The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy

doi:10.1016/S0002-9343(96)80075-1

The American Journal of Medicine

Volume 101, Issue 2, August 1996, Pages 184-191

https://doi.org/10.1016/S0002-9343(96)80075-1 Get rights and content

PURPOSE:

The aim of this study was to determine the proportion of patients with acute myocardial infarction (AMI) excluded from thrombolytic therapy on a national basis and to evaluate the prognosis of these patients by reasons of ineligibility and according to the alternative therapies that they received during hospitalization.

PATIENTS AND METHODS:

During a national survey, 1,014 consecutive patients with AMI were hospitalized in all the 25 coronary care units operating in Israel.

RESULTS:

Three hundred and eighty-three patients (38%) were treated with a thrombolytic agent and included in the GUSTO study. Ineligible patients for GUSTO were treated: (1) without any reperfusion therapy (n = 449), (2) by mechanical revascularization (n = 97), or (3) given 1.5 million units of streptokinase (n = 85) outside of the GUSTO protocol. The in-hospital and 1-year post-discharge mortality rates were 6% and 2% in patients included in the GUSTO study; 6% and 5% in those mechanically reperfused; 15% and 10% in those treated with thromoblysis despite ineligibility for the GUSTO trial, and 15% and 13% among patients not treated with any reperfusion therapy.

CONCLUSIONS:

Ineligibility for thrombolysis among patients with AMI remains high. Patients ineligible for thrombolysis according to the GUSTO criteria, but nevertheless treated with a thrombolytic agent were exposed to an increased risk.

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Cited by (13)

