心肌梗死后使用噻氯匹定与阿司匹林的对比研究（摘要）

疾病急性心肌梗死目的比较经溶栓治疗急性心肌梗死存活者噻氯匹定与阿司匹林的疗效。研究设计双盲、随机、多中心试验随访6个月病人1470例急性心肌梗死接受溶栓治疗存活的住院病人治疗方案噻氯匹定(250mg片剂;734例)或普通     

Stenting versus thrombolysis in acute myocardial infarction trial (STAT)

OBJECTIVES: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.     

Ticlopidine alone versus ticlopidine plus aspirin for preventing recurrent stroke

OBJECTIVE: To compare the efficacy and safety of two antiplatelet regimens, ticlopidine alone (200 mg daily) and ticlopidine (100 mg daily) plus aspirin (81 mg daily), in patients with ischemic stroke from the Tokai district of Japan. METHODS: A randomized comparative study was performed from April 1992 until December 1995, with follow-up for an average of 1.59 years (maximum: 3 years). Statistical analysis was done on 270 eligible patients (138 treated with ticlopidine alone and 132 treated with ticlopidine plus aspirin). PATIENTS: A total of 276 patients who had cerebral infarction within the previous 1 to 6 months, or one or more transient ischemic attacks within the previous 3 months. RESULTS: The incidence of ischemic and hemorrhagic stroke, myocardial infarction, and other vascular events was 10.1% (n = 14) in the ticlopidine group and 9.8% (n = 13) in the ticlopidine plus aspirin group, showing no significant difference (p = 0.933). There was also no significant difference in the event-free rate between the two groups (p = 0.5003, Kaplan-Meier analysis and log-rank test). Regarding serious adverse reactions, neutropenia occurred in one patient from the ticlopidine group, while gastric ulcer and thrombocytopenia occurred in one patient each from the ticlopidine plus aspirin group. CONCLUSION: We conclude that both antiplatelet regimens are comparable in efficacy and safety for preventing the recurrence of ischemic stroke.     

Efficacy of acebutolol after acute myocardial infarction (the APSI trial)

A randomized, placebo-controlled trial was carried out to determine the effectiveness of acebutolol in preventing late death in high-risk patients surviving an acute myocardial infarction (MI). The average 1-year mortality rate in placebo groups of 9 trials of β blockers in post-MI patients was 7.2% compared with 17% in a nonselected cohort of patients who had survived at least 7 days after an MI. The mandate for this trial was based on the fact that high-risk patients whose mortality rate exceeds 20% have not been enrolled in significant numbers in previous trials. It remains to be proved whether β-blocking therapy in this patient population is beneficial. Selection of high-risk patients for inclusion in the trial was based on an algorithm set up from the Essai de Prevention Secondaire de l'Infarctus du Myocarde Registry. At the time of the second interim analysis, the mortality rate in the placebo group was 12%, lower than expected (≥20%). The trial was stopped; at that time, 309 patients had been allocated to placebo and 298 patients to acebutolol therapy. After 318 days, there were 17 deaths in the acebutolol-treated group and 34 in the placebo group, a reduction in total mortality of 48% (p = 0.019). There were 30 vascular deaths in the placebo group and 12 in the acebutolol group. Thus, cardiovascular mortality with acebutolol was reduced by 58% (p = 0.006). The incidence of all cardiovascular-related deaths was lower in the acebutolol-treated group. The total reduction in mortality did not appear to be correlated with secondary risk factors. Although the objective of the study, which was to enroll patients at high risk, was not met, the patients in this trial were at higher risk than average patients in previous trials. We conclude that moderately high-risk post-MI patients can benefit from treatment with β blockers, and β blockers with mild intrinsic sympathomimetic activity can be effective.     

Regional myocardial blood flow in experimental myocardial infarction after pretreatment with aspirin

The effects of aspirin on myocardial blood flow in an area of ischemia were studied in 12 baboons. In each, a diagonal branch of the left anterior descending coronary artery was ligated. Six of the baboons received aspirin (2 X 600 mg orally, 12 hours and 1 hour before ligation); the other six did not receive aspirin and served as a control group. The extent of myocardial ischemia was delineated with an electrode wire grid on the surface of the anterior left ventricular wall. The maximal area circumscribed by electrodes with 2 mV or more ST segment elevation was compared with the area of reduced myocardial blood flow. Myocardial blood flow was measured with the radioactive microspheres method using strontium-85-labeled carbonized spheres. Two areas of reduced myocardial blood flow were noted, one with severely reduced flow in the center of the myocardial infarct (0 to 49% of noninfarcted myocardium) and another with mild to moderately reduced myocardial blood flow at the border of the myocardial infarct (50 to 90% of noninfarcted myocardium). Myocardial blood flow in the border area (margins of ST elevation area) for the total wall was 85 +/- 8% of normal in the aspirin-treated animals and 40 +/- 4% in the control group (p less than 0.01); for the epicardium it was 67 +/- 10% of normal in noninfarcted myocardium after aspirin and 37 +/- 5% for the control group (p less than 0.05); and for the endocardium it was 78 +/- 8% of normal in noninfarcted myocardium after aspirin and 39 +/- 6% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ticlopidine and aspirin interactions.

