Multicenter randomized trial of facilitated percutaneous coronary intervention with low‐dose tenecteplase in patients with acute myocardial infarction: The Athens PCI trial

Objectives: To examine the safety and efficacy of low‐dose tenecteplase, administered before facilitated percutaneous coronary intervention (PCI) to restore Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 blood flow in the infarct related artery (IRA) in patients with ST elevation myocardial infarction (STEMI) scheduled to undergo PCI with a shortest anticipated delay of 30 min. Background: PCI preceded by administration of glycoprotein IIb/IIIa inhibitors, full‐dose thrombolytics, or both, is associated with no benefit or a higher incidence of adverse events than PCI alone. Methods: Patients with STEMI < 6 hr in duration were randomly assigned to PCI preceded by tenecteplase, 10 mg (facilitated PCI group, n = 143) versus standard PCI (control group, n = 141). All patients received aspirin and unfractionated heparin (70 IU/kg bolus) at time of randomization. Both groups received IIb/IIIa inhibitors in the catheterization laboratory and for at least 20 hr after PCI. Results: The median door‐to‐balloon time was 122 min (91–175) in the facilitated PCI versus 120 min (89–175) in the control group. IRA patency on arrival in the catheterization laboratory was 59.5% in the facilitated PCI (24% TIMI‐2, 35% TIMI‐3), versus 37% in the control (8% TIMI‐2, 29% TIMI‐3) group (P = 0.0001). During hospitalization, 9 patients (6%) died in the facilitated PCI versus 5 patients (3.5%) in the control group (P = 0.572). A single patient in the facilitated PCI group suffered a non‐fatal ischemic stroke. Conclusions: Facilitated PCI with low‐dose tenecteplase in patients presenting with STEMI was associated with a high IRA patency rate before PCI. © 2009 Wiley‐Liss, Inc.     

Effects of the early administration of heparin in patients with ST-elevation myocardial infarction treated by primary angioplasty.

BACKGROUND: The effect of adjunctive heparin for primary angioplasty in patients with ST-elevation myocardial infarction (STEMI) is not well established, so the authors investigated the effect of early heparin administration in the emergency room (ER) on initial patency of the infarct-related artery (IRA) and on the clinical outcome in STEMI patients. METHODS AND RESULTS: One hundred and twenty consecutive patients who presented with STEMI less than 12 h from pain onset and who were eligible for primary percutaneous coronary intervention were allocated to an early heparin group (heparin administered in ER) or a late heparin group (heparin administered after angiography). In the early heparin group, unfractionated heparin (60 U/kg bolus IV, then 14 U . kg(-1) . h(-1) IV infusion) or enoxaparin (1 mg/kg bolus SC) were administered 144+/-95 min before angioplasty. No significant differences in baseline characteristics were observed between the early heparin group (n=56) and the late heparin group (n=64). However, initial Thrombolysis In Myocardial Infarction (TIMI) flow grade in the IRA was significantly different between the 2 groups (frequency of TIMI 0/1/2/3; 48/4/7/41% vs 70/8/11/11%, early vs late respectively, p=0.002). TIMI 2 or 3 flow was significantly more frequent in the early heparin group than in the late heparin group (48% vs 22%, p=0.002). However, no significant differences were noted between the 2 groups in terms of in-hospital major adverse cardiac events (7% vs 11%, p=0.472) and TIMI major bleeding (2% vs 3%, p=0.639). CONCLUSIONS: In STEMI patients, early heparin therapy administered in the ER improves coronary patency, despite not reaching clinical benefit.     

High Dose Bolus Heparin as Initial Therapy Before Primary Angioplasty for Acute Myocardial Infarction: Results of the Heparin in Early Patency (HEAP) Pilot Study

