Severity of heart failure, treatments, and outcomes after fibrinolysis in patients with ST-elevation myocardial infarction

Amir Kashania, Robert P. Giuglianob,*, Elliott M. Antmanb, David A. Morrowb, C. Michael Gibsonb, Sabina A. Murphyb and Eugene Braunwaldb

a Department of Internal Medicine, Rochester General Hospital, Rochester, NY, USA
b TIMI Study Group, Brigham and Women's Hospital, Cardiovascular Medicine, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA

Received February 5, 2004; revised April 28, 2004; accepted May 5, 2004 * Corresponding author. Tel.: +1-617-278-0145; fax: +1-617-734-7329
rgiugliano{at}partners.org


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Aims To define the clinical characteristics, co-morbidities, treatment, and clinical outcomes of patients with varying degrees of heart failure (HF) complicating ST-elevation myocardial infarction (STEMI), and to identify patients at high risk for HF following fibrinolysis.

Methods and results 15,078 STEMI patients enrolled in a worldwide fibrinolytic trial (InTIME-II) were categorised into one of four hierarchical, mutually exclusive groups of HF: shock (, 5%); severe HF (, 7%); mild HF (, 11%); no HF (, 77%). In a multivariable model, anterior MI (OR 1.8, 95% CI [1.6; 1.9]), age >=65 (OR 1.8 [1.6; 2.0]), prior HF (OR 3.3 [2.6; 4.2]), and creatinine clearance 60 mL/min (OR 1.8 [1.6; 2.1]) were the four most powerful correlates of HF. Although 30-day mortality was sixfold higher for patients with HF (18.9% vs. 3.1%, ), these patients were less likely to undergo angiography (30% vs. 40%, ) and revascularisation (19% vs. 25%, ), than patients without HF. Likewise, angiotensin-inhibitors and ß-blockers were not optimally utilised in patients with HF following MI.

Conclusions During the index admission following fibrinolysis 23% of patients had HF. Despite a higher risk profile, patients with more severe HF were treated less aggressively than patients without HF.

Key Words: Heart failure • Acute myocardial infarction • STEMI • Fibrinolysis • Revascularisation • Cardiogenic shock


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Heart failure (HF) complicating myocardial infarction (MI) is associated with a 3–4-fold increase in hospital mortality,1–5 and may be even higher since many prior studies excluded patients with shock or a prior history of HF. The incidence of cardiogenic shock complicating MI ranges from 7% to 15%, and in this subgroup hospital mortality rates may be as high as 78%.6–9 Early revascularisation in patients with shock significantly reduces short and long-term mortality.10,11 Thus, the identification of patients at increased risk of HF in the immediate post-MI period3,5 could aid in targeting more aggressive treatment, thereby leading to improved outcomes in these patients.

We explored the baseline characteristics, therapies, and clinical outcomes of patients with varying degrees of HF in the Intravenous NPA for the treatment of infarcting myocardium early (InTIME)-II study,12 a large international trial of fibrinolytic therapy in ST-elevation MI (STEMI). We hypothesised that patient characteristics, treatments and outcomes would vary across the spectrum of HF.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The design of the InTIME-II trial12 has been previously described. Briefly, the study included patients 18 years of age and older who presented within 6 h of onset of symptoms and had either ST-elevation in any two contiguous leads or new left bundle branch block. Patients who were in cardiac shock (defined as Killip Class IV) at the time of screening were excluded from the trial, and no data are available on these patients. Other major exclusion criteria included any of the following: increased risk of bleeding, history of cerebrovascular accident, systolic blood pressure (SBP) >=180 mmHg, or diastolic blood pressure >=110 mmHg. A total of 15,078 patients were randomised between 1997 and 1998 in 855 hospitals across 35 countries and six continents.

Patients from the InTIME-II database were categorised into one of four mutually exclusive groups of HF based on data obtained during their index hospitalisation: shock, severe HF, mild HF, and no HF. The definitions are given in Table 1 . Baseline characteristics, in-hospital therapies, and clinical outcomes were compared across the spectrum of HF. Since there was no difference in the distribution of the degree of HF by fibrinolytic therapy, we present data in this manuscript pooled across treatments. Causes of death in the InTIME-II trial were determined by trained clinical investigators using a prospectively designed case record form with 12 pre-specified and defined causes of death.


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Table 1 Cohort definitions

 
The thrombolysis in myocardial infarction (TIMI) risk score for STEMI is a simple bedside tool that provides an integer score that provides risk stratification with respect to mortality in STEMI patients.13,14 Insofar as Killip Class is by definition used to characterise HF, this variable was removed from the conventional STEMI TIMI Risk Score. After removal of the Killip Class as a variable, the association of the STEMI TIMI risk score with 30-day death or cardiogenic shock/severe HF was then evaluated.