The risk-benefit balance when aspirin is compared with aspirin combined with ticlopidine is being investigated in several multicentre trials (MUSIC and WEST II versus TASTE, MUST, and STARS respectively). Cardiologists follow one of two strategies. Some prefer a more aggressive antiplatelet regimen, disregarding the risk of neutropenia (0.7%) because they want to avoid lessening the therapeutic effect of vessel patency obtained with stent implantation. Others give only aspirin (a money saving approach) confident that IVUS inspection (an expensive approach) will allow an adequate evaluation of full stent expansion and lesion coverage, despite a more pronounced activation of the coagulation cascade. Our impression so far is that the combination of ticlopidine and aspirin has a more favourable risk-effect balance.     

High dose aspirin and left ventricular remodeling after myocardial infarction

Background Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. Methods and results Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 ± 1.7 vs. placebo MI 15.9 ± 2.5 mm²), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 ± 1.3 mm², p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1β were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. Conclusion Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.     

Randomized comparative trial of triflusal and aspirin following acute myocardial infarction.

AIMS: To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction. METHODS AND RESULTS: In this double-blind, multicentre, sequential design study, patients were randomized within 24 h of acute myocardial infarction symptom onset to receive triflusal 600 mg or aspirin 300 mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0.882 [0.634-1.227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0.364 [0.146-0.908]; P = 0.030). There was no significant difference between treatments for death (OR [95% CI]: 0.816 [0.564-1.179]; P = 0.278), non-fatal reinfarction (OR [95% CI]: 1.577 [0.873-2.848]; P = 0.131) or revascularization (OR [95% CI]: 0.864 [0.644-1.161]; P = 0.334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033). CONCLUSION:Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.     

Urokinase plus heparin versus aspirin in unstable angina and non-Q-wave myocardial infarction

The pivotal role of thrombosis in unstable angina and non-Q-wave myocardial infarction has been established recently. To assess the value and safety of thrombolytic therapy compared to conventional antithrombotic therapy (aspirin) in arresting progression in this setting to recurrent ischemic end-points, 25 patients presenting with unstable angina and an electrocardiogram showing subendocardial ischemia were randomized to receive either aspirin 325 mg daily, or urokinase 3 x 10(6) U intravenously, over 30 minutes followed by heparin. Incidence of endpoints (intractable ischemia requiring mechanical intervention, new myocardial infarction or death) was determined over 7 days. Coronary arteriography was performed at 24 to 72 hours to determine extent of coronary artery disease and morphologic severity of the culprit lesion, graded by a semiquantitative scoring system ranging from 4+ (definite thrombosis) to 0 (chronic lesion). In the first 24 hours, 7 of 13 aspirin versus 1 of 12 urokinase patients exhibited ischemia progression (p less than 0.05). By 7 days, progression to a primary ischemic endpoint occurred in 8 of 13 aspirin patients (3 myocardial infarctions and 5 intractable ischemias) versus 3 of 12 urokinase patients (2 intractable ischemias and 1 death) (p = 0.18). The apparent benefit of urokinase followed by heparin compared to conventional aspirin therapy in arresting early progression of unstable angina or non-Q-wave myocardial infarction was not associated with enhanced culprit lesion morphology (mean lesion severity score 2.7 +/- 1.5 vs 2.8 +/- 1.6 in aspirin-treated patients). Large scale, randomized trials to assess the clinical utility of urokinase for unstable angina are warranted.     

Warfarin and aspirin versus aspirin alone in patients with acute myocardial infarction: a pilot study

The benefits of anticoagulant therapy and antiplatelet agents in secondary prevention of myocardial infarction (MI) are well known. Administration of combined warfarin and aspirin (ASA) has not been well studied. The objective of this study was to compare the effect of coadministration of warfarin and ASA with administration of ASA alone on outcome of patients after MI. One hundred forty age- and sex-matched survivors of MI were randomized to receive either 100 mg/day ASA plus enough warfarin to reach a target: international normalized ratio of 2.5 (range: 2-3) (group A, n = 70), or only 100 mg/day ASA (group B, n = 70). The patients were examined for several variables including development of hemorrhage, reinfarction, and rehospitalization for 1 year post MI. Of the variables studied, minor hemorrhagic episodes were observed significantly (p = 0.002) more in group A than in group B patients. Rehospitalization and reinfarction rates, although occurring with lower frequencies in group A than in group B, did not reach the statistical significance level. In postmyocardial infarction patients, warfarin plus ASA did not provide a clinical benefit beyond that achievable with aspirin monotherapy, and for the observed markedly higher incidence of minor hemorrhage in combination therapy, antiplatelet therapy alone seems to be a more reasonable approach.     

