Medizinische Klinik III der Universität zu Köln, Köln, Germany.
J Diabetes. 2010 Sep;2(3):212-20. doi: 10.1111/j.1753-0407.2010.00082.x.
Patients with Type 2 diabetes mellitus (T2DM) are often treated with multiple glucose-lowering and cardiovascular agents. The concomitant use of nitrates, renin-angiotensin system (RAS) blockers, or insulin has been linked to a potential increase in myocardial ischemic risk with rosiglitazone. The PROactive database provides an opportunity to investigate the effects of these medications on the potential macrovascular benefits reported with pioglitazone.
The PROactive study was a randomized double-blind prospective trial that evaluated mortality and cardiovascular morbidity in 5238 patients with T2DM and macrovascular disease. Patients received pioglitazone or placebo in addition to their baseline glucose-lowering and cardiovascular medications. The effect of pioglitazone on composite endpoints was evaluated, including all-cause death, myocardial infarction (MI), and stroke, as well as safety events of edema and serious heart failure, in subgroups using nitrates, RAS blockers, or insulin at baseline.
The risk of all-cause death, MI, and stroke for pioglitazone versus placebo was similar regardless of the baseline use of nitrates, RAS blockers, or insulin, with hazard ratios ranging from 0.81 to 0.87. Similar results were obtained for the other composite endpoints analyzed. There were no significant interactions between baseline medication subgroups and treatment. The increased risk of edema and serious heart failure was consistent across the baseline medication subgroups.
This post hoc analysis did not reveal an increased risk of macrovascular events with pioglitazone in patients receiving nitrates, RAS blockers, or insulin. Rather, all patients realized the same trend towards benefit with pioglitazone, and adverse events of edema and heart failure were predictable.
2 型糖尿病（T2DM）患者通常需要使用多种降糖和心血管药物进行治疗。与罗格列酮相比，同时使用硝酸盐、肾素-血管紧张素系统（RAS）阻滞剂或胰岛素与心肌缺血风险增加有关。PROactive 数据库提供了一个机会，可以研究这些药物对吡格列酮潜在的大血管益处的影响。
PROactive 研究是一项随机、双盲、前瞻性试验，评估了 5238 例患有 T2DM 和大血管疾病的患者的死亡率和心血管发病率。患者在基线降糖和心血管药物治疗的基础上接受吡格列酮或安慰剂治疗。评估了吡格列酮对复合终点的影响，包括全因死亡、心肌梗死（MI）和中风，以及基线使用硝酸盐、RAS 阻滞剂或胰岛素的亚组中的水肿和严重心力衰竭的安全事件。
吡格列酮与安慰剂相比，全因死亡、MI 和中风的风险相似，无论基线使用硝酸盐、RAS 阻滞剂或胰岛素，风险比范围为 0.81 至 0.87。分析的其他复合终点也得到了类似的结果。基线药物亚组和治疗之间没有显著的交互作用。水肿和严重心力衰竭的风险在基线药物亚组中是一致的。
这项事后分析并未显示接受硝酸盐、RAS 阻滞剂或胰岛素的患者使用吡格列酮会增加大血管事件的风险。相反，所有患者都实现了吡格列酮相同的获益趋势，并且水肿和心力衰竭等不良事件是可预测的。
