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.     

Facilitated primary coronary intervention with abciximab and very low dose of alteplase during off-hours compared with direct primary intervention during regular hours.

In patients with acute myocardial infarction (AMI), the off-hour presentation is one of the major determinants of door-to-balloon delay. Moreover, the nighttime presentation is associated with increased mortality after primary coronary intervention (PCI). The prompt starting of a therapy able to start recanalization of the infarct-related artery before intervention might improve the results of off-hour primary PCI. We compared the outcome of 212 consecutive patients with AMI undergoing either direct or facilitated PCI according to the hour of presentation. Patients arriving off-hours were pretreated with alteplase (20 mg) and abciximab and underwent facilitated PCI. Patients presenting on-hours underwent direct PCI. A basal Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 was observed in 1.0% of patients undergoing direct PCI and in 44% of patients undergoing facilitated PCI (P = 0.001). More patients starting PCI with a TIMI 3 flow achieved a postinterventional fast TIMI frame count (72.0% vs. 38.8% direct PCI group vs. 34.9% facilitated PCI group with basal TIMI 0-2; P = 0.001) and a TIMI perfusion grade 3 (66.0% vs. 38.8% direct PCI group vs. 39.7% facilitated PCI group with basal TIMI 0-2; P = 0.004). Preinterventional TIMI flow grade 3 was associated with a higher gain in left ventricular ejection fraction at 1 month (10.9% +/- 6.4% vs. 7.0% +/- 9.6% direct PCI group vs. 6.1% +/- 6.0% facilitated PCI group with basal TIMI 0-2; P = 0.005). No significant difference was observed in major bleedings, although there was a trend toward a higher risk in the facilitated PCI group. Patients in the facilitated PCI group achieving a basal TIMI 3 flow showed improved myocardial reperfusion and better left ventricular function recovery. Bleeding complications associated with combination therapy remained an important concern.     

Minimum salvaged myocardium after rescue percutaneous coronary intervention: quantification by cardiac magnetic resonance

Introduction and objectives

When fibrinolysis fails in patients with ST elevation myocardial infarction, they are referred for a rescue percutaneous coronary intervention (PCI). However, there is still no evidence of how much myocardium potentially at risk we can actually salvage after rescue PCI.

Methods

Fifty consecutive patients. Cardiac magnetic resonance was performed within 6 days. Myocardial necrosis was defined by the extent of abnormal late enhancement, myocardium at risk by extent of edema, and the amount of salvaged myocardium by the difference between myocardium at risk and myocardial necrosis. Finally, myocardial salvage index (MSI) resulted from the fraction (area-at-risk minus infarct-size)/area-at-risk.

Results

The mean time elapsed between pain onset and fibrinolitic agent administration was 176 ± 113 min; time lysis-rescue = PCI 209 ± 122 min; time pain onset-PCI = 390 ± 152 min. The area at risk was 37% ± 13% and infarct size 34.5% ± 13%. Salvaged myocardium was 3% ± 4% and MSI 9 ± 8. Salvaged myocardium and MSI were similar between patients with the artery open on arrival at the catheterization lab (Thrombolysis in Myocardial Infarction [TIMI] 3) and those with TIMI flow ≤2 (3.3% ± 3.6% and 8.2 ± 6.9 in TIMI 0-2 vs 3.0% ± 3.7% and 10.8 ± 10.9 in TIMI 3; P = .80 and 0.31, respectively). No significant difference was observed between patients who went through rescue PCI within a shorter time and those with longer delay times.

Conclusions

The myocardial salvage after rescue PCI quantified by cardiac magnetic resonance is very small. The long delay times between pain onset and the opening of the infarct-related artery with PCI are most probably the reason for such a minimal effect of rescue PCI.Full English text available from: www.revespcardiol.org     

Abciximab and early adjunctive percutaneous coronary intervention are associated with improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 Trial

BACKGROUND: Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. METHODS: ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. RESULTS: Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution (P =.008). CONCLUSIONS: A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy.     

