Abciximab in the treatment of acute myocardial infarction eligible for primary percutaneous transluminal coronary angioplasty. Results of the Glycoprotein Receptor Antagonist Patency Evaluation (GRAPE) pilot study.

OBJECTIVES: We sought to study the effect of early infusion of abciximab on coronary patency before primary angioplasty in patients with acute myocardial infarction. BACKGROUND: Glycoprotein IIb/IIIa antagonists have proved to be effective in reducing ischemic events associated with coronary angioplasty. The present study explores whether abciximab alone, without administration of thrombolytic therapy, may induce reperfusion in patients with acute myocardial infarction. METHODS: In the Glycoprotein Receptor Antagonist Patency Evaluation pilot study 60 patients with less than 6 h signs and symptoms of acute myocardial infarction eligible for primary angioplasty received in the emergency room a bolus of abciximab 250 microg/kg followed by a 12-h infusion of 10 microg/min. All patients were also treated with an oral dose of 160 mg aspirin and 5,000 IU of heparin intravenously. As soon as possible a diagnostic angiography was performed to evaluate the patency of the infarct-related artery. RESULTS: The median time between onset of symptoms and the administration of the abciximab bolus was 150 min (range 45 to 345), and the median time between abciximab bolus and first contrast injection in the infarct-related artery was 45 min (range 10 to 150). In 24 patients (40%, 95% confidence interval 28% to 52%) Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at a median time of 45 min (range 10 to 150) after abciximab bolus; TIMI flow grade 3 was observed in 11 patients (18%, 95% confidence interval 9% to 28%). There was no difference in percentage of TIMI flow grade 2 or 3 between patients who received abciximab within 2.5 h after onset of symptoms or thereafter. CONCLUSIONS: Abciximab therapy given in the emergency room in patients awaiting primary angioplasty is associated with full reperfusion (TIMI flow grade 3) in about 20% and with TIMI flow grade 2 or 3 in about 40% of the patients at a median time of 45 min. These figures are higher than those in primary angioplasty trials without such pretreatment. Randomized controlled trials of very early infusion of abciximab, either prehospital or in-hospital, in patients eligible for angioplasty are warranted.     

Use of Abciximab in threatening vascular occlusion after PTCA

The administration of GP IIb/IIIa antagonists has been shown to be effective in reducing myocardial infarction and cardial death when given before PTCA. This prospective study was performed to determine the efficacy of abciximab in a bail-out situation to manage threatened or acute vessel closure. METHODS: Acute or threatened vessel closure was observed in 104 (5.5%) out of 1903 consecutive patients treated with PTCA in our institution. Of the 104 patients 46 (44%) were treated for unstable angina (CCS IV). Abciximab was administered in bail-out situations in a dosage of 0.25 mg/kg given as a bolus, which was followed by an intravenous infusion of 10 micrograms/min over 12 hours. Repeat PTCA was performed shortly after the administration of the abciximab bolus. After the procedure, the sheath was left in place and control angiography was carried out 24 h later. RESULTS: In 100 of the 104 patients TIMI flow III could be restored by abciximab therapy and RePTCA. In 4 patients an additional stent implantation was necessary due to persistent flow limitation. One day post PTCA, early follow-up angiography demonstrated patency of all vessels except two. In-hospital events occurred in 4 patients. Three of these patients underwent emergency CABG due to subacute vessel closure a few hours after PTCA and died during or directly after surgery. Follow-up after one year included clinical status and control angiography of the target vessel. During long-term follow-up, MACE occurred in 15 patients (2 MI, 8 CABG and 5 RePTCA). CONCLUSION: The results of this prospective trial demonstrate the efficacy of abciximab therapy in bail-out situations occurring during or early after PTCA. The use of abciximab in bail-out situations appears clinically beneficial. Further studies have to compare the efficacy of this approach with prophylactic abciximab treatment.     

Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial.