Since age and haemodynamic status were important determinants of poor outcome, we also explored these variables obtained at presentation using a simple risk index15 calculated as follows: risk index=(age in decades)2xHR/SBP. We explored the interaction between invasive procedures and three important clinical variables (geographic region, age, and renal function), as prior studies have demonstrated lower rates of procedures outside North America, in the elderly, and among patients with impaired renal function.16–18

Statistical analysis
Data were obtained from case record forms submitted in the trial. Baseline characteristics were compared using test for trend across ordered groups. All statistical tests were two-sided and nominal -values with a threshold of 0.05, without adjustment for multiple comparisons, were used in these exploratory analyses. Multivariable logistic models were constructed using backward selection with significance set at . The -score was used to identify variables with the greatest predictive power. The -statistic was used to quantify the discriminatory capacity of different multivariable models. All baseline variables on univariate analyses with were included as candidate variables in the multivariable models. Weights of variables in the prediction rule were based on the odds ratios (rounded to the nearest whole number) derived from the logistic model.

Kaplan–Meier curves were generated for mortality through 1 year of follow-up. The log rank test was used to test the equality of the survivor function across groups, and the test for trend of the survivor function was performed across the ordered groups.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Of the 15,078 patients enrolled, 3420 patients (23%) developed HF during the index admission following fibrinolytic administration. There were 719 (5%) patients with shock (since cardiogenic shock at presentation was an exclusion criteria, these were patients who developed shock after randomisation), 1082 (7%) with severe HF, 1619 (11%) with mild HF, and 11 658 (77%) remained free of HF. Three quarters of the patients with HF during the index admission developed HF on hospital day 0 or 1, while 72%, 53%, and 92% developed HF within the first 36 h for the shock, severe, and mild HF groups, respectively.

Baseline characteristics, prior medications, and hospital characteristics across the spectrum of HF are detailed in Table 2 . Patients with shock were less likely to receive ß-blockers and angiotensin I converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) but more likely to receive inotropic agents when compared to other classes of HF (Table 3 ). ß-Blockers and ACE-I/ARB were under-utilised even in patients free of HF. A low percentage (2–5%) of patients across all groups received glycoprotein (GP) IIb/IIIa receptor blockers, even when accounting for use only among patients undergoing PCI (14–24%).


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Table 2 Baseline characteristics of heart failure patients

 

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Table 3 In-hospital medications

 
Multivariable correlates of HF are displayed in Fig. 1 . The four variables that contributed most to the model were anterior infarct (odds ratio (OR) 1.8, 95% confidence interval [1.6; 1.9]), age >=65 (OR 1.8 [1.6; 2.0]), prior HF (OR 3.3 [2.6; 4.2]), and creatinine clearance 60 mL/min (OR 1.8 [1.6; 2.1]) (Fig. 1). Excluding patients with a prior history of HF did not substantially change the model.



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Fig. 1 Multivariable correlates of heart failure with . Variables are ranked in order of their contribution to the model as assessed by the z-score. The model was also adjusted for the following variables ( on multivariable analysis): sex; weight; prior diabetes, hypertension, angina, MI, percutaneous coronary intervention, renal insufficiency, coronary artery bypass graft, peripheral vascular disease, and cerebrovascular disease; smoking, prior ß-blocker, calcium-channel blocker, nitrate, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, glycoside, and hypolipidaemic therapy use; geographic region; availability of 24-h percutaneous coronary intervention. AF, atrial fibrillation; CI, confidence interval; CrCl, creatinine clearance (mL/min); HF, heart failure; HR, heart rate; MI, myocardial infarction; OR, odds ratio; SBP, systolic blood pressure. NC Lytic, Non-cardiologist administered fibrinolytics.

 
Patients with HF had higher mortality rates at 30 days (18.9% vs. 3.1%, ) and 1 year (25.2% vs. 5.3%, ) compared to patients without HF during the index admission. One-year Kaplan–Meier survival curves demonstrate an increasing mortality rate among patients with increasingly more severe grades of HF (Fig. 2 ). Patients aged >=65 had higher mortality at 1 year across the four groups of HF compared to those under age 65 (Fig. 3(a) and (b) ). A similar pattern was seen in women compared to men (Fig. 3(c) and (d)).



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Fig. 2 One-year Kaplan–Meier survival curves show decreasing mortality with more severe grades of heart failure.