西拉普利和阿司匹林对实验性大鼠心肌梗死后心脏间质胶原代谢的影响

目的:观察西拉普利和阿司匹林对实验性大鼠心肌梗死(MI)后心脏间质胶原代谢的影响。方法:采用结扎冠状动脉(冠脉)左前降支的方法建立大鼠MI模型,设立假手术组、梗死组、西拉普利组、阿司匹林组、联合组。术后2周测定循环中血管紧张素Ⅱ(AngⅡ)、6酮PGF1α(6ketoPGF1α)、内皮素1(ET1)水平和心脏梗死区、左室非梗死区及右室的间质胶原含量。结果:各实验组与假手术组比较,血循环中AngⅡ、ET1升高,6ketoPGF1α降低,左室非梗死区及右室的胶原含量明显升高。各实验组间梗死区的胶原含量相互比较差异无统计学意义。与梗死组比较,阿司匹林组血6ketoPGF1α显著降低,左室非梗死区及右室的胶原含量差异无统计学意义;西拉普利组、联合组血AngⅡ、ET1明显降低,6ketoPGF1α显著升高,左室非梗死区及右室的胶原含量明显降低。联合组与西拉普利组比较,6ketoPGF1α显著降低,而左室非梗死区及右室的胶原含量差异无统计学意义。结论:MI后神经内分泌系统过度激活,循环中AngⅡ、ET1明显升高并导致心脏间质胶原含量的升高。西拉普利通过抑制循环紧素血管紧张素醛固酮系统和内皮素系统,降低AngⅡ和ET1,并通过抑制缓激肽降解,抑制心脏非梗死区间质胶原的过度沉积。阿司匹林对MI后心脏间质胶原的沉积无明显影响。西拉普利与阿司匹林联合应用不影响西拉普利的抑制非梗死区心脏间质胶原过度沉积的作用。     

Cost of strategies after myocardial infarction (COSTAMI): a multicentre, international, randomized trial for cost-effective discharge after uncomplicated myocardial infarction.

AIMS: Risk stratification after uncomplicated acute myocardial infarction is mostly applied by either symptom-limited post discharge exercise electrocardiography or pre-discharge submaximal exercise test. Aim of the present study was to determine if early pharmacological stress echocardiography and discharge within 24 hours of the test in cases without induced myocardial ischemia leads to lower costs and similar clinical outcome during 1 year follow up when compared to clinical evaluation and exercise electrocardiography after discharge. METHODS AND RESULTS: Four-hundred fifty-eight patients from 10 participating centers with a recent uncomplicated myocardial infarction were randomized to pharmacological stress echocardiography on day 3-5 followed by early discharge in the case of negative test result (early discharge strategy) (n=233) or clinical evaluation with hospital discharge on day 7-9 and symptom-limited post-discharge exercise electrocardiography at 2-4 weeks after myocardial infarction (usual care strategy) (n=225). At 1 year follow up there were 63 events (4 deaths, 9 non fatal reinfarctions, 50 chest pains requiring hospitalization) in patients randomized to early discharge, and 69 events (6 deaths, 13 reinfarctions, 50 chest pains requiring hospitalization) in usual care (p=ns). Total median individual costs calculated on the basis of hospitalizations, investigations and interventions during 1 year follow up were 3561 for early discharge strategy vs 3850 for usual care strategy (p<0.05). CONCLUSIONS: Early pharmacological stress echocardiography followed by early discharge in case of negative test result gives similar clinical outcome and lower costs after uncomplicated myocardial infarction than clinical evaluation and delayed post-discharge symptom-limited exercise electrocardiography.     

A randomized pilot trial of brief versus prolonged heparin after successful reperfusion in acute myocardial infarction

