New antiplatelet therapy improves outcomes

　　奥兰多11月4日——根据2007AHA会议公布的一项最新临床试验显示，PCI术后应用抗血小板药物prasugrel比目前标准疗法更有效果。

　　在通过PCI术打开阻塞的冠状动脉的急性冠脉综合征患者，应用双重抗血小板药物即阿司匹林再加一种抗血小板药物是减少心脏病发作或者支架内血栓并发症的标准疗法。

　　TRITON-TIMI 38是大型国际双盲3期临床试验，比较单剂量给药prasugrel（一种新型抗血小板药物）和氯吡格雷（一种普通的抗血小板药物）的疗效。这两种药物都属于噻吩并吡啶类。

　　哈佛大学医学院，Samuel A. Levine Unit，波士顿女子医院主任Elliott M. Antman, M.D说，“在这样的剂量下，Prasugrel显示出更连续、更迅速的作用，与标准的通过批准剂量的氯吡格雷具有连续作用”

　　TRITON - TIMI 38研究 入选13,608名患有中高度ACS风险拟行PCI的患者。随机在30个国家707个中心筛选患者。PCI术后15个月内，给与患者prasugrel（一次负荷剂量60mg，维持每日10mg给药）或者氯吡格雷（300mg负荷剂量和维持每日75mg给药）

　　主要临床终点（心源性死亡、心脏病发作或卒中）,Prasugrel组明显降低（12.1%随机分到氯吡格雷组患者，9.9%随机分到prasugrel组的患者（HR0.81[0.73-0.90]）P=0.0004），符合最初优越性假设。Prasugrel显著降低了支架血栓的发生率，（HR0.48[0.36-0.64]，P<0.0001）、急性目标血管重建率（HR0.66[0.54-0.81]，P <0.0001）及心脏病发作率（HR0.76[0.67-0.85]，P<0.0001）。大出血在prasugrel组明显偏高（2.4%比1.8%氯吡格雷组HR1.32[1.03-1.68]P=0.03），但是prasugrel更具有效性与安全性，净临床获益（全因死亡，非致命性心肌梗死，或非致命性大出血），（HR 0.87[0.79-0.95],P=0.004）

　　Antman说：“虽然氯吡格雷是非常有效的抗血小板药物，但是许多服用此药的患者仍发生严重的缺血事件。更高剂量血小板凝集阻滞剂TRITON-TIMI 38研究代表了急性冠脉综合征患者抗血小板治疗的最新进展。”

　　Antman说，还有一些病人服用prasugrel并没有获益，比如卒中史，高龄和低体重者。持续进行的TRITON-TIMI 38亚组研究药物代谢动力学亚组分析将指导改变维持给药剂量。

　　本研究由Daiichi Sankyo Co. Ltd and Eli Lilly & Co支持。

New antiplatelet therapy improves outcomes

ORLANDO, Nov. 4 -The antiplatelet drug prasugrel offered greater benefit than current, standard therapy for patients who have undergone percutaneous coronary intervention (PCI), according to a late-breaking clinical trial presented at the American Heart Association’s Scientific Sessions 2007.

Dual antiplatelet therapy with aspirin plus a prescription antiplatelet drug is standard treatment for helping reduce complications such as heart attacks or clotting in stents in patients with acute coronary syndromes (ACS) who have undergone PCI to open blocked coronary arteries.

TRITON-TIMI 38, a large, international, double-blind phase 3 trial, compared single dosages of prasugrel, a novel antiplatelet drug, and clopidogrel, a commonly used prescription antiplatelet.Both medications are in a class of drugs called thienopyridines.

At these doses, “Prasugrel was been shown to be more potent, work more quickly and have more consistent antiplatelet effects than standard, approved doses of clopidogrel,” said Elliott M. Antman, M.D., professor of medicine at Harvard Medical School and director of the Samuel A. Levine Cardiac Unit at Brigham and Women’s Hospital in Boston, Mass.

TRITON - TIMI 38 enrolled 13,608 patients with moderate to high-risk ACS who were scheduled to undergo PCI.Participants were randomized at 707 sites in 30 countries.  Patients were given either prasugrel (60 mg as a one-time “loading” dose, followed by a daily 10 mg maintenance dose) or clopidogrel (300 mg loading dose and a daily 75 mg maintenance dose) for up to 15 months following PCI.

The primary efficacy endpoint (death from cardiovascular causes, heart attack or stoke) was significantly lower on prasugrel (12.1 percent of patients randomized to clopidogrel and 9.9 percent of patients randomized to prasugrel (HR 0.81[0.73-0.90], P=0.0004)), meeting the primary hypothesis of superiority.  This dose of prasugrel was also associated with a significantly lower incidence of stent thrombosis (HR 0.48[0.36-0.64], P<0.0001), urgent target vessel revascularization (HR 0.66 [0.54-.081], P<0.0001) and heart attacks (HR 0.76 [0.67-.085], P<0.0001).  While major bleeding was also significantly higher with prasugrel (2.4 percent of patients versus 1.8 percent of patients randomized to clopidogrel (HR 1.32 [1.03-1.68], P=0.03), the balance of efficacy and safety, net clinical benefit (all cause mortality, nonfatal MI, nonfatal stroke, or nonfatal major bleed), favored prasugrel (HR 0.87 [0.79-0.95], P=0.004).

“Although clopidogrel is a highly effective antiplatelet drug, many patients who receive it still have serious ischemic events despite reliably taking the drug,” said Antman.“The benefits of the higher degrees of inhibition of platelet aggregation achieved with the doses of prasugrel that we tested in TRITON-TIMI 38 represent the latest advance in antiplatelet therapy for patients with an acute coronary syndrome.”

Antman said there were some patients who did not do as well with this dosage of prasugrel, such as those who had a history of prior stroke, were elderly and had a low body weight,Potential modifications of the maintenance dose will be guided by ongoing analyses of a pharmacokinetic substudy in TRITON-TIMI 38.

Support for this study was provided by Daiichi Sankyo Co. Ltd and Eli Lilly & Co.