High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention

OBJECTIVES: We investigated whether a higher serum erythropoietin (EPO) level in patients with acute myocardial infarction (MI) subjected to successful primary percutaneous coronary intervention (PCI) can predict a smaller infarct size determined by creatine kinase (CK) release. BACKGROUND: Erythropoietin has been shown to protect cardiomyocytes from ischemia-reperfusion injury in rodents. METHODS: We prospectively studied 101 patients with first MI who received successful primary PCI within 12 h from the onset of MI. Blood samples were collected to examine the serum EPO level after the primary PCI and within 24 h from the onset of MI. RESULTS: The peak CK level and cumulative CK release were significantly lower in the above-median EPO group than in the below-median EPO group. Thrombolysis In Myocardial Infarction (TIMI) grades and collateral grades before PCI, infarct-related coronary arteries, time to the successful reperfusion from the onset of MI, and serum creatinine levels were similar in the two EPO groups. A stepwise multiple regression analysis revealed that the absolute serum EPO level (mU/ml) as well as TIMI grades after PCI and preinfarction angina was an independent predictor for the cumulative CK release. CONCLUSIONS: These data suggest that a high endogenous EPO level can predict a smaller infarct size in patients with acute MI subjected to successful primary PCI. This might be attributed to the potentially protective effect of endogenous EPO against ischemia-reperfusion injury in humans.     

急性心肌梗死直接与联合冠状动脉入治疗的比较

目的比较尿激酶静脉溶栓联合冠状动脉(冠脉)介入治疗(PCI)术与直接PCI术对急性心肌梗死(AMI)的有效性和安全性。方法64例首次ST段抬高AMI(STelevationmyocarialinfarc-tion,STEMI)患者随机分为直接PCI组(直接PCI治疗)和联合PCI组(在尿激酶静脉溶栓基础上联合直接PCI治疗)。PCI术治疗前后行冠脉造影、心电图检查,观察梗死相关血管(IRA)前向血流,测定心肌梗死溶栓治疗临床试验(TIMI)血流、TIMI心肌灌注分级(TMPG),计算冠脉造影灌注积分(APS)和心电图ST段回落程度,评估心外膜血管和心肌灌注情况,对两组患者介入术前IRA通畅率、住院期间出血并发症、急性缺血事件发生率及出院前左心室功能进行比较。用线性回归分析评价ST段回落程度与APS的相关性。结果PCI术前联合PCI组冠脉再通率显著高于直接PCI组(68.8%比37.6%,P<0.05),其中完全再通率在两组间比较差异有统计学意义(46.9%比21.9%,P<0.05);联合PCI组心肌再灌注率显著高于直接PCI组(71.9%比37.4%,P<0.01),其中完全心肌再灌注率在两组间比较差异有统计学意义(46.9%比21.9%,P<0.05)。PCI术后两组IRA的TIMI血流3级比较差异无统计学意义(90.6%比87.5%,P>0.05),但比较TMPG差异有统计学意义(93.8%比75.0%,P<0.05),其中TMP3级有明显差异(65.6%比37.5%,P<0.05);联合PCI组APS10~12分(心肌完全再灌注)与直接PCI组比较差异有统计学意义(P<0.01)。介入治疗后出院前联合PCI组的LVEF值明显大于直接PCI组。联合PCI组ST段完全回落比例明显高于直接PCI组。线性回归分析评价ST段回落程度与APS之间有显著相关性(相关系数r=0.961,P<0.001),住院期间两组均无死亡病例、严重出血及急性缺血事件发生。结论联合PCI术较直接PCI术可获得更好的IRA开通、心肌组织和微循环灌注及心功能的明显改善。APS结合TIMI血流分级和TMPG可较好地完整评价心外膜血管和心肌灌注情况,并与心电图ST段回落程度有显著相关性。     

Aborted myocardial infarction in intracoronary compared with standard intravenous abciximab administration in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction

Backgound

Abciximab reduces major adverse cardiac events (MACEs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary (IC) abciximab bolus application might be more effective than a standard intravenous (IV) bolus. So far the occurrence of aborted MI, a new therapeutic target of effective treatment in STEMI, has not been evaluated in IC versus IV abciximab administration in STEMI patients undergoing primary PCI.

Methods

To investigate the extent of aborted MI, 154 patients undergoing primary PCI were randomized to either IC (n = 77) or IV (n = 77) bolus abciximab administration with subsequent 12-hour intravenous infusion. For assessment of infarct size and extent of microvascular obstruction, all patients underwent late enhancement magnetic resonance imaging (MRI). Aborted MI was defined by major (≥ 50%) ST-segment resolution and a lack of subsequent cardiac enzyme rise ≥ 2 the upper normal limit. We also assessed the occurrence of true aborted MI defined as the absence of myocardial necrosis in MRI.

