合事件的首次发生时间。在 Cox 比例风险模型中，通过性别×治疗交互项评估性别差异。

 结果

包括 1737 名男性参与者和 924 名女性参与者。血管紧张素受体阻滞剂对肾脏结局的有益影响在男性和女性参与者之间相似（男性参与者的 HR 为 0.72 [95% CI 0.59， 0.86] 与女性参与者的 HR 为 0.86 [95% CI 0.69， 1.06];性×治疗相互作用的 HR 1.19 [95% CI 0.89， 1.59]）。对于心血管结局，血管紧张素受体阻滞剂降低了男性受试者的风险，但没有降低女性受试者的风险（男性受试者的 HR 为 0.81 [95% CI 0.69， 0.95] 与女性受试者的 HR 为 1.11 [95% CI 0.88， 1.40];性×治疗相互作用的 HR 为 1.37 [95% CI 1.03， 1.82]）。

结论/解释

这项针对 2 型糖尿病和糖尿病肾病患者的研究表明，血管紧张素受体阻滞剂对男性和女性参与者的肾脏结果有益作用相似，但对心血管结果的有益作用则不相似。需要更多地关注血管紧张素受体阻滞剂疗效的性别差异和反应差异的潜在机制。

 试用注册

ClinialTrials.gov NCT00308347

 图形摘要