OBJECTIVES: We examined the utility of early percutaneous coronary intervention (PCI) in a trial that encouraged its use after thrombolysis and glycoprotein IIb/IIIa inhibition for acute myocardial infarction (MI). BACKGROUND: Early PCI has shown no benefit when performed early after thrombolysis alone. METHODS: We studied 323 patients (61%) who underwent PCI with planned initial angiography, at a median 63 min after reperfusion therapy began. A blinded core laboratory reviewed cineangiograms. Ischemic events, bleeding, angiographic results, and clinical outcomes were compared between early PCI and no-PCI patients (n = 162), between patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 before PCI versus flow grade 2 or 3, and among three treatment regimens. RESULTS: Early PCI patients showed a procedural success (<50% residual stenosis and TIMI flow grade 3) rate of 88% and a 30-day composite incidence of death, reinfarction, or urgent revascularization of 5.6%. These patients had fewer ischemic events and bleeding complications (15%) than did patients not undergoing early PCI (30%, p = 0.001). Early PCI was used more often in patients with initial TIMI flow grade 0 or 1 versus flow grade 2 or 3 (83% vs. 60%, p < 0.0001). Patients receiving abciximab with reduced-dose reteplase (5 U double bolus) showed an 86% incidence of TIMI grade 3 flow at approximately 90 min and a trend toward improved outcomes. CONCLUSIONS: In this analysis, early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective. This approach has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.     

Early administration of abciximab bolus in the emergency department improves angiographic outcome after primary PCI as assessed by TIMI frame count: results of the early ReoPro administration in myocardial infarction (ERAMI) trial.

OBJECTIVES: We assessed the safety and efficacy of early administration of abciximab prior to percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. BACKGROUND: Research suggests that platelet glycoprotein IIb/IIIa receptor inhibitors, e.g. abciximab, may improve myocardial perfusion. In particular, early administration in the emergency department, prior to PCI, may result in more effective reperfusion. METHODS: Eighty AMI patients with planned PCI were randomized in a double-blind fashion to receive a 0.25 mg/kg abciximab bolus either "early" in the emergency department or "late" in the catheterization laboratory after angiographic assessment. In total, 74 patients underwent PCI after diagnostic angiography, all of which then received an abciximab infusion of 0.125 microg/kg/min for 12 hr. RESULTS: Prior to PCI, no significant differences were observed between the two groups regarding the angiographic endpoints or ST-segment resolution. After PCI, thrombolysis in MI (TIMI) frame count (TFC) was significantly improved in patients treated early rather than in those treated late (23 +/- 10 vs. 41 +/- 35; P = 0.02). Consistent trends, also favoring early treatment, were observed for TIMI flow grade 3 (TFG 3), corrected TFC (CTFC), and TIMI myocardial perfusion grade 3 (TMPG 3). Nine deaths (4 early, 5 late) and six significant bleeds (4 early, 2 late) were observed at 30 days after randomization. CONCLUSIONS: Early administration of abciximab is both feasible and safe in patients planned for primary PCI, increasing coronary flow and myocardial reperfusion after PCI, as demonstrated by significantly decreased TFC scores and trends toward improvements in TFG, CTFC, and TMPG.     

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.     

阿昔单抗降低急性心肌梗死直接PTCA术缺血危险性的观察

目的　探讨血小板Ⅱb/Ⅲa受体拮抗剂阿昔单抗在急性心肌梗死直接经皮冠状动脉腔内成形术 (PTCA)术中应用的安全性 ,合理性和对PTCA术后缺血并发症及预后的影响。方法　对 6 0例胸痛小于 2h施行直接PTCA治疗的急性心肌梗死患者 ,随机分成对照组 30例和阿昔单抗组 30例 ,对照组静脉注射常规剂量肝素 10 0U/kg ,阿昔单抗组静脉注射小剂量肝素 70U/kg和阿昔单抗 0 .2 5mg/kg,随后以阿昔单抗 10 μg/min持续静脉滴注 12h ,观察 30d时两组死亡率、心肌梗死、再次急诊冠脉血运重建术和出血发生率。结果　随访 30d ,两组均未见出血并发症 ,对照组复合终点事件发生率为 10 %;阿昔单抗组无 1例死亡 ,也未发生心肌梗死和施行再次冠脉血运重建术。结论　在急性冠脉缺血综合征中 ,应用血小板Ⅱb/Ⅲa受体拮抗剂是安全合理的 ,血小板Ⅱb/Ⅲa受体拮抗剂阿昔单抗能降低急性心肌梗死患者直接PTCA术后缺血并发症 ,改善患者预后。     

