Fibrinolysis For ST-elevation Myocardial Infarction Research Articles

Diagnostic accuracy of reperfusion criteria following fibrinolysis for ST-elevation myocardial infarction

Diagnostic accuracy of reperfusion criteria following fibrinolysis for ST-elevation myocardial infarction

TCTAP A-070 Outcomes of Ticagrelor Administration During Fibrinolysis for ST-Elevation Myocardial Infarction

TCTAP A-070 Outcomes of Ticagrelor Administration During Fibrinolysis for ST-Elevation Myocardial Infarction

Two Years Door-to-Balloon Times for ST-segment Elevation Myocardial Infarction in a New Regional 24/7 Primary Percutaneous Coronary Intervention Centre

Primary percutaneous coronary intervention (PPCI) results in superior outcomes compared to fibrinolysis in ST-elevation myocardial infarction (STEMI) when delivered in a timely manner. A key performance metric of a PPCI service is providing door-to-balloon times (D2BT) in under 90 min. Shorter D2BT is associated with reduction in cardiac mortality and morbidity.

Outcomes of Ticagrelor Use Following Fibrinolysis for ST-Elevation Myocardial Infarction

Fibrinolysis with concurrent aspirin and clopidogrel is employed for the treatment of ST-elevation myocardial infarction (STEMI) in patients who cannot access timely primary percutaneous coronary intervention (PCI). The utility of more potent P2Y12 inhibitors such as ticagrelor in the setting of fibrinolysis remains uncertain. This study sought to investigate the safety and efficacy of up-front ticagrelor loading in patients treated with fibrinolysis for STEMI.

Long-term differences in clot formation and endothelial function between STEMI patients with occlusion of infarct-related artery and those with spontaneous reperfusion

Abstract Introduction Enhanced activation of endogenous fibrinolysis in ST-elevation myocardial infarction (STEMI) patients is the main cause of spontaneous reperfusion of the infarct-related artery (IRA) in the acute period. Whether this enhanced activation remains in the deferred period of myocardial infarction remains unclear. Purpose The main purpose of our work was to analyze the process of clot formation and endogenous fibrinolysis in patients with a history of myocardial infarction. Methods We included 51 patients with a history of myocardial infarction (median, 35 months). Of these patients, 19 had a spontaneous reperfusion of the IRA (SR group) during the index event, and 32 had a total occlusion of the IRA (occlusion group). We assessed parameters of clot formation and endogenous fibrinolysis using thromboelastometry and a thrombodynamics assay. We analyzed endothelial function using the flow-mediated dilation test (FMD). Results The process of clot formation was more active in the occlusion group than in the SR group. Thus, the initial, mean, and total clot velocity times were significantly higher in the occlusion group than in the SR group: 57.2 mcm/min vs. 60.25 mcm/min; 28,1 mcm/min vs. 31.9 mcm/min; and 28.7 mcm/min vs. 31.9 mcm/min, respectively; p<0.01. The clot size was much bigger in the occlusion group than in the SR group (1,190.5 mcm vs. 1,315 mcm; p<0.01). No differences in endogenous fibrinolysis parameters were observed between the two groups. Endothelium function was better in the SR-group than in the occlusion group (FMD 17.4% vs 11.3%, p<0.01). Conclusion STEMI patients with occlusion of the IRA and those with spontaneous reperfusion remain different in clot formation and endothelial function even after many years. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Russian Science Foundation grant

Effect of remote ischaemic conditioning on platelet reactivity and endogenous fibrinolysis in ST-elevation myocardial infarction: a substudy of the CONDI-2/ERIC-PPCI randomized controlled trial.

Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal models of myocardial infarction. Platelet thrombus formation is a critical determinant of outcome in ST-segment elevation myocardial infarction (STEMI). Whether the beneficial effects of RIC are related to thrombotic parameters is unclear. In a substudy of the Effect of Remote Ischaemic Conditioning on clinical outcomes in STEMI patients undergoing Primary Percutaneous Coronary Intervention (ERIC-PPCI) trial, we assessed the effect of RIC on thrombotic status. Patients presenting with STEMI were randomized to immediate RIC consisting of an automated autoRIC™ cuff on the upper arm inflated to 200 mmHg for 5 min and deflated for 5 min for four cycles (n = 53) or sham (n = 47). Venous blood was tested at presentation, discharge (48 h) and 6-8 weeks, to assess platelet reactivity, coagulation, and endogenous fibrinolysis using the Global Thrombosis Test and thromboelastography. Baseline thrombotic status was similar in the two groups. At discharge, there was some evidence that the time to in vitro thrombotic occlusion under high shear stress was longer with RIC compared to sham (454 ± 105 s vs. 403 ± 105 s; mean difference 50.1 s; 95% confidence interval 93.7-6.4, P = 0.025), but this was no longer apparent at 6-8 weeks. There was no difference in clot formation or endogenous fibrinolysis between the study arms at any time point. RIC may reduce platelet reactivity in the first 48 h post-STEMI. Further research is needed to delineate mechanisms through which RIC may reduce platelet reactivity, and whether it may improve outcomes in patients with persistent high on-treatment platelet reactivity.

In the transition from fibrinolysis to primary PCI, the HERO trials help refine STEMI ECG interpretation and Q wave analysis potentially alters future management.

Electrocardiogram sub-studies from the Hirulog Early Reperfusion/Occlusion 1 and 2 trials, which tested bivalirudin as an adjunctive anticoagulant to fibrinolysis in ST-elevation myocardial infarction, have contributed to the literature. The concept of using the presence of infarct lead Q waves to determine reperfusion benefit has subsequently been explored in multiple primary percutaneous coronary intervention studies. The angiographic findings before percutaneous coronary intervention combine with the baseline electrocardiogram to accurately diagnose ST-elevation myocardial infarction and evaluate its potential territory. This review discusses the relative merits of the presence of infarct lead Q waves versus time duration from symptom onset using observational data from cohorts of patients from multiple clinical trials. The presence of infarct lead Q waves at presentation has been repeatedly shown to be superior to time duration from symptom onset in determining prognosis, despite that continuous variable (time duration) statistically should be more powerful than dichotomous variable (Q wave). If quantitative or semi-quantitative measurement of Q waves correlates well with irreversible myocardial injury in vivo (a research goal of many cardiac magnetic resonance imaging studies), Q waves measurements by mirroring ST-elevation myocardial infarction evolution better than the current metric of time duration of symptoms will impact future ST-elevation myocardial infarction reperfusion management. Newer methodology will more quickly capture and transmit electrocardiogram information including infarct lead Q waves potentially before first medical contact, and help differentiate new evolving Q waves of the ongoing ST-elevation myocardial infarction from old changes. Q waves as the new metric in ST-elevation myocardial infarction reperfusion should be tested in upcoming trials.

Point of Care Tests VerifyNow P2Y12 and INNOVANCE PFA P2Y Compared to Light Transmittance Aggregometry After Fibrinolysis.

Detection of high on-treatment platelet reactivity (HPR) by point-of-care tests has not been validated after successful fibrinolysis for ST-elevation myocardial infarction. We assessed the validity of the point-of-care VerifyNow P2Y12 (VN) and INNOVANCE PFA P2Y (PFA) tests on HPR compared to light transmittance aggregometry (LTA) in these patients. The HPR was identified in 10 (34.5%) patients, 15 (51.7%) patients, and 14 (50%) patients using LTA, VN, and PFA, respectively. Discrepancies were observed between the tests despite significant correlations between platelet reactivity measures by LTA and VN (r = 0.74; P < .0001) and LTA and PFA (r = .75; P < .0001). Compared to LTA, VN and PFA were associated with a 92% and 53% and 92% and 64% positive predictive value (PPV) and negative predictive value (NPV), respectively, in detecting HPR. When combined, VN and PFA results yielded 90% and 100% PPV and NPV values if discrepancies between the 2 tests were considered as non-HPR. The VN or PFA identify patients without HPR correctly but overestimate the proportion of HPR patients. The association of the 2 tests, in case of HPR, improves the accuracy of the detection of HPR.