Objectives. We sought to determine the effect of high dose intravenous bolus heparin on early coronary patency before primary angioplasty.Background. Early coronary angiography after thrombolysis for acute myocardial infarction has shown better patency when intravenous heparin is used as an adjunct. The present study explores whether heparin alone can induce reperfusion.Methods. In the Heparin in Early Patency (HEAP) pilot study, 108 patients with signs and symptoms of acute myocardial infarction <6 h eligible for primary angioplasty received a single intravenous bolus of 300 U/kg of heparin together with aspirin (160 mg chewed) in the emergency room. The median dose of bolus heparin given was 27,000 U. Patency of the infarct-related artery (IRA) was assessed by coronary angiography at a median of 85 min after the heparin bolus.Results. In 55 patients (51%, 95% confidence interval 38% to 64%), Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at 90 min: TIMI flow grade 3 in 33 patients (31%); TIMI flow grade 2 in 22 (20%). Thirty-two (64%) of 50 patients with symptoms ≤2 h had TIMI flow grade 2 or 3 versus 23 (40%) of 58 patients with symptoms >2 h (p = 0.02). No significant bleeding was seen. Two patients (2%) died in the hospital. The patency results obtained in patients treated with the high dose bolus heparin were compared with those in 108 patients from a large primary angioplasty database, who were treated with standard therapy, including aspirin but not intravenous heparin, and were matched for clinical and angiographic characteristics with the HEAP pilot study patients. They showed an 18% patency rate (p < 0.001) of the IRA (TIMI flow grade 3 in 9%, TIMI flow grade 2 in 9%) before primary angioplasty.Conclusions. Early therapy with high dose heparin is associated with full coronary reperfusion in a considerable number of patients with acute myocardial infarction, especially in those treated early (<2 h). This simple, inexpensive, probably safe and easily antagonizable treatment may be an attractive first treatment of acute myocardial infarction both before and during the hospital stay in conjunction with primary angioplasty.     

Optimal strategy for administering enoxaparin to patients undergoing coronary angiography without angioplasty for acute coronary syndromes

The optimal strategy for administration of low molecular weight heparin in patients with acute coronary syndrome (ACS) undergoing coronary angiography without percutaneous coronary intervention remains unclear. We studied postangiographic vascular complications in 325 consecutive patients (210 men and 115 women, mean age 63 years) with ACS undergoing diagnostic coronary angiography via a femoral approach followed by immediate sheath removal. At the time of angiography, 44 patients were on intravenous unfractionated heparin (UFH), 229 on subcutaneous enoxaparin, and 52 on no heparin. Enoxaparin was withheld on the morning of angiography in 181 of 229 patients: the no A.M. dose group. Vascular complications were audited, including hematoma development at angiographic puncture sites; these complications were considered significant if >25 cm(2). Major vascular complications requiring transfusion or surgical interventions were infrequent in all groups. Patients receiving enoxaparin on the morning of angiography had a twofold increase in significant hematoma rate compared with the no A.M. dose group (31% vs 16%; p = 0.015). The no A.M. dose group had hematoma rates similar to UFH (20%; p = NS) and no anticoagulation (13.5%; p = NS). No significant increase in ischemic episodes occurred as a result of withholding enoxaparin in the no A.M. dose group. We conclude that omission of enoxaparin on the morning of cardiac catheterization results in vascular complications rates comparable to that of UFH without precipitating rebound ischemia. This is a practical, safe strategy for patients with ACS undergoing coronary angiography, allowing early mobilization for most patients who do not proceed to immediate percutaneous coronary intervention.     

Randomized comparison of a novel anticoagulant, vasoflux, and heparin as adjunctive therapy to streptokinase for acute myocardial infarction: results of the VITAL study (Vasoflux International Trial for Acute Myocardial Infarction Lysis)

BACKGROUND: Vasoflux is a low-molecular-weight heparin derivative that inhibits factor IXa activation of factor X and catalyzes fibrin-bound thrombin inactivation by heparin cofactor II. We studied whether vasoflux improves the results of thrombolysis with streptokinase for acute myocardial infarction. METHODS AND RESULTS: We randomized 277 patients with acute myocardial infarction to standard intravenous unfractionated heparin (UFH) or intravenous vasoflux 1, 4, 8, or 16 mg/kg as a bolus followed by 1, 4, 8, or 16 mg/kg per hour infusion, on top of streptokinase and aspirin, until angiography at 90 minutes. Patency and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count were studied at 60 and 90 minutes. Rates of TIMI grade 3 flow with vasoflux at any dose (35% to 42%) were not different from UFH (41%) at either time point, nor was the corrected TIMI frame count. However, there was an excess of bleeding in the patients randomized to vasoflux 8 or 16 mg/kg: 78% and 71%, compared with 53% for UFH (P =.004 and.043, respectively). Major bleeding was observed in 13% and 28% at these vasoflux doses compared with 8% with UFH (P =.558 and.01, respectively). CONCLUSION: At doses that increase the risk of bleeding, the addition of vasoflux to streptokinase and aspirin did not lead to improved patency rates compared with UFH. Targeting factor IXa and heparin cofactor II may not be a useful adjunct to thrombolysis.     

Relationship of admission haematological indices with infarct-related artery patency in patients with acute ST-segment elevation myocardial infarction treated with primary angioplasty

OBJECTIVE: Mean platelet volume (MPV), a marker for platelet reactivity, and white blood cell count (WBC-C), a marker for inflammation, have been shown to be predictive of unfavourable outcomes among survivors of ST elevation myocardial infarction (STEMI). The relationship of admission MPV and WBC-C with infarct-related artery (IRA) patency is not clear. We aimed to evaluate the value of admission MPV and WBC-C for the prediction of IRA patency, in patients with acute STEMI treated with primary percutaneous coronary intervention. METHODS: Blood samples were obtained on admission in 351 STEMI patients. The patients who had thrombolysis in myocardial infarction (TIMI) 3 flow in initial angiography constituted the IRA patent group and others having less than TIMI 3 flow constituted the IRA occluded group. RESULTS: In 16% of the patients, IRAs were found to be patent on initial angiography. Patients in the IRA occluded group had higher admission MPVs (9.3+/-1.2 vs. 8.6+/-1.3 fl, P<0.001) and higher WBC-C (13.3+/-4.8 vs. 11.0+/-2.9, P=0.002) compared with patients in the patent IRA group. In regression analysis, WBC-Cs [beta, 0.131; odds ratio (OR), 1.140; 95% confidence interval (CI), 1.043-1.245, P=0.004)] and MPV (beta, 0.519; OR, 1.680; 95% CI, 1.206-2.339, P=0.002) were found to be independent predictors of occluded IRA. The best cutoff value of MPV for predicting an occluded IRA was determined to be 8.55 fl with a sensitivity of 74% and a specificity of 60%. CONCLUSION: MPV and WBC-C at admission might be valuable in the prediction of IRA patency and in planning the need for adjunctive therapy to improve outcomes in patients with STEMI undergoing percutaneous coronary intervention.     

Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism

BACKGROUND: Few reports have addressed the value of unfractionated heparin (UFH) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism. METHODS: In an open, multicenter clinical trial, 720 consecutive patients with acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm (preceded by an intravenous loading dose), or fixed-dose (adjusted only to body weight) subcutaneous nadroparin calcium. Oral anticoagulant therapy was started concomitantly and continued for at least 3 months. We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up. RESULTS: Fifteen (4.2%) of the 360 patients assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%) of the 360 patients assigned to nadroparin (absolute difference between rates, 0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2% to 1.7%). Overall mortality was 3.3% in each group. CONCLUSIONS: Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE, including those with pulmonary embolism and recurrent VTE.     

Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study.

BACKGROUND: Current thrombolytic-antithrombotic regimens in acute myocardialinfarction (AMI) are limited by incomplete early coronary reperfusion and by reocclusion and reinfarction. We compared the effects of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as an adjunct to recombinant tissue-plasminogen activator (alteplase) on coronary artery patency and clinical outcomes in AMI. METHODS: Patients with AMI treated with alteplase (n=439) were randomised to either subcutaneous dalteparin (120 IU/kg every 12h) for 4-7 days or intravenous infusion of UFH for 48 h. Coronary angiography was performed between day 4 and hospital discharge. Clinical events and safety were evaluated until day 30. RESULTS: Overall there were higher thrombolysis in myocardial infarction (TIMI) flows in the infarct related coronary artery in the dalteparin group (p=0.016). The predefined primary end-point, TIMI grade 3 flow, did not reach statistical significance (dalteparin 69.3% versus heparin 62.5%; p=0.163). However, TIMI 0-1 flow (13.4 versus 24.4%; p=0.006) and its combination with intraluminal thrombus (27.9 versus 42.0%; p=0.003) were less common in the dalteparin group. During the period of randomised treatment there were less myocardial reinfarctions in the dalteparin group(p=0.010) but after cessation of dalteparin there were more reinfarctions resulting in no difference in death or MI at 30 days. There were no significant differences in major bleeding or stroke after 30 days. CONCLUSIONS: In alteplase treated AMI adjunctive dalteparin for 4-7 days seems to reduce the risk of early coronary artery occlusion and reinfarction. However, early after cessation of treatment there is a raised risk of events, which might eliminate any long-term gains.     

