Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial)

doi:10.1016/S0002-9149(99)00437-3

The American Journal of Cardiology

Volume 84, Issue 7, 1 October 1999, Pages 779-784

https://doi.org/10.1016/S0002-9149(99)00437-3 Get rights and content

Abstract

We evaluated the effects of abciximab treatment during early angioplasty after clinically failed thrombolysis for acute myocardial infarction. In the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial of reteplase versus alteplase for acute infarction (n = 15,059), 392 patients underwent angioplasty a median of 3.5 hours after thrombolysis and had complete procedural data. We compared 30-day mortality and in-hospital outcomes between patients who received abciximab (n = 83) and those who did not (n = 309), and (among patients given abciximab) between those randomized to alteplase versus reteplase. Patients given abciximab had anterior infarction less often, but were more often in Killip classes III or IV. The 30-day mortality rate tended to be lower with abciximab (3.6% vs 9.7%, p = 0.076), more so after adjustment for baseline differences (p = 0.042). The composite of death, stroke, or reinfarction did not differ significantly with abciximab treatment (12% vs 14%, p = 0.7), but it occurred less often among abciximab-treated patients who had been randomized to reteplase (n = 55) versus alteplase (n = 28) (7% vs 21%, p = 0.08). Severe bleeding was increased among abciximab-treated patients (3.6% vs 1.0%, p = 0.08), despite less heparin use. No intracranial hemorrhages occurred with abciximab. The use of abciximab for early angioplasty after clinically failed thrombolysis resulted in trends toward lower 30-day mortality and increased bleeding.

Section snippets

Study design

This was a prospectively designed analysis of a subgroup of patients in the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial who underwent early PTCA.8 In brief, patients of any age who had ST-segment elevation ≥1 mm in 2 consecutive limb leads or ≥2 mm in 2 precordial leads, or bundle branch block <6 hours after symptom onset were eligible. Patients were excluded from GUSTO-III for factors related to bleeding or stroke risk. Patients were randomized in a 2:1 ratio

Results

Baseline characteristics and outcomes (death, stroke, reinfarction) of early PTCA patients in the analysis did not differ significantly from those of early PTCA patients who were not analyzed (Table I), except for the incidence of diabetes (15% vs. 22%) and United States enrollment (82% vs. 56%).

Discussion

Our analysis of patients with AMI undergoing early PTCA (within 24 hours of thrombolysis) in the GUSTO-III trial supports the concept that concomitant abciximab may offer substantial benefit to these patients. In most studies, patients undergoing “rescue” PTCA after failed thrombolysis have had higher mortality than patients with successful reperfusion.1, 4 In this study, abciximab given during early PTCA after clinically failed thrombolysis was associated with a trend toward lower 30-day

References (13)

C.H Davies et al.
Failed coronary thrombolysis
Lancet
(1998)
J Lefkovits et al.
Effects of platelet glycoprotein IIb/IIIa receptor blockade by a chimeric monoclonal antibody (abcix-imab) on acute and six-month outcomes after percutaneous transluminal coronary angioplasty for acute myocardial infarction
Am J Cardiol
(1996)
S.G Ellis et al.
Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction
Circulation
(1994)
E.M Ohman et al.
Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction
Circulation
(1990)
R.M Califf et al.
Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator failsresults of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial
Circulation
(1988)
Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty
Circulation
(1997)

There are more references available in the full text version of this article.

Cited by (84)