Results

The incidence of aborted MI was significantly higher in the IC group (p = 0.04); true aborted MI was only observed in the IC abciximab group (p = 0.01). At multivariable logistic regression analysis, IC abciximab application was a significant independent predictor of true aborted MI (p = 0.03). Aborted MI patients had an excellent prognosis at 6-month follow-up with no MACE as compared to 24 events in patients with non-aborted MI.

Conclusions

IC bolus application of abciximab in STEMI patients undergoing primary PCI results in a higher incidence of aborted MI and subsequent improved clinical outcome.     

Angiographic and clinical characteristics associated with the development of Q-wave and non-Q-wave myocardial infarction in the thrombolysis in myocardial infarction (TIMI) 14 trial

Background

In the absence of thrombolytic therapy, patients with non-Q-wave myocardial infarction (MI) have previously been shown to have lower long-term mortality rates than patients with Q-wave MI. The goal of our study was to examine the angiographic and clinical differences between non-Q-wave MI and Q-wave MI in patients with ST elevation MI (STEMI) in the era of thrombolytic and combination therapy of thrombolytics plus glycoprotein IIb/IIIa inhibitors.

Methods

Angiography was performed 90 minutes after thrombolytic administration in the Thrombolysis in Myocardial Infarction (TIMI) 14 trial. The development of a non-Q-wave MI was assessed on electrocardiogram performed at the time of hospital discharge. Angiographic findings were assessed at an angiographic core laboratory by blinded investigators.

Results

The qualifying episode of ST elevation developed into a non-Q-wave MI in 36% of patients (315/878) and into a Q-wave MI in 64% of patients (563/878). In patients in whom non-Q-wave MI developed, the rate of TIMI grade 3 flow was higher, peak creatine kinase level was lower, mean left ventricular ejection fraction was greater, corrected TIMI frame counts (CTFCs) were lower (ie, faster blood flow), and chest pain duration after thrombolytic administration was shorter. Patients in whom non-Q-wave MI developed less frequently underwent a percutaneous coronary intervention (PCI), and when they did, they had faster post-PCI CTFCs and higher rates of post-PCI TIMI grade 3 flow. Patients in whom a non-Q-wave MI developed had lower rates of severe recurrent ischemia. There were no differences in 30-day or in-hospital mortality rates or recurrent MI between patients with Q-wave MI and patients with non-Q-wave MI.

Conclusion

After thrombolytic therapy in STEMI with or without abciximab, ejection fractions were higher, the duration of ischemia was shorter, and coronary blood flow at both 90 minutes and after PCI was faster in patients who sustained non-Q-wave MI than in patients who sustained Q-wave MI. No differences in mortality or recurrent MI rates were detected in patients who sustained a Q-wave MI and patients in whom a Q-wave MI did not evolve in the modern thrombolytic era.     

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.     

Bleeding events with abciximab in acute coronary syndromes without early revascularization: An analysis of GUSTO IV-ACS

Background

The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates.

Methods

In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure.

Results

In 1507 patients (19.3%), bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) classification was observed while they were hospitalized or within 7 days. Ninety-eight patients (1.2%) had a major bleed, including 8 with intracranial hemorrhages. In 215 patients (2.8%), a minor bleed was reported, and in 1194 patients (15.3%), an insignificant bleed was reported. Bleeding was more frequent in patients receiving a 48-hour infusion of abciximab. Spontaneous bleeding was seen in 911 patients (11.7%). The other 596 patients had a bleeding event in conjunction with a procedure. The most significant predictors for bleeding with multivariable analysis were: use of low-molecular weight heparin, duration of abciximab infusion, region of hospitalization, performance of coronary artery bypass grafting or percutaneous coronary intervention (PCI), advanced age, and female sex. For major bleeding, the predictors were performance of coronary artery bypass grafting or PCI, long duration of abciximab administration, and advanced age.

Conclusion

Treatment with abciximab in patients with non-ST-elevation acute coronary syndromes is safe because major bleeding and stroke are rare, and most events are clinically manageable or have few clinical consequences. Guidelines for use of abciximab in combination with other antithrombotic agents developed for PCI should also be respected in acute coronary syndromes. Specific dosing guidelines for combination with low-molecular weight heparin must be developed for patients who subsequently will undergo a PCI.     