Characteristics and outcomes of patients with ST-segment elevation myocardial infarction excluded from the harmonizing outcomes with revascularization and stents in acute myocardial infarction (horizons-ami) trial
2013, American Journal of Cardiology
Citation Excerpt :
Also, the excluded patients had a substantially greater clinical and angiographic risk profile and markedly greater early and late mortality, bleeding, and composite adverse event rates than the trial eligible patients. Major differences in the baseline clinical characteristics and outcomes between the patients with STEMI enrolled in RCTs and real-world observational studies have been noted from numerous studies assessing the safety and effectiveness of both thrombolytic therapy and primary PCI,7–16 questioning the generalizability of the findings from the RCTs. Few studies in the primary PCI era, however, have examined the outcomes of screened patients not meeting trial eligibility versus those enrolled within the framework of a RCT.
Randomized controlled trials assessing new drugs and devices tend to exclude subjects who are at greatest risk. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial incorporated broader inclusion criteria in an attempt to include a more representative spectrum of patients presenting with ST-segment elevation myocardial infarction (STEMI). To identify the differences between this modern trial and the real world, we analyzed the characteristics and outcomes of patients with STEMI who were screened but not enrolled at a high-volume recruiting center. Of 318 consecutive patients with STEMI who were screened, 200 (62.9%) were randomized, and 118 (37.1%) were excluded. The baseline characteristics and 30-day and 1-year clinical outcomes were compared in the 2 groups. The excluded patients had numerous high-risk features compared to those randomized, including being older (67.0 ± 12.8 vs 63.0 ± 11.4 years, p = 0.004), more often had had a previous MI (34.7% vs 8.0%, p <0.001), Killip class III-IV (27.4% vs 4.0%, p <0.001), and lower hemoglobin (13.4 ± 2.3 vs 14.8 ± 1.5 g/dl, p <0.001). The excluded patients had markedly greater 30-day and 1-year rates of all-cause mortality (17.4% vs 2.0%, p <0.001, and 27.6% vs 2.5%, p <0.001, respectively), major adverse cardiovascular events (death, MI, ischemia-driven target vessel revascularization, and stroke), major bleeding, and net adverse clinical events (major adverse cardiovascular events or major bleeding). On multivariate analysis, Killip class III-IV at presentation, age, left ventricular ejection fraction, and final Thrombolysis In Myocardial Infarction flow grade 3 were independent predictors of outcome. In conclusion, despite the broadened entry criteria of the HORIZONS-AMI trial, 37.1% of all patients presenting with STEMI at a center with a high rate of enrollment were judged to be ineligible and were excluded. The excluded patients had a significantly greater risk profile and markedly increased mortality and adverse events compared to the trial-eligible group.
Primary angioplasty in acute myocardial infarction: Hypothetical estimate of superiority over aspirin or untreated controls
2005, American Journal of Medicine
Citation Excerpt :
Patients deemed ineligible for thrombolysis may account for approximately half of a typical population with myocardial infarction.54,64 They are a high-risk group, receive less revascularization and proven therapies than those who do receive thrombolysis, and outcomes have been shown to be consistently poor with short-term mortality rates between 16.8% and 34.8%.45,51–54,64,65 Within the large group of patients deemed ineligible for thrombolysis are those who are eligible by qualifying ECG and time to presentation criteria but who have contraindications to thrombolysis.
Primary percutaneous transluminal coronary angioplasty (PTCA) in the setting of ST-segment-elevation myocardial infarction has been compared with intravenous thrombolysis, but its effects versus no treatment are not known. Knowledge of the effects of PTCA in this setting is useful as a substantial minority of patients do not receive thrombolysis because of contraindications.
A hypothetical primary PTCA versus placebo/control odds ratio was computed using a recently described statistical technique that employed the logarithm of the odds ratios of the pooled results of meta-analyses of PTCA versus thrombolysis and thrombolysis versus placebo or controlled trials.
Using data from 30 trials, the synthesized odds ratio for mortality for primary PTCA versus placebo/untreated controls is 0.56 (95% confidence interval [CI]: 0.46 to 0.68; P <0.00001), consistent with a 44% reduction. Primary PTCA and aspirin reduces mortality by 69% versus no aspirin (OR = 0.31; 95% CI: 0.21 to 0.45; P <0.00001). In a high-risk group of otherwise eligible patients with thrombolysis contraindications, the absolute benefit is estimated as 93 per 1000 treated (95% CI: 53 to 132 per 1000 treated). The risk of stroke is reduced with primary PTCA (OR = 0.46; 95% CI: 0.30 to 0.71; P = 0.0004).
In this setting, primary PTCA would hypothetically reduce the short-term risk of death by 44%. Despite the use of aggressive antithrombotic regimens, the risk of stroke would also be reduced substantially with primary PTCA.
A randomized trial comparing myocardial salvage achieved by coronary stenting versus balloon angioplasty in patients with acute myocardial infarction considered ineligible for reperfusion therapy
2004, Journal of the American College of Cardiology
Citation Excerpt :
The majority of patients with AMI are considered ineligible for thrombolysis and, therefore, are not afforded the opportunity for early reperfusion (17,18). These ineligible patients can have significant consequences (19). Although a variety of reasons for not providing reperfusion including older age and female gender has been identified (18), the lack of ST-segment elevation on the ECG of presentation, contraindications to thrombolytic therapy, and a >12-h delay from onset of symptoms are the principal ineligibility criteria admitted by current guidelines (13).
We assessed myocardial salvage achieved by reperfusion with percutaneous coronary interventions (PCI) and compared stenting with balloon angioplasty (PTCA) in patients with acute myocardial infarction (AMI) ineligible for thrombolysis.
A substantial proportion of patients with AMI are currently considered ineligible for thrombolysis, and reperfusion treatment is frequently not recommended for them. It is not known whether these patients benefit from PCI.
The Stent or PTCA for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Ineligible for Thrombolysis (STOPAMI-3) trial, a randomized, open-label study, included 611 patients with AMI who were ineligible for thrombolysis (lack of ST-segment elevation on the electrocardiogram, late presentation >12 h after symptom onset, and contraindications to thrombolysis). Patients were randomly assigned to receive either coronary artery stenting (n = 305) or PTCA (n = 306). Scintigraphic myocardial salvage index (proportion of the initial myocardial perfusion defect that was salvaged by reperfusion) was the primary end point of the study.
A considerable myocardial salvage was achieved with both stenting and PTCA. In patients assigned to receive stenting, the median size of the salvage index was 0.54 (25th and 75th percentiles, 0.29 and 0.87), as compared with a median of 0.50 (25th and 75th percentiles, 0.26 and 0.82) in the group assigned to receive PTCA (p = 0.20). Mortality at six months was 8.2% in the group of patients assigned to receive stenting and 9.2% in the group of patients assigned to receive PTCA (p = 0.69).