Does renal function affect the efficacy or safety of a pharmacoinvasive strategy in patients with ST-elevation myocardial infarction? A meta-analysis

The efficacy and safety of pharmacoinvasive strategy following fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to renal function have not been established. Using patient-level data from 4 randomized controlled trials, we examined the efficacy and safety of pharmacoinvasive versus standard treatment after fibrinolysis for STEMI. Patients were stratified based on the estimated glomerular filtration rate (eGFR) on presentation (<60 mL/min/1.73 m2 vs ≥60 mL/min/1.73 m2). The primary outcome was the composite of death or reinfarction at 30 days. Of 2,029 patients, 457 (23%) had an eGFR<60 mL/min/1.73 m2. Patients with eGFR<60 mL/min/1.73 m2 were older and had higher Thrombolysis in Myocardial Infarction risk scores. Compared with patients with eGFR≥60 mL/min/1.73 m2, patients with renal dysfunction had higher rates of the primary outcome (5.3% vs 11.8%, respectively; P<.001). There was no significant heterogeneity in the treatment effect of pharmacoinvasive strategy on the primary outcome (P heterogeneity=.73) or the rate of death or reinfarction at 1 year (P heterogeneity=.64) in relation to eGFR. Patients with renal dysfunction had higher rates of in-hospital major bleeding compared with patients with eGFR ≥60 mL/min/1.73 m2 (7.7% vs 4.3%, respectively; P=.004); however, there was no difference in bleeding events between treatment arms in the overall cohort or in relation to eGFR (P heterogeneity=.67). Renal impairment is associated with increased rates of adverse events in STEMI patients treated with fibrinolysis. However, the safety and efficacy of pharmacoinvasive strategy are preserved in patients with renal impairment on presentation.

What to Do Following Fibrinolysis for ST-Elevation Myocardial Infarction

What to Do Following Fibrinolysis for ST-Elevation Myocardial Infarction

Abstract 162: Evolution of Acute Coronary Syndrome Treatment During Last Years in Russian Hospitals (Based on Results of RECORDs Registries)

Background and Purpose: The prospective registries are the most powerful evaluation tool to characterize patients and features of acute coronary syndrome (ACS) treatment. There have been a lot of changes in ACS treatment in Russian hospitals in recent 5-7 years. The aim of our study was to evaluate changes in the ACS treatment occurred in Russia during the last few years. Methods: We conducted the series of independent registries of ACS which were organized by the initiative of their participants - RECORD registries. The first regi stry was held in 2007 (18 centers in 13 cities, n=796). The RECORD-2 registry was conducted in 2009-2011 (7 centers in 7 cities, n=1656). In this analysis pooled data of the RECORD and RECORD-2 (“old” registries; n=2452) were compared with data of the RECORD-3 (“new” registry), conducted in March-April 2015 (47 centers in 37 cities, n=2370). Results: In comparison with “old” registries significantly more patients from “new” registry were hospitalized in PCI-capability hospitals (72.5% vs 56.7%; p&lt;0.0001). The rate of troponin detection was also higher in “new” registry (75.7% vs 41.5%; p&lt;0.0001). The rate of primary PCI (pPCI) in ST-elevation myocardial infarction (STEMI ) was 39.0% in “new” and 36.3% in “old” registry (p=0.24). The rate of pPCI in PCI-capability centers wasn’t also significantly higher in “new” registry (47.2% vs 45.8%). The rate of fibrinolysis in STEMI was nearly similar (32.1% vs 32.2%; p=0.98), but the rate of prehospital fibrinolysis and the rate of PCI after fibrinolysis became more frequent in “new” registry (50.9% vs 23.5%; p&lt;0.0001 and 52.4% vs 25.0%; p&lt;0.0001 respectively). In patients with non-ST elevation ACS (NSTEACS) the rate of diagnostic coronarography (CAG) and the rate of PCI within 72 hours after admission weren’t significantly different in “new” and “old” registries (68.2% vs 71.8%; p=0.15 and 26.6% vs 23.6%; p=0.19 respectively). Among discharge medication from “old” to “new” registries decreasing of aspirin and beta-blockers prescription (89.7% and 91.3%; p=0.009 and 86.0% vs 90.2%; p&lt;0.0001 respectively) and increasing of dual antiplatelet therapy and statin prescription (82.6% vs 43.7%; p&lt;0.0001 and 90.9% vs 78.1%; p&lt;0.0001 respectively) were obtained.The duration of in-hospital stay in “new” registry was shorter than in “old” registries (10,2 vs 13.4 days; p&lt;0.0001), the proportion of patients transferred in non-PCI-capability centers to CAG was higher (16.3% vs 2.2%; p&lt;0.0001) and the rate of in-hospital death was lower (5.1% vs 6.6%; p=0.041). Conclusion: A series of prospective independent registries RECORDs showed that in recent years some progress towards better adherence to the guidelines has been made in the treatment of ACS in Russian hospitals participating in those registries. However, there wasn’t a clear increase in the rate of pPCI and fibrinolysis in STEMI and the rate of invasive strategy in NSTEACS.