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.     

Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction

Background

Both epicardial and myocardial perfusion have been associated with clinical outcomes in the setting of ST elevation myocardial infarction (STEMI), and the performance of adjunctive/rescue percutaneous coronary intervention (PCI) may further improve clinical outcomes after fibrinolytic administration.

Methods

The goal was to develop a simple, broadly applicable angiographic metric that takes into account indices of epicardial and myocardial perfusion both before and after PCI to arrive at a single perfusion grade in patients undergoing cardiac catheterization after fibrinolysis. The angiographic perfusion score (APS) is the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG; 0-3) added to the TIMI myocardial perfusion grade (TMPG; 0-3) before and after PCI (total possible grade, 0-12). Failed perfusion was defined as an APS of 0 to 3, partial perfusion was defined as an APS of 4 to 9, and full perfusion was defined as an APS of 10 to 12. The APS was evaluated in patients from the Double-blind, Placebo-contolled, Multicenter Angiographic Trial of Rhumab CD18 in Acute Myocardial Infarction (LIMIT-AMI; n = 394) and Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis In Myocardial Infarction (ENTIRE-TIMI) 23 trials (n = 483), and infarct size (120-216 hours after AMI SPECT Technetium-99m Sestamibi data) was assessed in the LIMIT-AMI trial.

Results

The APS was associated with the incidence of death or myocardial infarction (failed, 16.7% [n = 18]; partial, 2.5% [n = 155]; full, 2.4% [n = 82]; P = .039 for trend) and larger SPECT infarct sizes (failed, median 39% [n = 10]; partial, 12% [n = 79]; and full, 8% [n = 35]; P = .002). No patient with full APS died, whereas the mortality rate was 11.1% in patients with a failed APS (P = .03).

Conclusions

The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI. Partial or full angiographic perfusion scores are associated with a halving of infarct size, and no patients with full angiographic perfusion died.     

Combined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI)

Background

Most patients with acute myocardial infarction (AMI) are admitted to hospitals without percutaneous transluminal coronary angioplasty (PTCA) facilities or are initially managed in a prehospital mobile unit. Thrombolysis remains the most readily available reperfusion treatment in those settings, but the optimal subsequent strategy in those patients is unclear. If a mechanical recanalization is likely to be performed in an emergency, it is probably desirable that the patient receives abciximab, the glycoprotein IIb/IIIa antagonist with the strongest evidence of benefit for angioplasty in AMI.

Objective

The aim of this trial is to compare the effects on clinical outcome and cost-effectiveness of 2 strategies after immediate treatment with abciximab and half-dose reteplase for ST-elevation AMI: to manage the patients conservatively (referring them for rescue PTCA only if needed) or to immediately send all patients for emergency coronary angioplasty.

Methods

The Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) is an open, prospective, randomized, multicenter clinical trial conducted in patients with high-risk ST-segment elevation AMI treated within 12 hours from symptom onset in hospitals without PTCA facilities or in a prehospital mobile intensive care unit. Apart from contraindications to thrombolysis, the main exclusion criteria are age ≥75 years and a past history of CABG surgery or a percutaneous coronary intervention procedure involving the infarct-related artery. Enrollment will be performed in hospitals without PTCA facilities or directly in the ambulance if a dedicated system is in place for prehospital diagnosis and treatment of AMI. Patients will receive half-dose reteplase and full-dose abciximab and will subsequently be randomized to conventional medical therapy (with referral for emergency rescue PTCA allowed in selected cases) or emergency angioplasty. The primary end point is the 30-day combined incidence of mortality, reinfarction, and refractory ischemia. In order to obtain a 95% power (2-sided) to detect a 42% reduction in the primary end point, 900 patients are required in each arm of the study. Secondary end points include the 1-year composite end point of mortality, reinfarction, refractory ischemia, and hospital readmission because of heart failure; resource use at 30 days and 1 year; and the incidence of inhospital stroke and bleeding complications in the 2 groups.

Results

Seventy-four patients have been randomized (as of March 10, 2004); results are expected in June 2005.