Pre-hospitalization treatment with Abciximab in the preparation of patients for primary angioplasty in the acute phase of myocardial infarct. Immediate and long-term (one month) results

Percutaneous transluminal coronary angioplasty (PTCA) is an alternative to fibrinolysis in the treatment of acute myocardial infarction (AMI). However, after balloon PTCA, the rate of early re-occlusion, of re-infarctus and of restenosis remains high. Stent implantation with antiplatelet drug regimen (aspirin, ticlid) limits these risks. Abciximab (new GPIIb/IIIa receptors inhibitor) reduces PTCA complications rate in the acute coronary syndromes. Intravenous administration of abciximab can restore a normal flow in the infarcted related coronary artery (IRA) after few minutes. A monocentric, non randomized, prospective pilot study was iniated to assess the feasibility of pre-hospital treatment with abciximab in preparation to primary PTCA stenting in AMI (primary endpoint) and to appreciate potential benefits in initial IRA patency as well as prevention of PTCA thrombotic complications (secondary endpoint). Between April 1997 and January 1998, 38 AMI were treated with abciximab in pre-hospital phase (group A). Mobil Intensive Care Unit (MICU) team implemented the treatment and guaranteed immediate transport to the cathlab (abciximab bolus-coronary angiography time = 37 +/- 17 min). Immediate results were compared to those of 198 paired patients who were treated for AMI during the same period (Group T). Initial IRA flow TIMI grade 3 was significantly higher in group A, 24%, than in group T, 9% (p < 0.017). The rates of per-procedural complications (no flow, distal embolism), of local complications, of transfusions were not significantly different. During 1 month follow-up, there was no significant difference between group A and group T concerning death, re-MI, stent thrombosis and new revascularization. To conclude, the pre-hospital treatment with abciximab in AMI is feasible by MICU medical team without any delay of the cathlab admission. It is associated with no increased hemorrhagic complications rate. The abciximab pre-hospital treatment improves the initial IRA patency. These encouraging preliminary results expect to be confirmed by larger, multicentric, randomized and prospective studies.     

Initial experience in the management of myocardial infarction with primary angioplasty: results of the activity in two hospitals of the Turin area without on-site cardiac surgery]

BACKGROUND: Reperfusion therapy of ST-elevation myocardial infarction (STEMI) with primary coronary angioplasty (PTCA) is becoming an accepted therapeutical strategy because of a lower incidence of reinfarction, of hemorrhagic stroke and for a greater reduction of the infarct size in comparison to thrombolytic therapy. In this study we evaluated the feasibility and the effectiveness of such a strategy in two hospitals without on-site heart surgery but with a high volume of admission for acute coronary syndrome and a high caseload of elective interventional procedures. METHODS: Since January 2001 we started a program of primary PTCA for all STEMI patients presenting within 12 hours of symptom onset. An interventional team (physician, nurse and technician) were on call in a 24/7/365 fashion. Aspirin, heparin and abciximab were administered in the emergency room to all patients. Immediately after the procedure patients were given clopidogrel. RESULTS: Up to December 2003, 464 patients (mean age 63 +/- 12 years, 19.8% female) underwent primary PTCA. The symptom-emergency room interval was 3 +/- 3.9 hours, while the door-to-balloon time was 52.5 +/- 39.4 min. A TIMI 0-1 flow in the infarct-related artery was present in 55.8% of patients. Seventy patients (15.1%) presented with shock. In 430 patients (92.7%) a TIMI 3 flow was restored followed by a reduction in ST-segment elevation > 50% in 356 patients (76.7%). Total in-hospital mortality was 4.9% (23 out of 464 patients). The mortality of patients with shock was 31.4% (22 out of 70 patients). Two patients (0.4%) underwent emergency bypass. Four patients (0.8%) were electively referred to surgery prior to discharge in order to complete revascularization, which could not be obtained with further PTCA. The rate of major hemorrhagic complications was 0.8%. CONCLUSIONS: Primary PTCA for STEMI is a reperfusion strategy feasible and effective even in hospitals without on-site heart surgery, provided that a high volume of routine and emergency interventional procedures is maintained and when such a strategy is timely performed according to international guidelines.     