Controversy exists as to whether and how long heparin treatment is necessary after infarct vessel recanalization. To determine the role of heparin, patients with suitable angiographic features after reperfusion therapy were randomly allocated to receive a brief infusion of intravenous heparin for less than or equal to 24 hours (group 1), adjusted to a partial thromboplastin time of 2 times control or a prolonged infusion for greater than or equal to 72 hours (group 2), using the same titration mechanism. Patients were excluded for complex intimal dissections, large residual filling defects, less than Thrombolysis in Myocardial Infarction grade 3 flow pattern or greater than 50% residual stenosis. Heparin was sustained except for discontinuation 2 to 4 hours before periaccess sheath removal, or if significant bleeding (greater than or equal to 2 units blood transfusion) occurred. The primary endpoints were 1-week patency determined by repeat catheterization or recurrent ischemia, or both, and the incidence of bleeding complications. Fifty patients were randomized, 25 in both groups. Baseline variables were similar; 14 group 1 and 15 group 2 patients received thrombolytic treatment; 20 patients in each group had coronary angioplasty. Two documented reocclusions occurred in both groups. Significant bleeding complications occurred in 0 of 25 (0%) group 1 versus 6 of 25 (24%) group 2 patients (p less than 0.05). Thus, in low-risk patients after successful reperfusion, prolonged heparin therapy does not protect against rethrombosis and is associated with a significantly higher rate of bleeding complications. Therefore, prolonged heparin therapy for greater than 24 hours does not appear to be justified in low-risk patients with successful reperfusion.     

Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: Insights from the coronary angioplasty versus excisional atherectomy trial (CAVEAT)

Objectives. We examined the results of the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) to determine the characteristics and consequences of creatine kinase (CK) and creatine kinase, MB myocardial isoenzyme fraction (CK-MB) elevations after percutaneous coronary intervention.

Background. Enzyme elevations after interventional procedures have usually been thought to be without long-term clinical consequences. However, recent preliminary reports have suggested that there are important long-term clinical sequelae in patients with even mild enzyme elevations after coronary procedures.

Methods. Patients with new native lesions undergoing coronary intervention at 35 clinical sites were randomized to undergo percutaneous coronary angioplasty (n = 500) or directional coronary atherectomy (n = 512). Cardiac enzyme levels were measured 12 and 24 h after the interventional procedure and when clinically indicated for recurrent myocardial ischemia. Enzyme profiles were analyzed using a ratio that compared the peak enzyme level and the local laboratory upper limit of normal. Standard 12-lead electrocardiograms (ECGs) recorded before and after the procedure were interpreted by two independent readers who had no knowledge of the randomization data. Postprocedural myocardial infarction was defined as the appearance of new Q waves on the ECG, CK-MB levels three or more times the upper limit of normal or a total CK concentration two or more times the upper limit of normal when CK-MB levels were unavailable. Regression models were used to evaluate the predictive significance of a postintervention myocardial infarction with respect to clinical outcomes at 30 days and 1 year.

Results. There were 78 myocardial infarctions in the atherectomy group and 34 in the angioplasty group (15.2% vs 6.8%, p = 0.001). Patients with a myocardial infarction more often had a repeat intervention or emergency coronary artery bypass surgery. Hospital length of stay was increased among patients with an infarction, as were mean hospital costs ($17,340.65 vs $11,308.47, p = 0.0003). Postprocedural myocardial infarction was highly predictive of mortality, bypass surgery or repeat intervention within 30 days (p < 0.0001).

Conclusions. Myocardial infarction occurred commonly after coronary intervention in CAVEAT and was associated with a worse clinical outcome. Although the incidence of myocardial infarction was higher with atherectomy than with angioplasty, the baseline characteristics and consequences of the infarctions were similar between the treatments with regard to 30-day outcome. Myocardial enzyme elevations after an otherwise successful interventional procedure may identify a population at risk for a future cardiac event.     

French multicenter trial of anistreplase versus heparin in acute myocardial infarction

Summary Eighty-four patients aged less than 71 years with less than 4-hour duration acute myocardial infarction (AMI) were randomized in a multicenter study to 30 U anistreplase or heparin (single injection of 6500 IU followed by 1000 IU/hr). Early reperfusion was assessed from ECG changes (50% of sum ST decrease 2 hours postdosing) and the CK release profile (CK peak <16 hours after onset of symptoms, CK slope >10%hr). Reperfusion rates in patients meeting at least two criteria of reperfusion were 62.5% on anistreplase versus 27.5% on heparin. On delayed angiogram (13.7±3.4 days), patency rates were 66% with anistreplase versus 47% (NS) with heparin in 76 patients. Global LVF was similar in both groups. With anistreplase, the mean lowest fibrinogen level was 0.43±0.55 g/l, plasminogen was 20±9%, and the highest F.D.P. was 1447±548 g/ml. All values recovered by hour 48. In-hospital and 1-year follow-up mortality was 7.2% (three patients) with anistreplase versus 10.2% (four patients) with heparin. Bleeding occurred in 9.7% and 5.1% of the patients (NS), respectively. No intracranial hemorrhage occurred. Thus, with combined clinical criteria or reperfusion, anistreplase is twice as efficient as heparin, has a good tolerance, and is easy to use as a single injection. Anistreplase is the generic name ofEminase, a registered trademark of Beecham Pharmaceuticals.This paper was presented, in part, at the 3rd Cardiovascular Pharmacotherapy International Symposium, October 15–19, 1989, Kyoto, Japan.