Prehospital administration of enoxaparin before primary angioplasty for ST-elevation acute myocardial infarction.

We hypothesized that primary percutaneous coronary intervention (PCI) could be performed with prehospital injections of enoxaparin for ST segment elevation myocardial infarction (STEMI). Enoxaparin has been studied in combination with fibrinolysis in STEMI, but has not been evaluated as anticoagulant regimen for primary PCI. In a prospective registry, 143 consecutive patients with STEMI received prehospital 0.5 mg/kg intravenous (i.v.) bolus followed by 1 mg/kg subcutaneous enoxaparin before immediate transport for PCI. We focused on anti-Xa activities before and after PCI, bleedings, infarct-related artery patency, and major adverse cardiac events at day 30. Anti-Xa activity was at the target level (>0.5 IU/ml) in 99% of patients during PCI, and in 100% 4 hr after injections; over-anticoagulation (>1.5 IU/ml) was noted in 9 and 2%, respectively at start and 4 hr after injections. Bleeding complications with enoxaparin were rare: major in 1.4% (no intracranial hemorrhages), minor in 2.1%. A patent infarct-related artery (TIMI 2 + 3) was observed in 40.6% of the patients before PCI. TIMI 3 flow was obtained in 88.1% of the cases after PCI. Major adverse cardiac events at 30 days occurred in 5.6% of cases: death 2.8%, reinfarction 3.5%, and target lesion revascularisation 3.5%. Prehospital i.v. and subcutaneous enoxaparin provides simple and rapid anticoagulation for PCI in STEMI patients. Enoxaparin dose needs to be reduced regarding the 9% of over-anticoagulation. This study suggests the potential of enoxaparin as an alternative anticoagulant regimen for primary PCI.     

Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel. BACKGROUND: The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined. METHODS: We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use. RESULTS: Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj) 0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (p(interaction) = 0.61). CONCLUSIONS: In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI.     

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention

Objectives : The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI). Background : Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. Methods : Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié‐Salpêtrière registry of ischemic coronary syndromes (e‐PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity‐weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. Results : Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti‐Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12–0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16–0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12–0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17–0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). Conclusions : In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley‐Liss, Inc.     

Effects of direct stenting on epicardial and myocardial perfusion in patients with acute ST segment elevation myocardial infarction

BACKGROUND: Results of studies comparing direct stenting (DS) with conventional stenting (CS) after balloon predilatation in patients with acute myocardial infarction (MI) have been reported in the past, however they are conflicting. There are only few randomised studies that aim to answer whether DS improves epicardial and myocardial patency. AIM: To assess the effects of DS on epicardial and myocardial patency in patients with acute MI. METHODS: Consecutive patients with acute MI were randomised either to DS or CS strategy. Clinical exclusion criteria were as follows: clinical and electrocardiographic features of reperfusion, pulmonary oedema, cardiogenic shock, contradictions to coronarography, allergy to aspirin, ticlopidine, clopidogrel, heparin and stainless steel. Angiographic exclusion criteria were as follows: lesion <50% with correct patency in the infarct-related artery (IRA), lesion in the left main coronary artery, previously performed percutaneous coronary intervention in the target vessel, diameter of the IRA <2 mm or >4 mm. We assessed epicardial patency according to the TIMI (thrombolysis in myocardial infarction) scale and myocardial patency according to the TMPG (TIMI myocardial perfusion grade) scale. In addition, we analysed ST segment resolution in 12-lead electrocardiography (ECG). The ECG was performed before and 30 minutes after PCI. RESULTS: We analysed 300 consecutive patients with acute ST segment elevation MI. After exclusion of patients not suitable for the study design, the DS group comprised 110 patients and the CS group - 107 patients. Clinical and angiographic results were similar in both groups. Initial TIMI 0 (48.2% vs. 43.0%), initial TIMI 3 (31.8% vs. 28.0%), initial TMPG 0-1 (77.3% vs. 78.5%), final TIMI 3 (95.5% vs. 93.5%) and final TMPG 2-3 (68.2% vs. 60.8%) were similar in the DS and CS groups, respectively (p=NS). The incidence of no-reflow phenomenon was comparable in both groups (4.5% vs. 6.5%, NS). The inclusive rate of no-reflow phenomenon plus worsening patency in the IRA were 6.4% vs. 10.3% in the DS and CS groups respectively. The ST segment resolution > or = 50% was 58.1% in the DS group and 56.1% in the CS group (NS). CONCLUSIONS: Direct stenting does not significantly improve epicardial and myocardial patency in an unselected group of patients with acute ST segment elevation MI.     

