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.

ST段抬高型心肌梗死患者行直接经皮冠状动脉介入术前依替巴肽的急诊早期使用:TITAN(急性心肌梗死患者中至应用依替巴肽治疗时间)-TIMI34试验的结果

背景:ST段抬高型心肌梗死(STEMI)患者行直接经皮冠状动脉介入(PCI)术前心外膜血流的早期恢复常伴有较好的临床预后。方法:设想,与在心脏导管室(CCL)行诊断性血管造影后使用血小板糖蛋白IIb/IIIa受体拮抗剂依替巴肽相比较,行PCI术前在急诊科(ED)早期使用依替巴肽可获得更好的心外膜血流和心肌灌注。343例STEMI患者被随机分为两组,分别于ED早期(n=180)或CCL(n=163)应用依替巴肽。

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.

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.

阿司匹林和溶栓疗法加用氯吡格雷治疗ST段抬高心肌梗死

BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel(300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin(dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery(defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy(95 percent confidence interval, 24 to 47 percent; P< 0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent(from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.

Angiographic and clinical outcomes in elderly subjects treated with percutaneous coronary intervention following fibrinolytic administration for ST-elevation myocardial infarction

Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) patients. The association of patient age with angiographic characteristics of flow and perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) following the administration of fibrinolytic therapy has not been previously investigated. Objectives and Methods We examined the association between age (≥ 70 years or ＜ 70years)and clinical and angiographic outcomes in 1472 STEMI patients who underwent rescue/adjunctive PCI following fibrinolytic therapy in 7 TIMI trials. We hypothesized that elderly patients would have slower post-PCI epicardial flow and worsened outcomes compared to younger patients. Results The 218 patients aged ≥ 70 years (14.8%) had more comorbidities than younger patients. Although these patients had significant angiographic improvement in TIMI frame counts and rates of TIMI Grade 3 flow following rescue/adjunctive PCI, elderly patients had higher (slower)post-PCI TIMI frame counts compared to the younger cohort (25 vs 22 frames, P = 0.039), and less often achieved post-PCI TIMI Grade 3 flow (80.1 vs 86.4%, P = 0.017). The association between age ( ≥70 years) and slower post-PCI flow was independent of gender, time to treatment, left anterior descending (LAD) lesion location, and pulse and blood pressure on admission. Elderly patients also had 4-fold higher mortality at 30 days (12.0 vs 2.7%,P = 0. 001 ). Conclusions This study suggests one possible mechanism underlying worsened outcomes among elderly STEMI patients insofar as advanced chronological age was associated with higher TIMI frame counts and less frequent TIMI Grade 3 flow after rescue/adjunctive PCI.

比较应用裸金属支架与药物洗脱支架行经皮冠状动脉介入治疗非ST段抬高型急性冠状动脉综合征对生物标记物水平的影响

Drug-eluting stents(DESs) deliver biphasic(early and late)-elution of anti-inflammatory compounds. We therefore hypothesized that DESs would be associated with early reductions in inflammatory biomarker release after percutaneous coronary intervention(PCI). A total of 741 patients with non-ST-elevation acute coronary syndrome underwent PCI in the Randomized Trial to Evaluate the Relative PROTECTion against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia among Anti-Platelet and Anti-Thrombotic Agents(PROTECT) Thrombolysis In Myocardial Infarction 30 study of eptifibatide and reduced-dose antithrombin compared with bivalirudin. Serial biomarkers C-reactive protein, troponin, creatine kinase-MB, soluble CD40 ligand, interleukin-6, prothrombin fragment F1.2, and RANTES(regulated on activation, normal T-cell expressed and secreted) were assessed through 24 hours after PCI. DES use was at the investigator’s discretion. Patients treated with DESs(n=665) versus bare metal stents(n=139) were more likely to have patent arteries before PCI(92.0%vs 86.6%, p=0.04), Thrombolysis In Myocardial Infarction myocardial perfusion grade 3(57.9%vs 47.7%, p=0.033), and the left anterior descending artery as the culprit artery(38.5%vs 18.3%, p< 0.001). The increase in C-reactive protein and troponin was lower among patients undergoing DES implantation(median 2.1 vs 3.5 mg/L for C-reactive protein, median 0.11 vs 0.41 ng/ml for troponin), even after adjustment for randomized treatment, clopidogrel before treatment, diabetes mellitus status, epicardial patency, left anterior descending artery location, and myocardial perfusion(p=0.036 and p=0.039, respectively). Interleukin-6 was lower with DESs on univariate analysis but not multivariate analysis. Creatine kinase-MB, soluble sCD40 ligand, prothrombin fragment F1.2, and RANTES did not differ by DES use. In conclusion, patients undergoing DES implantation achieved more reductions in periprocedural markers of inflammation and necrosis than patients receiving bare metal stents among those with non-ST-elevation acute coronary syndrome.

IDEAL的胆固醇水平更低更好

三十年前，JAMA杂志发表了多危险因素干预试验（Primau Results of the Multiple Risk Factor Itervention Trial，MRFIT）。该试验试图证实降低胆固醇以及治疗其他危险因素，可减少心血管的发病率和死亡率。以后，多个试验均显示了降低胆固醇的心血管获益，特别是低密度脂蛋白胆固醇（low—density lipoprotein cholesterol，LDL—C）。然而，直到1993年，并无试验明确证实总死亡率降低。所以，关于降低胆固醇是否能真正获益仍存在争议。。

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.