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.

非ST段抬高的急性冠脉综合征患者肾小球滤过率与随后死亡率的关系:来自5个心肌缺血溶栓治疗临床试验的13307例患者的观察结果

To determine the association of glomerular filtration rate (GFR) with clinical outcomes in the setting of non-ST-segment elevation acute coronary syndromes(NSTE-ACS). Data were pooled from five NSTE-ACS TIMI trials(TIMI 11A and B, TIMI 12, OPUS-TIMI 16 and TACTICS-TIMI 18) and were available in 13 307 patients. GFR was assessed as a continuous and a categorical variable(normal: ≥90 mL/min/1.73 m2,n=4952; mildly decreased: 60-89 mL/min/1.73 m2, n=6262; and moderately to severely decreased GFR: < 60 mL/min/1.73 m2, n=2093). There was an independent association between decreasing GFR and mortality at 30 days (OR 1.19, 95%CI 1.12-1.27, p< 0.001) and at 6 months (OR 1.16, 95%CI 1.11-1.22, p< 0.001). The combination of TIMI risk score(TRS) and decreasing GFR provided further mortality risk stratification with highest 30-day and 6-month mortality rates among patients with the lowest GFR who also had a TRS ≥5(9.1%and 15.4%, respectively). Decreasing GFR was also independently associated with stroke and recurrent ischaemia at 30-days as well as with major bleeding (p< 0.001). In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS.

氯吡格雷作为心肌梗死溶栓疗法辅助再灌注治疗措施(CLARITY-TIMI)-28试验的设计和原理

Background: Although fibrinolysis is effective in improving outcomes in ST- elevation myocardial infarction(STEMI), failure to achieve reperfusion and/or reocclusion of the infarct- related artery occur in substantial proportions of patients during their index hospitalization and are associated with a significant increase in mortality. We hypothesize that the addition of clopidogrel to standard fibrinolytic therapy in patients with acute STEMI will improve reperfusion. Study design: CLARITY- TIMI 28 is a multicenter, international, randomized, double- blind, placebo- contro- lled trial designed to examine the efficacy and safety of clopidogrel when added to standard adjuvant therapy for fibrinolysis. The primary efficacy end point is the composite of an occluded infarct- related artery(defined as TIMI flow grade 0 or 1) on the predischarge angiogram or death or a recurrent myocardial infarction(MI) up to the start of coronary angiography. For subjects who do not undergo angiography, occurrence of death or recurrent MI by day 8 or by hospital discharge, whichever comes first, is used. The primary safety assessment is TIMI major bleeding. Secondary end points include ST resolution at 180 minutes and the clinical composite of death, MI, or recurrent ischemia. Substudies include analyses of biomarkers, DNA, continuous electrocardiogram monitoring, and initiation of treatment in the ambulance. Conclusions: CLARITY- TIMI 28 will help to define the role of clopidogrel as part of the pharmacologic reperfusion regimen for acute STEMI.

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.

碘造影剂注射对ST段抬高型心肌梗死患者冠状动脉狭窄百分数的影响以及此影响对于冠状动脉内药物治疗试验的意义

冠状动脉内应用纤溶、抗血小板和抗血栓药物可溶解血凝块,但尚未研究注射本身的机械力对消除血凝块的可能作用。TITAN-TIMI34研究中,在急诊室(ER)接受普通肝素和阿司匹林预治疗的ST段抬高型心肌梗死患者被随机分配在ER接受依替巴肽治疗(n=131)

在不稳定性心绞痛或非ST段抬高性心肌梗死的进展期间运动负荷试验的安全性

Patients(n=1,106) were chosen from the conservative arm of the Treat Angina with aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction(TACTICS-TIMI) 18 trial. Only 1 patient had a myocardial infarction and another died on the day of stress testing(mortality 0.12%). In patients with unstable angina pectoris or non-ST-eleva-tion myocardial infarction treated with aspirin, heparin, and tirofiban, performance of an exercise or a pharmacologic stress test in selected patients within 48 to 72 hours after admission appears to be associated with a low risk of complications.