DRIVING TIME TO NEAREST PRIMARY PERCUTANEOUS CORONARY INTERVENTION CENTER AND CHOICE OF REPERFUSION THERAPY FOR ST-ELEVATION MYOCARDIAL INFARCTION

Primary percutaneous coronary intervention (pPCI) is recommended over fibrinolysis for ST-elevation myocardial infarction (STEMI) if first medical contact to balloon time ≤2 hours can be achieved. We evaluated transport time and reperfusion therapy selection in patients treated with PCI for STEMI

Consistency of benefit from an early invasive strategy after fibrinolysis: a patient-level meta-analysis

BackgroundRandomised controlled trials have demonstrated improved outcomes with an early invasive strategy compared with routine care after fibrinolysis among patients with ST-elevation myocardial infarction. However, it remains uncertain whether specific...

Outcomes of patients undergoing percutaneous coronary intervention following fibrinolysis for ST-elevation myocardial infarction

Outcomes of patients undergoing percutaneous coronary intervention following fibrinolysis for ST-elevation myocardial infarction

EFFICACY AND SAFETY OF A ROUTINE EARLY INVASIVE STRATEGY IN RELATION TO TIME FROM SYMPTOM ONSET TO FIBRINOLYSIS: A SUBGROUP ANALYSIS FROM TRANSFER-AMI

Randomized controlled trials have demonstrated the clinical benefit of a routine early invasive strategy in patients receiving fibrinolysis for ST-elevation myocardial infarction (STEMI). However, the treatment effect of fibrinolysis is highly time sensitive - efficacy decreases as the time interval from symptom onset to fibrinolysis lengthens. Whether the effect of a routine early invasive strategy, as an adjunct to fibrinolysis, also varies in relation to this time interval is not well understood. We therefore sought to evaluate the efficacy and safety of a routine early invasive strategy in relation to time from symptom onset to fibrinolysis. The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1059 STEMI patients to an early invasive strategy - consisting of routine early transfer for coronary angiography and percutaneous coronary intervention (PCI) if needed within 6 hours of fibrinolysis - or standard therapy post-fibrinolysis. The primary endpoint was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post-hoc subgroup analysis of TRANSFER-AMI, we evaluated efficacy and safety outcomes after stratification by the time elapsed from symptom onset to fibrinolysis (<2 vs ≥2 hours). Of 1059 patients (median age 57 years, 80% male), 557 (53%) and 502 (47%) received fibrinolysis <2 hours (median 1.25 hours, IQR 0.97-1.58 hours) and ≥2 hours (median 3.24 hours, IQR 2.43-4.80 hours) after symptom onset, respectively. Patients receiving fibrinolysis <2 hours after symptom onset were younger, and more likely to be male and have had a prior myocardial infarction and PCI. Patients who received fibrinolysis ≥2 hours after symptom onset had higher GRACE risk scores (127 vs 122, p=0.004). Baseline characteristics and treatment variables were well balanced between treatment arms within each symptom-to-fibrinolysis time stratum. The efficacy of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary endpoint, death at 30 days, or the composite of death or reinfarction at 30 days, 6 months, or 1 year (Figure). The effect of an early invasive strategy on TIMI major bleeding was also similar between strata. The efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time from symptom onset to fibrinolysis. A routine early invasive strategy is safe and effective even if fibrinolytic is administered shortly (<2 hours) after symptom onset.