Early abciximab administration in acute myocardial infarction treated with primary coronary intervention

BACKGROUND: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion and clinical outcomes of patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. In this prospective randomized trial, we evaluated the impact of early abciximab administration on angiographic findings, myocardial salvage and left ventricular function. METHODS AND RESULTS: Fifty-five consecutive patients with first AMI, undergoing primary PCI, were randomized to abciximab administration either in the emergency room (early group: 27 patients) or in the catheterization laboratory after coronary angiography (late group: 28 patients). The primary outcome measures were initial Thrombolysis In Myocardial Infraction (TIMI) grade flow, corrected TIMI frame count and myocardial blush grade as well as salvage index and left ventricular function recovery as assessed by serial scintigraphic scans performed at admission, and 7 days and 1 month after PCI. Angiographic analysis showed a significant difference in initial TIMI grade 3 flow, corrected TIMI frame count and myocardial blush grade favouring early group. Moreover, salvage index and left ventricular function recovery were significantly greater in the early group (P=0.007; and P=0.043, respectively). CONCLUSIONS: In patients with AMI, treated with primary PCI, early abciximab administration improves myocardial salvage and left ventricular function recovery probably by starting early recanalization of the infarct-related artery.     

Efficacy of low-dose mutant tissue-type plasminogen activator followed by planned rescue percutaneous transluminal coronary angioplasty as reperfusion therapy for acute myocardial infarction

OBJECTIVES: The efficacy of injection of a low-dose mutant tissue-type plasminogen activator (mt-PA), monteplase, followed by planned rescue percutaneous transluminal coronary angioplasty (PTCA) was compared with that of primary PTCA. METHODS: A total of 164 patients with acute myocardial infarction within 12 hr from onset were randomly assigned to a treatment with 80 x 10(4) U bolus of monteplase (Group M) or no administration (Group P) by the envelope method, followed by immediate angiography with angioplasty in patients with Thombolysis in Myocardial Infarction (TIMI) flow grade 0, 1 or 2. RESULTS: There were no differences in baseline characteristics between the two groups. Initial angiography showed a higher reperfusion rate (TIMI 2 + 3: 21% + 38% vs 13% + 9%, p < 0.001) and the median time to TIMI 3 was shorter (63 vs 78 min, p < 0.005) in Group M than in Group P, but the final TIMI 3 rate was similar (93% vs 96%). Peak creatine kinase was lower, and predischarge left ventricular ejection fraction measured in 70% of all patients was higher (59 +/- 9% vs 54 +/- 14%, p = 0.02) in Group M than in Group P. Recurrent ischemia with ST elevation occurred in three patients in Group M, but death, re-acute myocardial infarction or stroke did not occur in either group and the rate of bleeding complication was similar (4.9% vs 3.7%). PTCA was performed less frequently in Group M, but medical expenses were comparable in both groups. CONCLUSIONS: Low-dose mt-PA followed by rescue PTCA is effective for early recanalization and preservation of left ventricular function without increases in bleeding complications or medical expenses. These results suggest that low-dose mt-PA should be given to all patients with acute myocardial infarction who are scheduled to undergo primary PTCA.     

“Rescue” Utilization of Abciximab for the Dissolution of Coronary Thrombus Developing as a Complication of Coronary Angioplasty

Objectives. This study sought to test the effect on thrombus score of the “rescue” utilization of the glycoprotein IIb/IIIa antagonist abciximab given to patients in whom intracoronary thrombus has developed as a complication after percutaneous transluminal coronary angioplasty (PTCA) and to determine its clinical utility.

Background. Abciximab is effective in the prevention of acute ischemic complications when given prophylactically to patients during high risk PTCA. However, its ability to therapeutically dissolve newly formed intracoronary thrombus occurring as a complication after PTCA is not known.

