Wiviott Stephen D, Braunwald Eugene, Angiolillo Dominick J, Meisel Simha, Dalby Anthony J, Verheugt Freek W A, Goodman Shaun G, Corbalan Ramon, Purdy Drew A, Murphy Sabina A, McCabe Carolyn H, Antman Elliott M
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
Circulation. 2008 Oct 14;118(16):1626-36. doi: 10.1161/CIRCULATIONAHA.108.791061. Epub 2008 Aug 31.
Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38.
We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05).
Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.
糖尿病（DM）患者在急性冠脉综合征后发生心血管事件复发的风险很高，部分原因是血小板反应性增加。心肌梗死溶栓治疗38试验（TRITON-TIMI 38）显示，与氯吡格雷相比，普拉格雷强化抗血小板治疗可使缺血事件总体减少，但出血更多。我们在TRITON-TIMI 38研究中比较了普拉格雷与氯吡格雷在糖尿病患者中的疗效。
我们根据既往糖尿病病史对13608名受试者进行分类，并进一步根据胰岛素使用情况进行分类。通过对数秩检验比较主要终点（心血管死亡、非致命性心肌梗死或非致命性卒中）和关键次要终点，包括净临床获益（死亡、非致命性心肌梗死、非致命性卒中和非致命性TIMI大出血）。我们发现3146名受试者有既往糖尿病病史，其中776人接受胰岛素治疗。在无糖尿病受试者中，普拉格雷使主要终点显著降低（9.2%对10.6%；风险比[HR]，0.86；P=0.02），在糖尿病受试者中也显著降低（12.2%对17.0%；HR，0.70；P<0.001，P（交互作用）=0.09）。在使用胰岛素的糖尿病受试者中观察到普拉格雷的益处（14.3%对22.2%；HR，0.63；P=0.009），在未使用胰岛素的糖尿病受试者中也有类似结果（11.5%对15.3%；HR，0.74；P=0.009）。在无糖尿病受试者中，普拉格雷使心肌梗死发生率降低18%（7.2%对8.7%；HR，0.82；P=0.006），在糖尿病受试者中降低40%（8.2%对13.2%；HR，0.60；P<0.001，P（交互作用）=0.02）。虽然在无糖尿病受试者中，使用普拉格雷的TIMI大出血发生率增加（1.6%对2.4%；HR，1.43；P=0.02），但在糖尿病受试者中，氯吡格雷和普拉格雷的发生率相似（2.6%对2.5%；HR，1.06；P=0.81，P（交互作用）=0.29）。与无糖尿病受试者相比（11.5%对12.3%；HR，0.92；P=0.16，P（交互作用）=0.05），普拉格雷对糖尿病受试者的净临床获益更大（14.6%对19.2%；HR，0.74；P=0.001）。
糖尿病受试者缺血事件的减少幅度往往更大，且未观察到TIMI大出血增加，因此与氯吡格雷相比，普拉格雷的净治疗获益更大。这些数据表明，普拉格雷提供的强化口服抗血小板治疗对糖尿病患者特别有益。