Efficacy of an Early Invasive Strategy After Fibrinolysis in ST-Elevation Myocardial Infarction Relative to the Extent of Coronary Artery Disease

BackgroundA strategy of early transfer for coronary angiography and intervention is superior to a standard approach of delayed coronary angiography after fibrinolysis for ST-elevation myocardial infarction (STEMI). STEMI patients with lesions in noninfarct-related arteries have a worse prognosis compared with patients with single vessel disease. This study aimed to assess whether the benefits of an early invasive strategy differ in patients with single vessel and multivessel disease. MethodsThe Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized STEMI patients receiving fibrinolysis to a strategy of early transfer and coronary angiography vs a standard approach. In this post hoc analysis, we stratified 992 patients into 2 groups according to the presence or absence of multivessel disease. We compared the 2 groups in terms of baseline characteristics, in-hospital management, and patient outcomes, and tested for treatment heterogeneity. ResultsMultivessel disease was present in 369 (37%) patients. Patients with multivessel disease had a greater rate of the primary composite end point of in-hospital death, recurrence of infarction, recurrent ischemia, shock, or heart failure at 30 days (18.2% vs 10.8%; P < 0.001). An early invasive strategy was efficacious in both groups for the primary outcome. In multivariable analysis adjusting for Global Registry of Acute Coronary Events (GRACE) risk score, there was no significant treatment heterogeneity (all P interaction > 0.40) for the primary end point, or death/recurrence of infarction at 6 months and 1 year. ConclusionsMultivessel disease is present in a significant proportion of STEMI patients treated with fibrinolysis and is associated with worse outcomes. A strategy of early transfer and coronary intervention after fibrinolysis was beneficial regardless of the presence or absence of multivessel disease.

Is There Still a Role for Fibrinolysis in ST-Elevation Myocardial Infarction?

Fibrinolysis had long been the reference treatment in patients with ST-Elevation Myocardial Infarction (STEMI). It was associated with a large reduction in mortality as compared with delayed or no reperfusion in patients managed early, within the first 2hours from the onset of symptoms. Fibrinolysis also had well-known potential complications: cerebral haemorrhage, especially in patients beyond 75years, and reinfarction. Primary percutaneous intervention (PCI) has overcome most of these limitations, but at a price: PCI-related delays that can reduce the expected benefit of primary PCI compared with fibrinolysis. That primary PCI is today the treatment of choice in patients with STEMI is no longer discussed. However, fibrinolysis should still maintain a role in the management of acute myocardial infarction (AMI) for three reasons. First, fibrinolysis is no longer a stand-alone treatment. Modern fibrinolytic strategies combine immediate fibrinolysis, loading dose of thienopyridines, and transfer to a PCI hospital for rescue or early PCI within 24hours. These strategies capitalize on the hub-and-spoke networks that have, or should have, been built everywhere to implement primary PCI. The overall clinical results of these modern fibrinolytic strategies are now similar to those of primary PCI. Second, a substantial number of patients cannot be managed with primary PCI within the reasonable time thresholds set by the guidelines. In the case of long PCI-related delays, patients will benefit from fibrinolysis before or during transfer to a PCI hospital. Third, modern fibrinolytic strategies-immediate fibrinolysis followed by rescue or early PCI-may even offer the best results of all in a subset of patients. Patients of less than 75years, managed within the first 2hours and who cannot have immediate PCI, will fare better with a modern fibrinolytic strategy than with primary PCI. Guidelines advocate regional networks between hospitals with and without PCI capabilities, an efficient ambulance service and standardization of AMI management through shared protocols. These regional logistics of care are essential to take full advantage of fibrinolysis strategies. In order to check that these strategies are correctly applied, networks need ongoing registries, as well as benchmarking and quality improvement initiatives.

Efficacy and safety of enoxaparin compared with unfractionated heparin in the pharmacoinvasive management of acute ST-segment elevation myocardial infarction: Insights from the TRANSFER-AMI trial

An early invasive strategy after fibrinolysis for ST-elevation myocardial infarction (STEMI) improves outcomes, but the relative efficacy and safety of enoxaparin compared with unfractionated heparin (UFH) as part of this approach are unknown. In the TRANSFER-AMI trial, patients with high-risk STEMI received fibrinolysis and were then randomized to either standard treatment or to immediate transfer for coronary angiography. In this substudy, the outcome of patients aged <75 years treated with enoxaparin is compared with that of patients who received UFH. Logistic regression and propensity score models were used to evaluate the efficacy and safety of these anticoagulants. Enoxaparin was administered to 498 patients, and UFH, to 448 patients, at the time of fibrinolysis. Approximately 50% in each group were randomized to the early invasive strategy. The primary composite end point of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days occurred in 11.9% and 11.6% of the patients who received enoxaparin and UFH, respectively (adjusted odds ratio 0.95 [95% CI 0.60-1.51], P = .84). Enoxaparin use was associated with more access site bleeding (5.0% vs 2.9%, P = .04) and mild bleeding (12.1% vs 7.8%, P = .03). Among high-risk patients with STEMI undergoing early or late transfer for cardiac catheterization after fibrinolysis, enoxaparin was associated with similar efficacy compared with UFH, but there was more minor bleeding with enoxaparin (ClinicalTrials.gov no. NCT00164190).