Methods. We performed an observational study in 29 consecutive patients who received abciximab (0.25 mg/kg body weight intravenous bolus, followed by a 12-h infusion at 10 μg/min) after attempted PTCA caused either the new development or further progression of thrombus. Angiograms were analyzed to determine thrombus score and Thrombolysis in Myocardial Infarction (TIMI) flow grade before and after abciximab. Procedural and clinical success and long-term outcome were also determined.

Results. Thrombus score decreased from 3.0 ± 0.9 (mean ± SD) to 0.86 ± 0.92 (p < 0.001), and TIMI flow grade increased from 2.5 ± 0.7 to 2.9 ± 0.3 (p = 0.008). No instances of distal embolization or no-reflow were noted. The procedural success (≤50% residual stenosis) rate was 97%. The clinical success (procedural success with no in-hospital myocardial infarction, bypass surgery or death) rate was 93%.

Conclusions. Dissolution of thrombus and restoration of TIMI grade 3 flow were readily achieved after administration of abciximab when delivered in a “rescue” manner after the development of thrombosis after PTCA. This novel use of abciximab will need to be validated in randomized trials.     

Efficacy of 100 mg of double-bolus alteplase in achieving complete perfusion in the treatment of acute myocardial infarction

Objectives. The purpose of this study was to assess the efficacy of 150 mg of aspirin plus 100 mg of alteplase, administered as two intravenous bolus injections of 50 mg each given 30 min apart, and followed by intravenous heparin, on infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3).Background. previous workers have shown in animals that reducing the duration of an infusion of recombinant tissue-type plasminogen activator increases the initial rate of thrombolysis, resulting in high early infarct-related coronary artery patenecy rates. The logical progression of this idea is bolus administration.Methods, Consecutive patients presenting up to 6 h from the onset of symptoms were recruited for the study. Angiography was performed at 60 and 90 min after the first bolus and between 19 to 48 h after study entry. Patients were followed up for 1 month.Results. At 60 min, angiography revealed infarct-related coronary artery patency of TIMI flow grade 3 in 55 (86%) of 64 patients (95% confidence interval [CI] 75% to 93%) and TIMI flow grade 2 or 3 in 58 (91%) of 64 patients (95% CI 81% to 97%). At 90 min, infarct-related artery patency of TIMI flow grade 3 was achieved in 74 (88%) of 84 patients (95% CI 79% to 94%) and TIMI flow grade 2 or 3 in 78 (93%) of 84 patients (95% CI 85% to 97%). Two patients (2.4%) had early angiographic reocclusion whereas 10 (11.9%) had late reinfarction. Bleeding episodes were mostly minor, and there was no cerebrovascular bleeding. Five patients (6.0%) died within 1 month of the acute myocardial infarction.Conclusions. In 84 patients with acute myocardial infarction, administration of 100 mg of double-bolus (2 × 50 mg) alteplase, aspirin and heparin is associated with remarkably high early infarct-related coronary artery patency rates (TIMI flow grade 3) of 86% and 88%, respectively, at 60 and 90 min.     

Emergency coronary angioplasty for acute myocardial infarction--factors affecting acute restenosis in catheterization laboratory and reocclusion during hospitalization.

A total of 107 consecutive patients with acute myocardial infarction underwent emergency coronary angioplasty (PTCA). Restoration of blood flow with TIMI grade III was established by emergency PTCA in 101 patients (94.4%). "Acute restenosis" was defined as a lesion that, when dilated to less than 50%, narrowed again to more than 75% luminar reduction 5 min after the balloon inflation. Acute restenosis occurred in 39 patients (39%). Multivariate analysis selected 3 factors associated significantly with an increased rate of acute restenosis: (1) dissection, (2) small balloon/artery diameter ratio and (3) low systolic blood pressure during PTCA. Reocclusion, which was defined as a total reobstruction of the lesion during hospitalization following emergency PTCA, was examined by predischarge coronary angiography. Acute restenosis correlated significantly with an increase in reocclusion rate. The incidence of documented reocclusion was 12%. Residual stenosis, multivessel disease and irregular dilation correlated significantly with an increased rate of reocclusion. The in-hospital and postdischarge mortalities were 5.6% and 2.1%, respectively. In summary, emergency PTCA produced a high angiographic success rate. Use of adequate balloon size and sufficient dilation correlated significantly with angiographic outcome in emergency PTCA. Patients with acute restenosis, high residual stenosis, irregular dilation, and multivessel disease would have a relatively high risk of reocclusion.     