Recurrent venous thrombosis and heparin therapy: an evaluation of the importance of early activated partial thromboplastin times.

BACKGROUND: The presence of an association between early subtherapeutic activated partial thromboplastin times (aPTTs) and recurrent venous thromboembolism (VTE) remains controversial. OBJECTIVE: To determine the relation between early subtherapeutic aPTTs and recurrent VTE in patients who were treated with intravenous (i.v.) unfractionated heparin (UFH). PATIENTS AND METHODS: We studied 961 patients with acute VTE who received i.v. UFH in 3 randomized trials that compared the use of i.v. UFH (loading dose: 5000 U i.v.; initial infusion, 1250-1280 U/h) with that of subcutaneous low-molecular-weight heparin. According to aPTT criteria, patients were classified as being in a subtherapeutic or a therapeutic state during the first 24 and 48 hours of treatment. All episodes of possible recurrent VTE were adjudicated by an independent committee that was unaware of the aPTTs. RESULTS: At 24 hours, in 886 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 6.7% (11/163) compared with 5.3% (38/723) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 24 hours was 1.30 (95% confidence interval: 0.64-2.63; P = .46). At 48 hours, in 917 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 7.8% (5/64) compared with 5.7% (49/853) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 48 hours was 1.32 (95% confidence interval: 0.51-3.44; P = .56). CONCLUSION: In patients with acute VTE who receive an i.v. bolus of 5000 U, followed by a starting dose of at least 1250 U/h of UFH, a subtherapeutic aPTT response during the first 48 hours of treatment is not associated with a large increase in the risk of recurrent VTE.     

Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.

OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and subsequently undergo percutaneous coronary intervention (PCI) by analyzing data from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial. BACKGROUND: Limited data are available on the use of ENOX compared with UFH as adjunctive therapy in STEMI patients treated with fibrinolytic therapy and subsequent PCI. METHODS: A total of 20,479 STEMI patients who received fibrinolytic therapy were randomized to a strategy of ENOX throughout index hospitalization or UFH for at least 48 h, with blinded study drug to continue if PCI was performed. The primary end point of death or recurrent MI through 30 days was compared for ENOX versus UFH among the patients who underwent subsequent PCI (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027). Among patients who underwent PCI by 30 days, the primary end point occurred in 10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p = NS). Results were similar when PCI was carried out in patients receiving blinded study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration was associated with a reduced risk of death or recurrent MI without difference in the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy followed by PCI is superior to UFH and provides a seamless transition from the medical management to the interventional management phase of STEMI without the need for introducing a second anticoagulant in the cardiac catheterization laboratory.     

T wave inversions in leads with ST elevations in patients with acute anterior ST elevation myocardial infarction is associated with patency of the infarct related artery

Objectives

Following reperfusion therapy, early T wave inversions (TWI) have been shown to be a marker of successful reperfusion. We aimed to evaluate the relationship of TWI on the presenting ECG with spontaneous reperfusion as assessed by coronary angiography in patients with ST elevation (STE) myocardial infarction (STEMI).