Conclusion

This study will establish whether angioplasty must be started as soon as possible in all patients who receive combined pharmacologic reperfusion with the glycoprotein IIb/IIIa inhibitor abciximab and half-dose thrombolysis or whether it can be postponed or skipped in patients with signs of successful reperfusion, with obvious organizational advantages.     

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.     

Routine pretreatment with abciximab versus standard periprocedural therapy in mechanically ventilated cardiogenic shock patients undergoing primary percutaneous coronary intervention: Subanalysis of the PRAGUE-7 study

BACKGROUND:

The clinical outcome of patients with myocardial infarction (MI) complicated by cardiogenic shock (CS) who require mechanical ventilation (MV) is poor.

OBJECTIVE:

To analyze the impact of abciximab pretreatment in this high-risk population of MI patients.

METHODS:

The present study was a retrospective subanalysis of the multicentre randomized Routine Upfront Abciximab Versus Standard Peri-Procedural Therapy in Patients Undergoing Percutaneous Coronary Intervention for Cardiogenic Shock (PRAGUE-7) study, which included 80 MI patients in CS undergoing primary percutaneous coronary intervention (PCI). Patients were randomly assigned into group A (routine pretreatment with an abciximab bolus followed by a 1 h abciximab infusion) and group B (standard therapy). The subanalysis included 37 patients requiring MV. Seventeen patients were in group A and 20 were in group B. The primary end point (death/stroke/reinfarction/new severe renal failure) at 30 days, procedural success (thrombosis in myocardial infarction [TIMI] flow) and frequency of bleeding were assessed. The χ² and Student’s t tests were used for statistical analysis; P<0.05 was considered to be statistically significant.

RESULTS:

The primary end point occurred in nine (53%) patients in group A and 12 (60%) patients in group B (P=0.66). TIMI flow after primary PCI was higher in group A (2.75 versus 2.31; P<0.05). Major bleeding occurred in 12% of patients in group A versus 10% of patients in group B (P=0.86). Minor or minimal bleeding was more common in group A (29%) compared with group B (5%; P<0.05).

CONCLUSION:

The results of the present study suggest that routine pretreatment with abciximab before primary PCI in mechanically ventilated patients with MI complicated by cardiogenic shock was associated with better angiographic results but also with a higher incidence of bleeding.     

Short- and long-term recovery of left ventricular function predicted at the time of primary percutaneous coronary intervention in anterior myocardial infarction

OBJECTIVES: The aim of this study was to determine predictors of left ventricular (LV) function recovery at the time of primary percutaneous coronary intervention (PCI). BACKGROUND: Angiographic, intracoronary Doppler flow, and electrocardiographic variables have been reported to be predictors of recovery of LV function after acute myocardial infarction (MI). We directly compared the predictive value of Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (cTfc), myocardial blush grade, coronary Doppler flow velocity analysis, and resolution of ST-segment elevation for recovery of LV function in patients undergoing primary PCI for acute MI. METHODS: We prospectively studied 73 patients who underwent PCI for an acute anterior MI. Recovery of global and regional LV function was measured using an echocardiographic 16-segment wall motion index (WMI) before PCI, at 24 h, at one week, and at six months. Directly after successful PCI, coronary flow velocity reserve (CFR), cTfc, TIMI flow grade, and myocardial blush grade were assessed. RESULTS: Mean global and regional WMI improved gradually over time from 1.86 +/- 0.23 before PCI to 1.54 +/- 0.34 at six-month follow-up (p < 0.0001) and from 2.39 +/- 0.30 before PCI to 1.87 +/- 0.48 at six-month follow-up (p < 0.0001), respectively. Multivariate analysis revealed CFR as the only independent predictor for global and regional recovery of LV function at six months. CONCLUSIONS: Doppler-derived CFR is a better prognostic marker for LV function recovery after anterior MI than other currently used parameters of myocardial reperfusion.     

The level I cardiovascular center: is it time?