One-year clinical outcome of patients treated with or without abciximab in rescue coronary angioplasty
2013, International Journal of Cardiology
Citation Excerpt :
We found a low incidence of major bleedings and vascular complications without significant differences in between the groups treated with or without abciximab. These findings are consistent with some authors [12] but in conflict with others who report a trend [11] or a significant increase [20] in major bleedings in patients treated with abciximab. The lower risk of bleedings and vascular complications observed in our population is in line with recent findings [21] and is probably related to a wide use of radial approach, weight adjusted heparin doses, smaller sheath size.
The clinical results of abciximab administration during rescue angioplasty (PCI) are poorly investigated.
We evaluated the outcome of 406 consecutive patients undergoing rescue PCI treated with (n = 218) or without (n = 188) abciximab and a clopidogrel loading dose of 300 mg. The end point was the incidence of major cardiac adverse events (MACE) defined as death, recurrent acute myocardial infarction (AMI) and target vessel revascularization at 30 days and 1 year. The predictors of MACE were also investigated.
No differences were found in MACE between the groups treated with or without abciximab at 30 days (15 and 20, p = 0.67) and 1 year (23 and 29, p = 0.85). Stepwise logistic regression analysis identified: cardiogenic shock (Odds Ratio [OR] = 17.8, 95% confidence interval [CI] 5–99, p = 0.0001), age (OR = 1.099, 95% CI 1.04–1.15, p = 0.0001), TIMI flow 0–1 after procedure (OR = 5.51, 95% CI 1.72–17.6, p = 0.004) as independent predictors of MACE at 30 days. Cox proportional hazards model identified: cardiogenic shock (adjusted hazard ratio [HR] = 3.83, 95% confidence interval [CI] 1.76–8.35, p = 0.01), age (HR = 3.7, 95% CI 1.75–8.3, p = 0.01), TIMI flow 0–1 after procedure (HR = 1.04, 95% CI 1.01–1.07, p = 0.001 as predictors of MACE at 1 year). After propensity score adjustments the predictors of MACE did not change.
There were no differences in MACE at 30 days and 1 year in patients treated with or without abciximab during rescue PCI after a clopidogrel loading dose of 300 mg. Cardiogenic shock, age and TIMI flow 0 and 1 after PCI were predictors of MACE.
Safety and efficacy of rescue angioplasty for ST-elevation myocardial infarction with high utilization rates of glycoprotein IIb/IIIa inhibitors
2012, American Heart Journal
Fibrinolytic therapies remain widely used for ST-elevation myocardial infarction, and for “failed reperfusion,” rescue percutaneous coronary intervention (PCI) is guideline recommended to improve outcomes. However, these recommendations are based on data from an earlier era of pharmacotherapy and procedural techniques.
To determine factors affecting prognosis after rescue PCI, we studied 241 consecutive patients (median age 55 years, interquartile range [IQR] 48-65) undergoing procedures between 2001 and 2009 (53% anterior ST-elevation myocardial infarction and 78% transferred). The median treatment-related times were 1.2 hours (IQR 0.8-2.2) from symptom onset to door, 2 hours (IQR 1.3-3.2) from symptom onset to fibrinolysis (93% tenecteplase), and 3.9 hours (IQR 3.1-5.2) from fibrinolysis to balloon. Procedural characteristics were stent deployment in 95% (11.6% drug eluting) and 78% glycoprotein IIb/IIIa inhibitor use, and Thrombolysis In Myocardial Infarction (TIMI) 3 flow rates pre-PCI and post-PCI were 41% and 91%, respectively (P < .001). At 30 days, TIMI major bleeding occurred in 16 (6.6%) patients, and 23 (9.5%) patients received transfusions; nonfatal stroke occurred in 4 (1.7%) patients (2 hemorrhagic). Predictors of TIMI major bleeding were female gender (odds ratio 3.194, 95% CI 1.063-9.597; P = .039) and pre-PCI shock (odds ratio 3.619, 95% CI,1.073-12.207; P = .038). Mortality at 30 days was 6.2%, and 3.2% in patients without pre-PCI shock. One-year mortality was 8.2% (5.3% in patients without pre-PCI cardiogenic shock), 5.2% had reinfarction, and the target vessel revascularization rate was 6.4% (2.6% in arteries ≥3.5 mm in diameter). Pre-PCI shock, female gender, and post-PCI TIMI flow grades ≤2 were significant predictors of 1-year mortality on multivariable regression modeling, but TIMI major bleeding was not.
Rescue PCI with contemporary treatments can achieve mortality rates similar to rates for contemporary primary PCI in patients without pre-PCI shock. Whether rates of bleeding can be reduced by different pharmacotherapies and interventional techniques needs clarification in future studies.
Survival of patients undergoing rescue percutaneous coronary intervention
2011, JACC: Cardiovascular Interventions
This study sought to develop a tool for predicting an individual's risk of mortality following rescue percutaneous coronary intervention (PCI).
Although fibrinolytic therapy is appropriate and improves survival for certain ST-segment elevation myocardial infarction patients, a substantial proportion suffer ongoing myocardial ischemia, a class I indication for emergent percutaneous coronary intervention (rescue PCI).
Using the National Cardiovascular Data Registry (NCDR), rescue PCI was defined as nonelective PCI following failed fibrinolysis in patients with continuing or recurrent myocardial ischemia. Multivariable logistic regression was used to determine mortality predictors and the C-statistic for model discrimination. The NCDR-RESCUE (Real-World Estimator of Survival in Catheterized STEMI Patients Following Unsuccessful Earlier Fibrinolysis) score was developed using a shortened list of 6 pre-angiographic variables and 70% of the cohort; performance was subsequently validated against the remaining 30%.
Among 166,516 PCI procedures on patients with an admission diagnosis of ST-segment elevation myocardial infarction, 8,007 (4.8%) represented rescue PCI. In-hospital mortality occurred in 464 (5.8%). Factors in the final model were age, glomerular filtration rate, history of congestive heart failure, insulin-treated diabetes, cardiogenic shock, and salvage status. The NCDR-RESCUE score effectively segregated individuals into 6 clinically meaningful risk categories, with 0.4% (0.0% to 1.3%), 1.6% (0.9% to 2.4%), 7.6% (5.3% to10.4%), 27.5% (20.7% to 35.1%), 64.2% (49.8% to 76.9%), or 100% (59.0% to 100.0%) risk, respectively, of in-hospital mortality (mean ± 95% confidence interval, C-index = 0.88, Hosmer-Lemeshow p = 0.898).
In-hospital mortality risk among individuals undergoing rescue PCI varies from minimal to extreme and can be easily calculated using the NCDR-RESCUE score. This information can be of value in counseling patients, families, and referring caregivers.
Management of failed thrombolysis after acute myocardial infarction: An overview of current treatment options
2007, International Journal of Cardiology
Thrombolytic therapy remains the most commonly administered revascularization strategy for patients with ST-elevation myocardial infarctions (STEMI). However, many patients fail to have patent arteries or ST-segment resolution after these therapies. Multiple strategies have been examined to treat these patients with “failed thrombolysis.” We examined the existing medical literature regarding treatment of failed thrombolysis including strategies testing repeat thrombolytic therapy and rescue percutaneous coronary intervention. Additional, we reviewed the literature regarding the efficacy of transferring patient for rescue percutaneous intervention and coronary stenting. The impact of contemporary antiplatelet strategies, cardiogenic shock, and coronary bypass surgery was examined. Overall, the management of patients with acute STEMI in whom thrombolytic therapy failed remains a challenging problem. As a result, many different strategies are currently in use. Among these therapeutic interventions, rescue PCI with coronary stenting appears to be superior when it is done in a timely manner by an experienced center.
Soluble CD40 ligand:interleukin-10 ratio predicts in-hospital adverse events in patients with ST-segment elevation myocardial infarction
2007, Thrombosis Research
The balance between pro-inflammatory and anti-inflammatory molecules is likely to modulate the processes that lead to atherogenesis and rapid coronary artery disease progression. We sought to compare the positive predictive values of serum soluble CD40 ligand (sCD40L)/interleukin-10 (IL-10) ratio, versus individual sCD40L, and IL-10 measurements regarding in-hospital events in patients admitted into the hospital with ST-segment elevation myocardial infarction (STEMI).
We recruited 96 patients with STEMI. sCD40L and IL-10 were measured at hospital admission in every patient. The composite of in-hospital death and heart failure represented the study end-point. Heart failure was defined as Killip class > 1. Multivariable logistic regression analysis was performed to identify independent variables related to in-hospital events.
Thirty two patients (33%) achieved the study end-point and 64 (67%) had no adverse events during hospital admission. IL-10 levels (pg/ml) were lower (28.2 ± 9.8 versus 33.24 ± 11.3, p = 0.03) and sCD40L levels (pg/ml) higher (156.8 ± 54.2 versus 135.4 ± 38.70, p = 0.02) in patients with events compared to those without events. Significantly higher odd ratios were found for sCD40L/IL-10 ratio (OR = 2.10, 95% CI: 1.90 to 2.80, p = 0.01) compared to individual sCD40L (OR = 1.40, 95% CI: 0.90 to 2.20, p = 0.08) and IL-10 (OR = 0.70, 95% CI: 0.50 to 0.93, p = 0.02) measurements.
Our study showed that serum ratio of sCD40L/IL-10 is a better independent predictor of in-hospital adverse events than individual sCD40L and IL-10 measurements in patients with STEMI.
A Meta-Analysis of Randomized Trials of Rescue Percutaneous Coronary Intervention After Failed Fibrinolysis
2006, American Journal of Cardiology
Previous trials have suggested clinical benefit with rescue percutaneous coronary intervention (PCI) after failed fibrinolysis, but more recent, larger studies are conflicting. Therefore, we designed a meta-analysis to determine whether rescue PCI improves outcomes compared with conservative therapy in the setting of early failure of fibrinolysis. We searched MEDLINE for randomized trials by using the Medical Subject Heading terms “angioplasty,” “myocardial infarction,” “thrombolytic therapy,” and “fibrinolysis.” The inclusion criteria were (1) acute ST-elevation myocardial infarction initially treated with fibrinolytics, (2) randomization of patients with failed fibrinolysis to immediate PCI or conservative therapy, and (3) available short-term clinical outcome data. The primary end point was short-term mortality and secondary end points were thromboembolic stroke and heart failure. Numbers of events were tabulated for each trial and risk ratios (RRs) were computed. Five trials were included for analysis. The pooled RR estimates showed a 36% decrease in the risk of death in the rescue arm (RR 0.64, 95% confidence interval 0.41 to 1.00, p = 0.048) and a marginally significant 28% decrease in the risk of heart failure (RR 0.72, 95% confidence interval 0.51 to 1.01, p = 0.06). We also found a marginally increased risk of thromboembolic stroke in the rescue arm (RR 3.61, 95% confidence interval 0.91 to 14.27, p = 0.07). In conclusion, rescue PCI in the setting of early fibrinolytic failure improves mortality, but this is tempered by a possible increase in the risk of thromboembolic stroke.

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^☆: The GUSTO-III trial was funded by a grant from Boehringer-Mannheim Therapeutics, Mannheim, Germany, and Gaithersburg, Maryland.

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Coronary Artery DiseasesEffectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial)☆

Abstract

Section snippets

Study design

Results

Discussion

Lancet

Am J Cardiol

Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction

Circulation

Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction

Circulation

Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator failsresults of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial

Circulation

Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty

Circulation

Coronary Artery Diseases
Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial)☆