Methods

Data of 146 consecutive patients presenting to the St. Luke's Episcopal Hospital Emergency Department with acute STEMI undergoing primary percutaneous coronary intervention (p-PCI) between January, 2007 and October, 2010 were retrospectively analyzed. Clinical data, ECG and angiographic data were reviewed. Patients were dichotomized based on T wave morphology on the presenting ECG into 2 groups – those with TWI and those with positive T waves (PTW).

Results

Thirty-one patients (21.2%) had TWI, while 115 (78.8%) had PTW. Sixty-four (43.8%) patients had anterior STE and 75 (51.3%) had inferior STE. Anterior STE was more likely to have TWI than non-anterior (29.7% vs. 14.6; p = 0.014). By angiography, infarct related artery (IRA) patency (TIMI 2–3 flow) was seen in 45 (30.8%). TWI was more likely to be associated with IRA patency compared to PTW (51.6% vs. 25.2%; p = 0.008). In patients with anterior STEMI and TWI, patent IRA was seen more frequently compared to those with PTW (68.4% vs. 20%; p < 0.001). There was no association of T wave morphology and TIMI flow in patients with non-anterior STEMI. Patients presenting with stuttering symptoms were more likely to have TWI (70.4% vs. 10.2%; p < 0.001) suggesting recurrent episodes of reperfusion and ischemia.

Conclusions

In anterior STEMI patients, TWI on the presenting ECG is associated with spontaneous reperfusion. This relationship was not found among patients with non-anterior STEMI.     

Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism

BACKGROUND: Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE). OBJECTIVE: To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE. MATERIAL AND METHODS: After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death. RESULTS: In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318). CONCLUSION: Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.     

Impact of Timing of Eptifibatide Administration on Preprocedural Infarct-Related Artery Patency in Acute STEMI Patients Undergoing Primary PCI

The appropriate timing of eptifibatide initiation for acute ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) remains unclear. This study aimed to analyze the impact of timing of eptifibatide administration on infarct-related artery (IRA) patency in STEMI patients undergoing primary PCI. Acute STEMI patients who underwent primary PCI (n = 324) were enrolled in this retrospective study; 164 patients received eptifibatide bolus ≤ 30 minutes after emergency department (ED) admission (group A) and 160 patients received eptifibatide bolus > 30 minutes after ED admission (group B). The primary endpoint was preprocedural IRA patency. Most patients in group A (90%) and group B (89%) were late presenters (> 2 hours after symptom onset). The two groups had similar preprocedural thrombolysis in myocardial infarction 2 or 3 flow of the IRA (26 vs. 24%, p = not significant [NS]), similar creatine kinase-MB (CK-MB) levels at 8 hours after admission (339 vs. 281 U/L, p = NS), similar left ventricular ejection fraction (LVEF) (52 vs. 50%, p = NS), and similar 30-day mortality (2 vs. 7%, p = NS). Compared with group B, patients in group A had shorter door-to-device time (p < 0.001) and shorter procedural time (p = 0.004), without increased bleeding risk (13 vs. 18%, p = NS). Earlier intravenous administration of eptifibatide before primary PCI did not improve preprocedural IRA patency, CK-MB level at 8 hours after admission, LVEF and 30-day mortality compared with patients who received intravenous eptifibatide that was administered later.     

Defibrotide versus heparin in the prevention of coronary reocclusion after thrombolysis in acute myocardial infarction

Summary A multicenter controlled study versus heparin was conducted to explore the activity of defibrotide, a polydesoxy-ribonucleotide drug, in preventing reocclusion after urokinase thrombolysis in patients with acute myocardial infarction (AMI). The study involved 137 consecutive patients with AMI and a time from the onset of symptoms 6 hours, treated with urokinase (1,000,000 U intravenous bolus followed by 1,000,000 U slow-drip infusion over 12 hours). Immediately after thrombolysis, patients were allocated to treatment with defibrotide (group D: day 0, 3.6 g by intravenous infusion in 12 hours; days +1 to +6, 800 mg tid intravenously; days +7 to +10/+12, 400 mg tid intramuscularly), or heparin (group H: day 0, 1000 IU/hour infused over 12 hours; days +1 to +10/+12, 5000 IU tid subcutaneously). Coronary angiography was done, whenever possible, at +10/+12 days. The following parameters were assessed: (a) noninvasive estimate of myocardial reperfusion, through the analysis of CPK time-activity curves; (b) incidence of infarct-related artery (IRA) patency (TIMI scores 2–3) at coronary angiography. A total of 125 patients had a complete enzymatic curve (63 in group D and 62 in group H) and 106 had coronary angiography as well. IRA patency (the main end point) was observed in 63% of group D versus 43% of group H patients (p=0.07). No statistically significant differences were found in the proportion of patients with indirect signs of early reperfusion (63% in group D versus 52% in group H patients). Combining the findings of CPK curve analysis and coronary angiographic data, the D group showed a trend towards a minor proportion of patients with reocclusion of a possibly patent IRA (28% vs. 47%) and a greater proportion of patients with late reperfusion of a possibly occluded IRA (44% vs. 37%), in comparison to the H group. These preliminary data suggest that defibrotide is equal, if not more effective than heparin, in combination with urokinase, in achieving IRA patency in patients with AMI.     

Influence of prehospital administration of aspirin and heparin on initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction

OBJECTIVES: The aim of this study was to investigate the influence of prehospital administration of aspirin and heparin on the initial patency of the infarct-related artery (IRA) in patients with acute myocardial infarction (MI). BACKGROUND: Prehospital diagnosis of acute MI facilitates early pharmacologic intervention on the way to the catheterization laboratory for primary angioplasty. METHODS: We studied the angiographic data and 30-day clinical outcome of 1,702 patients treated with primary angioplasty; 860 received aspirin and heparin before transportation to our hospital and 842 received aspirin and heparin in our hospital. RESULTS: The Thrombolysis In Myocardial Infarction (TIMI) 2 or 3 flow in the IRA was higher in the prehospital treated group (31% vs. 20%, relative risk 0.65, 95% confidence interval 0.55 to 0.78, p < 0.001). Patients with TIMI 2 or 3 flow on the initial angiogram had a higher angioplasty success rate (94% vs. 89%, p < 0.001), a smaller enzymatic infarct size, a higher left ventricular ejection fraction and a lower 30-day mortality (1.6% vs. 3.4%, p = 0.04). CONCLUSIONS: Prehospital administration of aspirin and heparin results in a higher initial patency of the IRA in patients with acute MI.     

Quantitative myocardial contrast echocardiography for prediction of thrombolysis in myocardial infarction flow in acute myocardial infarction

Clinical evaluation of arterial patency in acute ST-elevation myocardial infarction (STEMI) is unreliable. We sought to identify infarction and predict infarct-related artery patency measured by the Thrombolysis In Myocardial Infarction (TIMI) score with qualitative and quantitative intravenous myocardial contrast echocardiography (MCE). Thirty-four patients with suspected STEMI underwent MCE before emergency angiography and planned angioplasty. MCE was performed with harmonic imaging and variable triggering intervals during intravenous administration of Optison. Myocardial perfusion was quantified offline, fitting an exponential function to contrast intensity at various pulsing intervals. Plateau myocardial contrast intensity (A), rate of rise (beta), and myocardial flow (Q = A x beta) were assessed in 6 segments. Qualitative assessment of perfusion defects was sensitive for the diagnosis of infarction (sensitivity 93%) and did not differ between anterior and inferior infarctions. However, qualitative assessment had only moderate specificity (50%), and perfusion defects were unrelated to TIMI flow. In patients with STEMI, quantitatively derived myocardial blood flow Q (A x beta) was significantly lower in territories subtended by an artery with impaired (TIMI 0 to 2) flow than those territories supplied by a reperfused artery with TIMI 3 flow (10.2 +/- 9.1 vs 44.3 +/- 50.4, p = 0.03). Quantitative flow was also lower in segments with impaired flow in the subtending artery compared with "normal" patients with TIMI 3 flow (42.8 +/- 36.6, p = 0.006) and all segments with TIMI 3 flow (35.3 +/- 32.9, p = 0.018). An receiver-operator characteristic curve derived cut-off Q value of <11.3, representing impaired myocardial flow, was 73% sensitive and 67% specific for TIMI <3 flow at angiography. Thus, qualitative MCE identifies patients with STEMI but provides no information regarding infarct-related artery patency, whereas quantitative MCE can predict impaired flow in patients with acute STEMI.