There is no uniform approach to treating the 1.5 million US citizens who have an acute myocardial infarction (AMI) each year. This contrasts with the trauma system developed to efficiently triage and treat the critically injured accident victim. Only two thirds of patients with ST-segment elevation AMI in the United States are treated with thrombolytic therapy or primary angioplasty (percutaneous coronary intervention [PCI]) which can reduce the 30-day mortality rate from approximately 15% to 6%-10%. The Early Retavase-Thrombolysis in Myocardial Infarction (ER-TIMI) 19 trial demonstrated that AMI patients who received prehospital thrombolytic therapy and were brought to the nearest receiving hospital experienced a 32-minute reduction in the time to treatment and time to ST-elevation resolution compared with those treated at their time of hospital arrival. This expedited therapy was associated with a low in hospital mortality rate (4.7%). The potential benefit of facilitated PCI with partial-dose thrombolysis and abciximab administration was demonstrated by the Strategies for Patency Enhancement in the Emergency Department (SPEED) investigators who found that double bolus recombinant plasminogen activator (reteplase) (5 + 5 megaunits) and abciximab with the addition of early PCI, resulted in a final infarct-related artery TIMI 3 flow rate of 86% compared with 77% with combination therapy alone. The Primary Angioplasty in Acute Myocardial Infarction (PAMI) investigators have shown that patients admitted with infarct-related artery TIMI 3 flow at the time of primary PCI had less than a 1% 6-month mortality. Treating AMI patients with prehospital, partial dose thrombolysis followed by immediate transport to a Level I cardiovascular center (bypassing the closest hospital if necessary) for facilitated infarct-related artery PCI has the potential to reduce the mortality in ST-elevation AMI patients from 6%-10% to less than 4% which could translate into saving approximately 500 lives per day in the United States. It is time to validate this strategy with a randomized clinical trial, the Prehospital Administration of Thrombolytic Therapy With Urgent Culprit Artery Revascularization trial (PATCAR).     

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.     

Predictors of in-hospital outcome after primary percutaneous coronary intervention for recurrent myocardial infarction

BACKGROUND: Recurrent acute myocardial infarction (AMI) is a deteriorated condition with high in-hospital morbidity and mortality, but the predictors of in-hospital outcome after primary percutaneous coronary intervention (PCI) for repeat AMI remain unclear. METHODS AND RESULTS: Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings, results of primary PCI, and in-hospital prognosis were retrospectively compared between primary PCI-treated AMI patients with previous myocardial infarction (MI) (repeat-MI patients, n=235) and those without previous MI (first-MI patients, n=1,550). The repeat-MI patients had higher prevalence of Killip class>or=3 at admission, larger number of diseased vessels, and a significantly higher in-hospital mortality rate than the first-MI patients. On multivariate analysis, number of diseased vessels>or=2 or diseased left main trunk (LMT) on initial coronary angiography was the independent positive predictor of in-hospital mortality in the repeat-MI patients, not in the first-MI patients, whereas acquisition of Thrombolysis In Myocardial Infarction 3 flow in the infarct-related artery immediately after primary PCI and elapsed time<24 h were the negative predictors in the first-MI patients, not in the repeat-MI patients. CONCLUSIONS: Number of diseased vessels>or=2 or diseased LMT on initial coronary angiography is an independent risk factor of in-hospital death in recurrent-AMI patients undergoing primary PCI.     

Preliminary experience with drug-coated balloon angioplasty in primary percutaneous coronary intervention

We evaluated the clinical feasibility of using drug-coated balloon (DCB) angioplasty in patients undergoing primary percutaneous coronary intervention (PPCI). Between January 2010 to September 2014, 89 ST-elevation myocardial infarction patients (83% male, mean age 59 ± 14 years) with a total of 89 coronary lesions were treated with DCB during PPCI. Clinical outcomes are reported at 30 d follow-up. Left anterior descending artery was the most common target vessel for PCI (37%). Twenty-eight percent of the patients had underlying diabetes mellitus. Mean left ventricular ejection fraction was 44% ± 11%. DCB-only PCI was the predominant approach (96%) with the remaining 4% of patients receiving bail-out stenting. Thrombolysis in Myocardial Infarction (TIMI) 3 flow was successfully restored in 98% of patients. An average of 1.2 ± 0.5 DCB were used per patient, with mean DCB diameter of 2.6 ± 0.5 mm and average length of 23.2 ± 10.2 mm. At 30-d follow-up, there were 4 deaths (4.5%). No patients experienced abrupt closure of the infarct-related artery and there was no reported target-lesion failure. Our preliminary experience showed that DCB angioplasty in PPCI was feasible and associated with a high rate of TIMI 3 flow and low 30-d ischaemic event.