新蝶呤的长期预后价值:急性冠状动脉综合征患者单核细胞激活的一种新标记物

背景:单核细胞激活被认为在急性冠状动脉综合征(ACS)的发病过程中起着重要作用。新蝶呤是单核细胞激活的一种可溶性标记物,其水平升高对稳定性冠状动脉疾病具有预后预测价值。

依诺肝素与普通肝素在ST段抬高心肌梗死接受溶栓患者抗凝血酶治疗中的应用:ExTRACT-TIMI25试验

ExTRACT- TIMI 25 is a randomized, double- blind, double- dummy, parallel group, multinational, clinical trial designed to provide definitive data on the efficacy and safety of a strategy of enoxaparin throughout index hospitalization vs standard treatment with UFH as adjunctive antithrombin therapy in patients with STEMI who are eligible for fibrinolysis. If the dose reduction of enoxaparin in elderly patients and more conservative use of UFH than has been the case in prior trials of fibrinolysis are both associated with lower rates of bleeding as compared with historical data, a means for improving the safety of pharmacological reperfusion will be established.

新型抗缺血药物治疗急性冠状动脉综合征的评价:雷诺嗪用于减少非ST段抬高型急性冠状动脉综合征局部缺血的代谢效能(MERLIN)-TIMI36试验的试验设计与原理

Background: Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes(NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. Study Design: MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy(N=6500). Eligible patients are randomized 1 ∶1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion(40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Holter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of longterm safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 310 deaths are recorded with expected completion in 24 to 28 months. Conclusions: MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS.

依诺肝素与普通肝素在联合纤溶疗法治疗ST段抬高型心肌梗死中作用的比较

BACKGROUND: Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. METHODS: We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. RESULTS: The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group(17 percent reduction in relative risk, P< 0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving enoxaparin(33 percent reduction in relative risk, P< 0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given enoxaparin(P=0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given enoxaparin(P< 0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively(P< 0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage(a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given enoxaparin(P< 0.001). CONCLUSIONS: In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit.

氯吡格雷在ST段抬高型心肌梗死溶栓后早期和持续动脉开放中的作用:ECG CLARITY-TIMI28研究

Objectives: This study was designed to determine the relationship between clopidogrel and early ST-segment resolution(STRes) and the interaction of the two with clinical outcomes after fibrinolysis. Background: ST-segment resolution is an early noninvasive marker of coronary reperfusion. Methods: The CLARITY-TIMI 28(Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28) trial randomized 3,491 patients with ST-segment elevation myocardial infarction(STEMI) undergoing fibrinolysis to clopidogrel versus placebo. ST-segment resolution was defined as complete(>70%), partial(30%to 70%), or none(< 30%). Results: Electrocardiograms were valid for interpretation in 2,431 patients at 90 min and 2,087 at 180 min. There was no difference in the rate of complete STRes between the clopidogrel and placebo groups at 90 min(38.4%vs. 36.6%at 90 min). When patients were stratified by STRes category, treatment with clopidogrel resulted in greater benefit among those with evidence of early STRes, with greater odds of an open artery at late angiography in patients with partial(odds ratio[OR] 1.4, p=0.04) or complete(OR 2.0, p< 0.001) STRes, but no improvement in those with no STRes at 90 min(OR 0.89, p=0.48)(p for interaction=0.003). Clopidogrel was also associated with a significant reduction in the odds of an in-hospital death or myocardial infarction in patients who achieved partial(OR 0.30, p=0.003) or complete STRes at 90 min(OR 0.49, p=0.056), whereas clinical benefit was not apparent in patients who had no STRes(OR 0.98, p=0.95)(p for interaction=0.027). By 30 days, the clinical benefit of clopidogrel was predominately seen in patients with complete STRes. Conclusions: Clopidogrel appears to improve late coronary patency and clinical outcomes by preventing reocclusion of open arteries rather than by facilitating early reperfusion.