Patients with AMI who are currently considered ineligible for thrombolysis by conventional guidelines may greatly benefit from primary PCI. The benefit seems to be comparable when a strategy of stenting is compared with a strategy of PTCA in these patients.
Outcome of patients with post acute myocardial infarction ischemia hospitalized in intensive cardiac care units with and without on-site catheterization laboratories
2001, International Journal of Cardiology
Background: This study addresses the impact of availability of on-site catheterization laboratories on the 1-year survival of patients with post-acute myocardial infarction ischemia (P-AMI-I), a high-risk subgroup of AMI patients. Methods: A prospective 5 month national survey was conducted in 1996 in all operating intensive care units (ICCUs) in Israel (N=26) and included 2377 patients. Four hundred and three (17%) had P-AMI-I, 317 of them were admitted to 18 ICCUs with on-site catheterization laboratories (CATH+) and 86 patients to 8 ICCUs without such facilities (CATH−). A retrospective analysis was performed comparing the in-hospital course and 7 day, 1 month and 1 year mortality data of CATH+ vs. CATH− patients. Results: Patient characteristics in both groups were similar with regard to age, gender AMI location, risk factors, hemodynamic parameters on admission and rate of thrombolytic therapy. Of patients in CATH+, 79% were catheterized before hospital discharge vs. 42% in CATH− (P<0.0001), 45 vs. 15% had PTCA (P<0.0001) and 19 vs. 9% had CABG (P<0.05). At 30 days, patients in CATH+ still had significantly more revascularization procedures (71 vs. 48%, P<0.001). Patients hospitalized in ICCUs with CATH+ and CATH− facilities had similar cardiac mortality rates at 7 days (2.0 vs. 2.3%), 30 days (5.7 vs. 4.7%) and at 1 year (7.6 vs. 7.0%). Conclusions: Despite a more invasive strategy used during the index hospitalization of patients with P-AMI-I hospitalized in CATH+ ICCUs, their survival was similar to CATH− patients at 7 days, 30 days and at 1 year follow-up.
Long-term (three-year) prognosis of patients treated with reperfusion or conservatively after acute myocardial infarction
1999, Journal of the American College of Cardiology
OBJECTIVES
This survey sought to assess the frequency of the use of thrombolytic therapy, invasive coronary procedures (ICP) (angiography, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting [CABG]), variables associated with their use, and their impact on early (30-day) and long-term (3-year) mortality after acute myocardial infarction (AMI).
BACKGROUND
Few data are available regarding the implementation in daily practice of the results of clinical trials of treatments for AMI and their impact on early and long-term prognosis in unselected patients after AMI.
METHODS
A prospective community-based national survey was conducted during January–February 1994 in all 25 coronary care units operating in Israel.
RESULTS
Among 999 consecutive patients with an AMI (72% men; mean age 63 ± 12 years) acute reperfusion therapy (ART) was used in 455 patients (46%; thrombolysis in 435 patients [44%] and primary angioplasty in 20 [2%]). Its use was independently associated with anterior AMI location and hospitals with on-site angioplasty facilities, whereas advancing age, prior myocardial infarction (MI) and prior angioplasty or CABG were independently associated with its lower use. The three-year mortality of patients treated with ART was lower than in counterpart patients (22.0% vs. 31.4%, p = 0.0008), mainly as the result of 30-day to 3-year outcome (12.4% vs. 21.1%; hazard ratio = 0.73, 95% confidence interval [CI] 0.52 to 1.03). Independent predictors of long-term mortality were: age, heart failure on admission or during the hospitalization, ventricular tachycardia or fibrillation and diabetes. The outcome of patients not treated with ART differed according to the reason for the exclusion, where patients with contraindications experienced the highest three-year (50%) mortality rate. After ART, coronary angiography, angioplasty and CABG were performed in-hospital in 28%, 12% and 5% of patients, respectively. Their use was independently associated with recurrent infarction or ischemia, on-site catheterization or CABG facilities, non–Q-wave AMI and anterior infarct location. In the entire study population, and in patients with a non–Q-wave AMI, performance of ICP was associated with lower 30-day mortality (odds ratio [OR] = 0.53, 95% CI 0.25 to 0.98, and OR = 0.21, 0.03 to 0.84, respectively), but not thereafter.
CONCLUSIONS
This survey demonstrates the extent of implementation in daily practice of ART and ICP and their impact on early and long-term prognosis in an unselected population after AMI.
A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombolytic therapy: Results of the medicine versus angiography in thrombolytic exclusion (MATE) trial
1998, Journal of the American College of Cardiology
Objectives. The purpose of this study was to determine if early triage angiography with revascularization, if indicated, favorably affects clinical outcomes in patients with suspected acute myocardial infarction who are ineligible for thrombolysis.
Background. The majority of patients with acute myocardial infarction and other acute coronary syndromes are considered ineligible for thrombolysis and therefore are not afforded the opportunity for early reperfusion.
Methods. This multicenter, prospective, randomized trial evaluated in a controlled fashion the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n = 201) with <24 h of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy consisting of aspirin, intravenous heparin, nitroglycerin, beta-blockers, and analgesics.
Results. In the triage angiography group, 109 patients underwent early angiography and 64 (58%) received revascularization, whereas in the conservative group, 54 (60%) subsequently underwent nonprotocol angiography in response to recurrent ischemia and 33 (37%) received revascularization (p = 0.004). The mean time to revascularization was 27 ± 32 versus 88 ± 98 h (p = 0.0001) and the primary endpoint of recurrent ischemic events or death occurred in 14 (13%) versus 31 (34%) of the triage angiography and conservative groups, respectively (45% risk reduction, 95% CI 27–59%, p = 0.0002). There were no differences between the groups with respect to initial hospital costs or length of stay. Long-term follow-up at a median of 21 months revealed no significant differences in the endpoints of late revascularization, recurrent myocardial infarction, or all-cause mortality.
Conclusions. Early triage angiography in patients with acute coronary syndromes who are not eligible for thrombolytics reduced the composite of recurrent ischemic events or death and shortened the time to definitive revascularization during the index hospitalization. Despite more frequent early revascularization after triage angiography, we found no long-term benefit in cardiac outcomes compared with conservative medical therapy with revascularization prompted by recurrent ischemia.

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Clinical studyThe outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy

PURPOSE:

PATIENTS AND METHODS:

RESULTS:

CONCLUSIONS:

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study

Lancet

Long-term effects of intravenous anistreplase in acute myocardial infarction: final report of the AIMS study

Lancet

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty

N Engl J Med

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

Circulation

Clinical study
The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy