该研究入选患者13,600例，亚组分析结果再次肯定了最初结论（见图1、图2），并且明确了服用普拉格雷的获益与风险。Stephen D. Wiviott说：“该研究向我们传达这样一种理念，药物在阻止血小板聚集作用更强、起效最快、作用更持久的同时，也会使出血事件增加。

MACE率减少
      普拉格雷作用更迅速持久，这也就是它为何在降低MACE率同时增加了出血事件的发生。一项观察PCI术后出现各种临床事件的大规模分析显示：若患者未发生缺血事件时间持续在3天或以上时，患者就会达到一种“稳态”。同样的结果也可能会在出血事件上，“出血事件发生率上升的时间一般是在早期和晚期，甚至在患者随访期间出现。” Wiviott说。

亚组荟萃分析：糖尿病患者
      TRITON-TIMI 38亚组分析显示：糖尿病患者更容易从普拉格雷的应用中受益，因为该类患者基线血小板聚集程度高。应用普拉格雷，在不会使出血事件增加的同时， CV事件和中风率下降4.8%。

      与氯吡格雷组相比，服用普拉格雷组的糖尿病患者在联合终点MI, CVA和主要出血事件风险减少26%(HR=0.74, 0.62-0.89; P=0.001)，而在非糖尿病患者，此比例仅为8%（HR=0.92, 0.82-1.03; P=0.16）。

STEMI和MI
      在TRITON-TIMI 38研究中，共有3,434例STEMI患者行PCI术， 直接PCI有2,438例，1,094例行补救PCI。15个月时，普拉格雷组TIMI出血事件高于对照组，5.1% vs. 4.7%，HR=1.07, 0.79-1.47，P=0.65，但未达统计学意义。

Efficacy analysis 有效性分析
      Wiviott说，目前的问题是普拉格雷减少的MI率能否转换成临床事件。一项对MI事件分析得出，若服用普拉格雷导致MI减少，则患者临床事件发生率也比较小，但是围手术期发生的心梗率则不然。Wiviott在报告中指出，在普拉格雷治疗组中，围外科手术期心梗发生率为0.1%，在氯吡格雷组为0。

      TRITON-TIMI 38研究中对ACS患者药物用量已经得到了大家的支持，即300 mg首剂，之后75 mg/天或者是普拉格雷60 mg首剂，之后10 mg/天。该研究中，患者的平均随访时间是12个月，随访时间最长的是15个月。

     （医心评论：马秀芹 译  呼唤 校）

TRITON-TIMI 38: Reduction in Events, Increase in Bleeding

A recent data analysis from TRITON-TIMI 38 confirmed earlier reports of reductions in cardiac events with prasugrel vs. clopidogrel, as well as a slightly increased risk of bleeding, in patients with acute coronary syndrome undergoing PCI.

Subgroup analysis within the population of 13,600 patients enrolled in the study confirmed earlier reports (see Figures 1 and 2 for data from ESC 2008) and further defined the benefits and risks associated with prasugrel(Effient, Daiichi Sankyo and Eli Lilly) compared with clopidogrel (Plavix, Sanofi-Aventis and Bristol-Myers Squibb), according to Stephen D. Wiviott, MD, of Brigham and Women’s Hospital in Boston.

"This study largely serves as a proof of concept that more intensive, more rapid, and more consistent inhibition of platelet aggregation results in improved clinical outcomes, as well as more bleeding," he said.

According to Wiviott, prasugrel has a more rapid onset of action than clopidogrel, and it is this property that could explain both reductions in MACE and increases in bleeding events. However, a landmark analysis, looking specifically at timing of events after PCI, showed continued reduction in ischemic events past three days – a time point at which patients could be expected to reach a "steady state," according to Wiviott.

Similar results were seen in major bleeding events. "The increase in bleeding was seen both early and late, and it seems the greater dominance of the bleeding excess was seen during the follow-up period," Wiviott said.

Subgroup analysis: Patients with diabetes.

The subgroup analysis of TRITON-TIMI 38 demonstrated that patients with diabetes may derive a greater benefit with prasugrel because of higher platelet aggregation at baseline, according to Wiviott. In that population, there was a 4.8% absolute reduction in CV events or stroke and no increase in major bleeding, Wiviott said.

"It is uncertain if this finding with major bleeding was a chance finding or whether this finding with major bleeding has some biologicalplausibility," Wiviott said.

Further analysis of major and minor bleeding demonstrated a slightly increased risk in patients given prasugrel compared with clopidogrel. Patients with diabetes assigned to prasugrel had a greater risk reduction for MI than those assigned clopidogrel (HR=0.60, 0.48-0.76; P<.001) as did patients without diabetes (HR=0.82, 0.72-0.95; P=.006).

A 26% risk reduction was seen in the combined endpoint of MI, CVA, and major bleeding in diabetic patients assigned prasugrel compared with those assigned clopidogrel (HR=0.74, 0.62-0.89; P=.001) and an 8% reduction in risk for this endpoint in nondiabetic patients assigned prasugrel vs. clopidogrel (HR=0.92, 0.82-1.03; P=0.16).

STEMI and MI
A total of 3,534 patients with STEMI were enrolled in TRITON-TIMI 38 following PCI: 2,438 (69%) after primary PCI and 1,094 after secondary PCI.

Results again favored treatment with prasugrel. TIMI major or minor bleeding was more frequent in the prasugrel group (5.1% vs. 4.7% clopidogrel; HR=1.07, 0.79-1.47) at 15 months. However, the difference was not statistically significant (P=.65).

There has been concern that MIs prevented by prasugrel are largely periprocedural with questionable clinical relevance, Wiviott said. However, an efficacy analysis of MI events, broken down by ESC/ACC/AHA/WHF classifications, showed consistently lower incidence in patients assigned prasugrel with all types of MI except peri-CABG infarctions.

Wiviott reported a 0.1% cumulative incidence of peri-CABG infarctions in prasugrel-treated patients and none in clopidogrel-treated patients.

Patients in TRITON-TIMI 38 were representative of "patients across the spectrum of acute coronary syndrome" and were assigned either a 300-mg loading dose of clopidogrel plus 75 mg daily or a 60-mg loading dose of prasugrel plus 10 mg daily.

Patients were followed for a median 12 months and up to a maximum of 15 months.