Effect of stent implantation on blood pressure control in adults with coarctation of the aorta.

BACKGROUND: Stenting of coarctation of the aorta (CoA) generally results in good angiographic results and a decrease in transcoarctation pressure gradient. However, effect on blood pressure control is less clear. The goal of the current retrospective analysis was to investigate the effects of CoA stenting on blood pressure control. METHODS: A retrospective analysis was conducted in consecutive adult patients with a CoA who underwent a percutaneous intervention at one of the three participating hospitals. Measurements included office blood pressure, invasive peak-to-peak systolic pressure over the CoA, diameter of the intima lumen at the narrowest part of the CoA and use of medication. The follow-up data were obtained, based on the most recent examination date. RESULTS: There were 26 native CoA and 17 recurrent CoAs (total n = 43). Seven of them underwent two procedures. Mean peak-to-peak gradient decreased from 27 mmHg to 3 mmHg (p < 0.001), and minimal diameter increased from a mean of 11 mm to 18 mm (p < 0.001). Mean systolic blood pressure decreased from 151 ±â€¯18 mmHg to 135 ±â€¯19 mmHg at first follow-up of 3.8 ±â€¯1.9 months and 137 ±â€¯22 mmHg at latest follow-up of 19.5 ±â€¯10.9 months (p = 0.001 and p = 0.009, compared to baseline, respectively). The total number of hypertensive patients decreased from 74% to 27% at latest follow-up. No significant change in antihypertensive medication was observed. CONCLUSION: A clinically significant decrease in systolic blood pressure of approximately 16 mmHg was shown after (re)intervention in CoA patients, which sustained at follow-up. This sustained decrease of blood pressure can be expected to lead to less future adverse cardiovascular events.

Evening intake of aspirin is associated with a more stable 24-h platelet inhibition compared to morning intake: a study in chronic aspirin users.

Daily generation of novel platelets may compromise aspirin's platelet inhibitory action, especially near the end of the regular 24-h dosing interval. A contributor to this attenuation could be the endogenous circadian rhythm. The primary objective of this study was to assess platelet activity 12 and 24 h after different times of aspirin intake (c.q. 8.00 AM and 8.00 PM). A randomized open-label crossover study was conducted, comprising outpatients with stable cardiovascular disease taking aspirin once daily. We measured platelet aggregation with the platelet function analyzer (PFA)-200(®) and light transmission aggregometry (LTA). The attenuation of aspirin's inhibitory action was most apparent in the 8.00 AM regimen. The platelet function analyzer-closure time was 78 s faster at 24 h than at 12 h after intake in the 8.00 AM regimen (IQR: 166.8-301 vs. 132.8-301; p = 0.006) and 0 s faster at 24 h than at 12 h after intake in the 8.00 PM regimen (IQR: 198.8-837.0 vs. 169.8-301; p = 0.653). The adenosine diphosphate 1.0 µmol/L maximum amplitude was 5.40% higher at 24 h than at 12 h after intake in the 8.00 AM regimen (95% confidence interval (CI): -0.03--10.8; p = 0.040) and was 0.75% higher 24 h than at 12 h after intake in the 8.00 PM regimen (95% CI: -4.83-3.33; p = 0.705). The platelet inhibitory effect of aspirin decreases after 24 h, particularly after intake in the morning. These results suggest that patients might benefit from evening intake or twice daily intake regimens.

Long-term follow-up of the viability guided angioplasty after acute myocardial infarction (VIAMI) trial.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia. In non-high risk patients, with proven viability in the infarct-area, the VIAMI trial showed benefit of early in-hospital stenting of the infarct-related coronary artery for the composite of death, myocardial infarction (MI), or unstable angina (UA) at 1 year follow-up. In this study we evaluated the long-term outcome (median 8 years) of patients included in the VIAMI-trial. METHODS: After being stable during the first 48 h of their acute MI, we randomly assigned 216 patients with viability to an invasive (PCI) or a conservative (ischemia-guided) strategy. The primary outcome was the composite endpoint of death from any cause, recurrent myocardial infarction, or unstable angina. The secondary outcome of this study was the need for (repeat) revascularization. RESULTS: The combined endpoint of death, recurrent MI and UA was 20.8% in the invasive group and 32.7% in the conservative group (hazard ratio 0.59; 95% CI 0.36-0.99, p = 0.049). No differences were seen in death (8.5% vs. 8.2%, p = 0.80) or MI (7.5% vs. 10.9%, p = 0.48). Only UA showed a significant difference (4.7% vs. 13.6%, p = 0.002). Repeated revascularization was performed in 22.6% of the invasive group and 41.8% of the conservative group (hazard ratio 0.43; 95% CI 0.29-0.74, p < 0.001).` CONCLUSION: In patients with acute MI (treated with thrombolysis or without reperfusion therapy) and proven viability in the infarct-area, we demonstrated a long-term benefit of early in-hospital stenting of the infarct-related coronary artery.

Left ventricular remodeling after acute myocardial infarction: the influence of viability and revascularization - an echocardiographic substudy of the VIAMI-trial.

BACKGROUND: Viability seems to be important in preventing ventricular remodeling after acute myocardial infarction (AMI). We investigated the influence of viability, as demonstrated with low-dose dobutamine echocardiography, and the role of early revascularization on the process of left ventricular (LV) remodeling after AMI. METHODS: We retrospectively investigated 224 patients who were initially included in the viability-guided angioplasty after acute myocardial infarction-trial (VIAMI-trial). Patients in the VIAMI-trial did not undergo a primary or rescue percutaneous coronary intervention and were stable in the early in-hospital phase. Patients underwent viability testing within 72 hours after AMI. Patients with viability were randomized to an invasive strategy or an ischemia-guided strategy. Follow-up echocardiography was performed at a mean of 205 days. In this echocardiographic substudy, patients were divided into three new groups: group 1, viable and revascularized before follow-up echocardiogram; group 2, viable, but medically treated; and group 3, non-viable patients. RESULTS: Group 1 showed preservation of LV volume indices. The ejection fraction (EF) increased significantly from 54.0% to 57.5% (P = 0.047). Group 2 showed a significant increase in LV volume indices with no improvement in EF (53.3% versus 53.0%, P = 0.86). Group 3 showed a significant increase in LV volume indices, with a decrease in EF from 53.5% to 49.1% (P = 0.043). Multivariate logistic regression analysis indicated the number of viable segments and revascularization during follow-up as independent predictors for EF improvement, especially in patients with lower EF at baseline. CONCLUSION: Viability early after AMI is associated with improvement in LV function after revascularization. When viable myocardium is not revascularized, the LV tends to remodel with increased LV volumes, without improvement of EF. Absence of viability results in ventricular dilatation and deterioration of EF, irrespective of revascularization status. TRIAL REGISTRATION: NCT00149591 (assigned: 6 September 2005).

Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial).

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA). METHODS: Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded. RESULTS: The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051). CONCLUSION: We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00149591.

Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: pilot of the Sonolysis study.

In animal studies, transthoracic ultrasound and microbubbles have shown to dissolve thrombi in ST elevation myocardial infarction (STEMI). To examine this effect in patients, we have initiated the Sonolysis trial. In this pilot study of 10 patients with a first acute STEMI, we investigated the safety and feasibility of this trial. After pretreatment in the ambulance, five patients were randomized to receive microbubbles with three-dimensional (3-D) guided high mechanical index impulses (1.18) for 15 min, whereas the control group received placebo without ultrasound. Subsequently, primary percutaneous coronary intervention (PPCI) was performed, if indicated. All patients successfully underwent study treatment and PPCI. No significant difference between treatment and control group in safety (minor adverse events 2/5 vs. 2/5, p = NS) and outcome (TIMI III flow 3/5 vs. 1/5 respectively, p = 0.23) was recorded. These results demonstrate that the study protocol is feasible in the acute cardiac care setting and safe during treatment and follow-up.

Rationale and design of a trial on the effect of high dose statins on cardiovascular risk in adults after successful coarctation repair.

BACKGROUND: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful coarctation repair. The effect of statins on cardiovascular risk in adults after successful coarctation repair has not yet been established. METHODS: We designed a multicentre, prospective, randomised, open label trial to evaluate the effect of the HMGcoA-reductase-inhibitor (Atorvastatin) on atherosclerotic progression in adult post-coarctectomy patients. The primary endpoint in this study is the carotid intima-media thickness as measured by Bmode ultrasonography of the carotid arteries. CONCLUSION: This large prospective, randomised, open label trial will establish the effect of HMG-coA-reductase inhibitors (Atorvastatin) on cardiovascular risk in adult patients after successful coarctation repair.

Turning 18 with congenital heart disease: prediction of infective endocarditis based on a large population.

AIMS: The risk of infective endocarditis (IE) in adults with congenital heart disease is known to be increased, yet empirical risk estimates are lacking. We sought to predict the occurrence of IE in patients with congenital heart disease at the transition from childhood into adulthood. METHODS AND RESULTS: We identified patients from the CONCOR national registry for adults with congenital heart disease. Potential predictors included patient characteristics, and complications and interventions in childhood. The outcome measure was the occurrence of IE up to the age of 40 and 60. A prediction model was derived using the Cox proportional hazards model and bootstrapping techniques. The model was transformed into a clinically applicable risk score. Of 10 210 patients, 233 (2.3%) developed adult-onset IE during 220 688 patient-years. Predictors of IE were gender, main congenital heart defect, multiple heart defects, and three types of complications in childhood. Up to the age of 40, patients with a low predicted risk (<3%) had an observed incidence of less than 1%; those with a high predicted risk (≥3%) had an observed incidence of 6%. The model also yielded accurate predictions up to the age of 60. CONCLUSION: Among young adult patients with congenital heart disease, the use of six simple clinical parameters can accurately predict patients at relatively low or high risk of IE. After confirmation in other cohorts, application of the prediction model may lead to individually tailored medical surveillance and educational counselling, thus averting IE or enabling timely detection in adult patients with congenital heart disease.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The smoker's paradox after successful fibrinolysis: reduced risk of reocclusion but no improved long-term cardiac outcome.

BACKGROUND: In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. METHODS: In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery <48 h after fibrinolysis received randomized antithrombotic treatment until 3-month follow-up angiography. Five-year clinical follow-up was complete. RESULTS: Current smokers (317 patients, 64%) had favorable clinical (age 54 vs. 60 years, P < 0.01) and angiographic (single vessel disease 61% vs. 49%, P = 0.02) baseline characteristics. Reocclusion rates were 21% (67/317) in smokers versus 32% (59/182) in non-smokers (P < 0.01). Five-year infarct-free cardiac survival did not differ: 82% vs. 85%. Reocclusion (HR 2.41, 95%CI 1.05-5.56, P = 0.04) independently predicted cardiac mortality. Smoking was independently associated with a reduced risk of reocclusion (OR 0.58, 95%CI 0.37-0.91, P = 0.02), but not with improved 5-year cardiac outcome (HR 1.34, 95%CI 0.79-2.25, P = ns). CONCLUSIONS: After successful fibrinolysis, smoking is independently associated with a more than 40% reduced risk of reocclusion, which is an independent predictor of adverse outcome. However, even with more favorable baseline characteristics smokers did not have improved 5-year cardiac outcome in this low-risk population.

Sustained coronary patency after fibrinolytic therapy as independent predictor of 10-year cardiac survival Observations from the Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT) trial.

BACKGROUND: Whether late coronary patency after myocardial infarction has prognostic impact independent of left ventricular function remains a matter of debate. Reocclusion rates in the first year after fibrinolysis vary between 20% and 30%. Of all reocclusions, about 30% present as clinical reinfarction, associated with a 2-fold-increased risk of mortality. The clinical impact of reocclusion that presents without reinfarction has not been studied; but an association has been demonstrated with impaired contractile recovery of left ventricular function, the strongest prognosticator of long-term outcome. We therefore studied the impact of 3-month coronary patency after successful fibrinolysis on 10-year cardiac survival. METHODS: In the APRICOT-1 trial, 248 ST-elevation myocardial infarction patients with an open infarct artery 24 hours after fibrinolysis had 3-month repeated angiography. Ten-year clinical follow-up was complete in 99.6%. RESULTS: The reocclusion rate was 29% (71/248). Of these reocclusions, 24% presented as clinical reinfarction (17/71). Cardiac survival at 10 years was 73% in patients with a reoccluded infarct artery and 88% in patients with sustained patency (P < .01). This difference was also present in patients in whom reocclusion was only detected as a result of systematic repeated angiography, that is, in the absence of reinfarction or ischemic symptoms between angiograms (70% vs 86%, P < .03). Multivariable analysis identified sustained patency at 3-month angiography as independent predictor of 10-year cardiac survival (hazard ratio 2.10, 95% CI 1.10-4.02) together with left ventricular ejection fraction. CONCLUSIONS: Sustained infarct artery patency in the first 3 months after successful fibrinolysis is a strong predictor of 10-year cardiac survival, independent of left ventricular function. Notably, this also holds true when reocclusion occurs without signs of clinical reinfarction or recurrent ischemia. Therefore, future preventive strategies should also focus on "clinically silent" reocclusions. Additional studies on better antithrombotic regimens and the combination with a routine invasive strategy early after successful fibrinolysis are warranted.

High-grade infarct-related stenosis after successful thrombolysis: strong predictor of reocclusion, but not of clinical reinfarction.

BACKGROUND: After successful thrombolysis, a high-grade stenosis at 24-hour angiography is strongly predictive of reocclusion and is often believed to result in high reinfarction rates. However, routine angioplasty did not reduce death or reinfarction in past trials. Systematic angiographic follow-up shows that reocclusion often occurs without clinical reinfarction. This study investigates whether the increased risk for reocclusion associated with a high-grade lesion translates into impaired clinical outcome. METHODS: In the ischemia-guided Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT-1) trial, 240 patients with ST-elevation MI who had an open infarct artery 24 hours after thrombolysis had 3-month repeat angiography to assess reocclusion, with clinical follow-up at 3 months and 3 years. RESULTS: On the basis of the optimal discriminative stenosis severity, the reocclusion rate was 40% (47/118) in patients with a high-grade residual stenosis and 16% (20/122) in patients with a low-medium-grade lesion (risk ratio [RR], 2.43; 95% CI, 1.54-3.84; P <.01). Three-month death and reinfarction rates did not differ: 6% (7/118) versus 9% (11/122; RR, 0.66; 95% CI, 0.26-1.64; P = not significant). Systematic angiographic follow-up revealed that reocclusion of a high-grade lesion occurred in the absence of clinical reinfarction in 85% (40/47) of patients, as compared with 45% (9/20) in patients with a low-medium-grade stenosis (RR, 1.89; 95% CI, 1.15-3.12; P <.01). Despite an independent association with reocclusion, a high-grade stenosis was not predictive of either short- or long-term death and reinfarction. CONCLUSIONS: After successful thrombolysis and adopting an ischemia-guided revascularization strategy, patients with a high-grade stenosis experience death/reinfarction rates similar to that of patients with a low-medium-grade lesion. This is true despite a 2- to 3-fold higher risk for reocclusion. The finding that reocclusion of a high-grade lesion often occurs without clinical reinfarction explains the absence of a relationship between a severe stenosis and death/reinfarction. Appreciation of these observations may contribute to an optimal design of a future randomized trial to re-evaluate the impact of a routine invasive strategy.

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial).

BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery.Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care).The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction.

Relation between exercise-induced hypertension and sustained hypertension in adult patients after successful repair of aortic coarctation.

OBJECTIVES: To investigate whether exercise-induced hypertension in successfully repaired adult post-coarctectomy patients is associated with hypertension on 24-h blood pressure measurement and increased left ventricular mass. METHODS: One hundred and forty-four consecutive post-coarctectomy patients (mean age 31.5 years, range 17-74 years; mean age at repair 7.9 years, range 0-45 years) from three tertiary referral centres were studied using ambulatory blood pressure monitoring, treadmill exercise testing and echocardiography. RESULTS: Of the 144 patients, 27 (19%) were known to have sustained hypertension, based on their history, and all were on antihypertensive medication. However, 32 (27%) of the remaining 117 patients showed elevated mean daytime systolic blood pressure readings at 24-h ambulatory blood pressure monitoring (systolic blood pressure > or = 140 mmHg). Of the remaining 85 patients with normal mean daytime systolic blood pressure, 18 patients (21%) had exercise-induced hypertension (maximal exercise systolic blood pressure > 200 mmHg). Mean daytime systolic blood pressure was higher in the exercise-induced hypertensive patients compared to the normotensive patients with normal exercise blood pressure (134 +/- 5 versus 129 +/- 7 mmHg, P = 0.008). By multivariate analysis, both maximal exercise systolic blood pressure (P = 0.007) and resting systolic blood pressure (P < 0.0001) were independently associated with mean daytime systolic blood pressure. Maximal exercise systolic blood pressure had no independent predictive value for left ventricular mass (P = 0.132). CONCLUSIONS: In adult post-coarctectomy patients, maximal exercise systolic blood pressure is independently associated with mean daytime systolic blood pressure at ambulatory blood pressure monitoring. In this study no independent predictive value of maximal exercise systolic blood pressure for left ventricular mass could be demonstrated.

Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial.

BACKGROUND: Despite the use of aspirin, reocclusion of the infarct-related artery occurs in approximately 30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. METHODS AND RESULTS: At coronary angiography <48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (< or =TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P<0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P<0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively (P<0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% (P=NS). CONCLUSIONS: As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.