Relationship between risk stratification at admission and treatment effects of early invasive management following fibrinolysis: insights from the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

We sought to determine the effectiveness of early routine percutaneous coronary intervention (PCI) post-fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to baseline risk status. In this post hoc subgroup analysis of Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), we stratified 1059 STEMI patients receiving tenecteplase into low-intermediate [Global Registry of Acute Coronary Events (GRACE) risk score<155; n=889] vs. high-risk (GRACE risk score ≥155; n=170) groups, based on the GRACE risk score for in-hospital mortality. There was a significant interaction between treatment assignment and risk status for the composite endpoint of death/re-MI at 30 days (P for interaction<0.001). Compared with the standard treatment, pharmacoinvasive therapy (early routine PCI) was associated with a lower rate of death/re-MI at 30 days in the low-intermediate risk stratum (8.1 vs. 2.9%, P<0.001), but a higher rate of death/re-MI in the high-risk group (13.8 vs. 27.8%, P=0.025). We found similar heterogeneity in the treatment effects on 30-day mortality and death/re-MI at 1 year (P for interaction=0.008 and 0.001, respectively), when the GRACE risk score was analysed as a continuous variable (P for interaction<0.001) and when patients were stratified by the Thrombolysis In Myocardial Infarction (TIMI) risk score (P for interaction=0.001). We observed a strong heterogeneity in the treatment effects of a pharmacoinvasive strategy after fibrinolysis for STEMI, which is associated with improved outcomes only among patients with a low-intermediate GRACE risk score. Conversely, the early invasive strategy is associated with worse outcomes in high-risk patients. These novel findings should be considered exploratory only and require confirmation in other trials and meta-analyses. http://www.clinicaltrials.gov/ct2/show/NCT00164190 ClinicalTrials.gov number, NCT00164190.

Prolonged anticoagulation therapy adjunctive to aspirin after successful fibrinolysis: From early reduction in reocclusion to improved long-term clinical outcome

Long-term addition of antithrombotics (clopidogrel, anticoagulants) to aspirin has improved outcome after acute coronary syndromes. Data on the impact after fibrinolysis are scarce. In Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis-2 (APRICOT-2), adjunctive moderate-intensity coumarin (median international normalized ratio 2.6) conferred a marked reduction in 3-month reocclusion and ischemic events. Given the association between reocclusion and long-term outcome, we performed long-term clinical follow-up. Patients with thrombolysis in myocardial infarction (TIMI) 3 flow <48 hours after fibrinolysis for ST-elevation myocardial infarction were randomized to aspirin plus coumarin, with prolonged heparinization until the target international normalized ratio (2-3) was reached, or aspirin with standard heparinization. Three-month follow-up angiography (reocclusion rates 15% vs 28%) and long-term clinical follow-up (median 7.3 years, interquartile range 5.9-8.6 years) were performed. Patients randomized to adjunctive anticoagulation (n = 123) received coumarin for a median of 280 days (113-387 days). Survival was 94% versus 88% in patients on aspirin alone (n = 128, P = .12). Infarct-free survival was 86% versus 71% (P = .01). Thrombolysis in myocardial infarction bleeding was 4% in both groups. Patients with reocclusion had impaired survival: 80% versus 94% (P < .01). In a multivariable model without reocclusion, combination therapy independently predicted survival (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.13-1.00) and infarct-free survival (HR 0.51, 95% CI 0.28-0.95). When adjusted for reocclusion, combination therapy did not predict outcome. Reocclusion independently predicted death (HR 2.56, 95% CI 1.02-6.43) and reinfarction. Moderate-intensity oral anticoagulation added to aspirin improved 8-year clinical outcome after successful fibrinolysis. The beneficial effect was largely attributed to a reduction in reocclusion, which independently predicted death and reinfarction. This study provides a mechanistic rationale for prolonged adjunctive anticoagulation after fibrinolysis.