Usefulness of coronary flow velocity measurement by transthoracic Doppler echocardiography in patients with acute coronary syndrome

OBJECTIVES: To evaluate the usefulness of left anterior descending coronary artery (LAD) flow measured by transthoracic Doppler echocardiography (TTDE) in patients with acute coronary syndrome. METHODS: Thirty consecutive patients with acute coronary syndrome in the LAD territory and unstable angina or non-ST-segment elevation myocardial infarction required decisions on the need for emergency coronary angiography. The diastolic peak flow velocity was measured in the distal segment of the LAD under guidance of color Doppler echocardiography in the emergency room. If LAD flow was not detected within 10 min, the coronary flow was judged as under the detection limit. The results of TTDE were compared with the Thrombolysis in Myocardial Infarction (TIMI) grade of LAD determined by coronary angiography, which was performed within 1 week (mean 2.5 +/- 1.5 days) in all patients. RESULTS: Coronary flow was not detected by TTDE in six patients who had TIMI grade 1 or 0. The diastolic peak flow velocity in 19 patients with TIMI 3 was higher than that in 5 patients with TIMI 2 (20.1 +/- 4.1 vs 10.9 +/- 2.3 cm/sec, p = 0.0001). A diastolic peak flow velocity of 14 cm/sec was the optimal cut-off value for the prediction of TIMI 3, with a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: Coronary flow velocity measured by TTDE closely reflected the TIMI grade. Coronary flow measurement by TTDE is useful to decide the treatment strategy for patients with acute coronary syndrome in the emergency room.     

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.     

Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial).

OBJECTIVES: This prospective randomized trial evaluates the impact of early abciximab administration on angiographic and left ventricular function parameters. BACKGROUND: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. METHODS: Two-hundred ten consecutive patients with first AMI undergoing primary PCI were randomized to abciximab administration either in the emergency room (early group: 105 patients) or in the catheterization laboratory, after coronary angiography (late group: 105 patients). Primary end points were initial Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and myocardial blush grade (MBG), as well as left ventricular function recovery as assessed by serial echocardiographic evaluations. RESULTS: Angiographic pre-PCI analysis showed a significantly better initial TIMI flow grade 3 (24% vs. 10%; p = 0.01), cTFC (78 +/- 30 frames vs. 92 +/- 21 frames; p = 0.001), and MBG 2 or 3 (15% vs. 6%; p = 0.02) favoring the early group. Consistently, post-PCI tissue perfusion parameters were significantly improved in the early group, as assessed by 60-min ST-segment reduction > or =70% (50% vs. 35%; p = 0.03) and MBG 2 or 3 (79% vs. 58%; p = 0.001). Left ventricular function recovery at 1 month was significantly greater in the early group (mean gain ejection fraction 8 +/- 7% vs. 6 +/- 7%, p = 0.02; mean gain wall motion score index 0.4 +/- 0.3 vs. 0.3 +/- 0.3, p = 0.03). CONCLUSIONS: In patients with AMI treated with primary PCI, early abciximab administration improves pre-PCI angiographic findings, post-PCI tissue perfusion, and 1-month left ventricular function recovery, possibly by starting early recanalization of the infarct-related artery.     

提前应用替罗非班对急性ST段抬高心肌梗死患者急诊介入治疗疗效的影响

目的通过随机对比分析,探讨急性ST段抬高心肌梗死(STEMI)患者急诊经皮冠状动脉介入治疗(PCI)时,提前应用血小板糖蛋白(GP)Ⅱb/Ⅲa受体拮抗剂替罗非班是否安全,以及能否进一步改善急诊PCI疗效。方法2005年4月至2006年4月,160例拟诊急性STEMI的患者接受急诊PCI时联合应用替罗非班,最终158例患者纳入研究,其中男性117例,女性41例,平均年龄58.8±25.2岁(36～78岁)。将患者随机分为两组,第一组共80例,在急诊冠状动脉造影结束后开始应用为常规使用组,第二组78例,在获取知情同意后在急诊室即开始应用者为早期使用组。比较两组间的基础临床状况、术前梗死相关血管前向血流情况,术后血流情况以及出血事件与近期心血管事件。结果两组基础临床情况差异无统计学意义,早期使用组提前39.8min应用替罗非班。早期组术前IRA前向血流达到TIMI2～3级的比率高于常规组(分别为39.7%和23.8%,P=0.040),其中达到TIMI3级的比率亦显著高于常规组(分别为23.1%和10.0%,P=0.032)。两组术后TIMI3级获得率,校正的TIMI计帧数和Blush3级获得率差异无统计学意义。两组近期主要心血管事件发生率、出血事件与血小板减少症发生率差异无统计学意义。结论急性STEMI患者急诊PCI前提前应用替罗非班是安全的,虽然术后造影结果和临床预后并没有明显改善,但是提前应用替罗非班可以提高PCI前的梗死相关血管前向血流。需要设计更大的样本量,更早的应用时机和合适的较大剂量提前应用替罗非班进一步深入研究。     

Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty.

AIM: To investigate the effect of abciximab on microvascular integrity and left ventricular (LV) functional recovery in patients with acute myocardial infarction (MI) treated by primary coronary angioplasty (PTCA). METHODS AND RESULTS: Thirty-one patients (27 males; age 39-76 years) with first, acute MI (<6 h after onset) were randomized to receive either abciximab+primary PTCA (n=17) or primary PTCA alone (n=14). Baseline characteristics of the two groups were similar. Myocardial reperfusion was studied shortly after PTCA by corrected TIMI frame count (cTFC) and intracoronary myocardial contrast echocardiography (MCE), after 48 h by intravenous MCE using intermittent, harmonic power Doppler, and after 1 month by intravenous MCE and 99 mTc-tetrofosmin SPECT. The patients treated with abciximab showed a shorter cTFC (23+/-4 vs 30+/-9 frames; P<0.05), a more preserved microvascular integrity shortly after PTCA (77% vs 55%; P<0.01), after 48 h (86% vs 50%; P<0.005) and at 1-month follow-up (86% vs 54% by MCE, P<0.001, and 68% vs 60% by SPECT, P<0.005) than patients treated with PTCA alone. Abciximab patients also showed a better recovery of LV function, as demonstrated by greater reduction in wall motion score index (1.4+/-0.3 vs 1.5+/-0.2; P<0.05) and increase in LV ejection fraction (53+/-7% vs 48+/-5%; P<0.001). CONCLUSIONS: Abciximab improves microvascular perfusion and LV functional recovery in primary PTCA.     

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.     

Use of anti-GP IIb-IIIa in acute thrombosis after intracoronary stent implantation

Acute occlusion of coronary stents still occurs in 0.5–2% of patients. The usefulness of GP IIb-IIIa receptor inhibitors has never been evaluated in this indication. After 1,454 stent implantations, acute occlusion occurred in 16 patients. Direct percutaneous transluminal coronary angioplasty (PTCA) was immediately performed. In eight patients, no recurrent thrombosis occurred during the 15 min following PTCA, and abciximab infusion was started after this period. In six patients, immediate recurrent thrombosis occurred in the stent. In these cases, an intravenous bolus of abciximab followed by a new inflation at low pressure was performed. Fifteen min after the bolus, stable TIMI 3 flow was restored in all six cases, and no thrombus or haziness remained. In two patients, a TIMI 0 flow persisted despite PTCA and the use of a bolus of abciximab. No recurrent ischemic symptoms were observed before hospital discharge. Abciximab in combination with balloon angioplasty can be used safely to control acute thrombosis after stent deployment. Cathet. Cardiovasc. Diagn. 43:105–107, 1998. © 1998 Wiley-Liss, Inc.