 


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Fig. 3 One-year Kaplan–Meier survival curves. (a) Patients 65 years of age and older, (b) patients under 65 years old, (c) women, (d) men. Patients aged 65 and older had lower survival at 1 year across the four groups of heart failure compared to those under 65 (hazard ratio 1.32, interaction ). Similarly, women had a lower 1-year survival rate than men (hazard ratio 1.23, interaction ). HF, heart failure.

 
The majority of the deaths occurred within the first 2–3 weeks of enrollment. Among patients with severe HF or shock during the index admission, the predominant cause of death in the first 30 days was HF (53%) (Table 4 ). In patients with either mild or no HF, there were few deaths due to HF (3.3% and 5.3%, respectively), while non-cardiac aetiologies, myocardial rupture, and intra-cranial haemorrhage were relatively more frequent causes of death. Survival curves between 31 and 180 days were relatively flat in each of the four HF groups: 99% for no HF, 96% for mild HF, and 93% for severe HF, and 93% for shock (trend ).


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Table 4 30-day causes of mortality in the various heart failure groups

 
A modified TIMI risk score for STEMI, which excluded Killip Class, showed a strong graded association with the risk of death or shock/severe HF ( for trend 0.001) (Fig. 4 ). At higher risk scores, a greater proportion of events were death rather than non-fatal shock/severe HF, while at lower risk scores the reverse was true. For example, patients with a risk score greater than 6 had a 30.1% mortality rate and a 14.5% rate of non-fatal shock/severe HF (total event rate=44.6%). However, patients with a risk score of zero had only a 0.9% mortality and 3.5% non-fatal shock/severe HF rate (total event rate=4.6%). A simple risk index,15 which utilises three of the most predictive variables (age, heart rate, and systolic blood pressure) was a very strong predictor of the presence and severity of heart failure () (Fig. 5 ).



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Fig. 4 TIMI risk score for STEMI (excluding Killip Class) to predict 30-day death or shock/severe heart failure. HF, heart failure.

 


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Fig. 5 Incidence of death and heart failure among patients stratified by the simple risk index. Quintiles of risk are shown from lowest (left) to highest (right). Within each stacked bar the percentages of patients with death, shock, severe heart failure, mild heart failure, and no heart failure during the index hospitalisation are shown. The outcomes represented are hierarchical and mutually exclusive. Spearman rank correlation co-efficient , .

 
Although 30-day mortality was highest for shock followed by severe, mild, and no HF, use of angiography and revascularisation followed a "U-shaped curve" (Fig. 6 ), with highest utilisation rates in patients without HF. Overall, patients with HF were less likely to have angiography (30% vs. 40%, ) and revascularisation (19% vs. 25%, ) compared to patients without HF. Even after multivariable adjustment, the presence of HF during the index hospitalization was associated with 25% reduction in the odds of undergoing angiography.19 The majority of patients who underwent angiography were revascularised, with patients in shock experiencing a slightly higher rate of revascularisation (71%, 59%, 61%, 62% for the four groups, ) among patients who had angiography.



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Fig. 6 30-day angiography and revascularisation. There was a "U-shaped" relationship between the use of invasive procedures and intensity of heart failure following fibrinolytic therapy. Patients with no heart failure had the highest rates of angiography and revascularisation.

 
A similar U-shaped pattern of utilisation of invasive procedure was also present across the various HF categories and the four major geographic regions (Western Europe, Eastern Europe, North America, and Latin America), although rates of procedures varied markedly across the regions (lowest in Eastern Europe with 9–16% angiography, 3–7% revascularisation, and highest in North America with 50–56% angiography, 34–46% revascularisation). The U-shaped pattern of procedure utilisation also was observed when patients were stratified by age (>=65 vs. 65 years) and baseline renal function (creatinine clearance 90 vs. 60–90 vs. 60 mL/min), with one exception. Few patients (23%) with shock and creatinine clearance 60 mL/min underwent angiography, suggesting an important interaction between these variables (interaction ).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Twenty-three percent of patients in a recent worldwide fibrinolytic trial experienced HF during the index hospitalisation. Patients with progressively more severe degrees of heart failure had increasingly more co-morbidities and higher mortality at one year. Our analyses extend previous studies10,11,20 that reported a high short-term mortality rate in patients with cardiogenic shock, by demonstrating a gradation of mortality through one year corresponding to the degree of severity of in-hospital heart failure. Most of the deaths occurred within the first 2–3 weeks, while survival to 30 days was generally associated with low mortality over the remaining year (<=7%), even if shock had developed during the index admission. Since prior studies excluded patients with hypotension,21,22 prior MI,23,24 prior HF,4,22,23,25 and patients older than 75 years,24 these analyses may have underestimated the incidence and mortality rate of HF post-STEMI. Surprisingly, nearly half of previous reports studying HF after MI did not include data on prior HF.2

Similar to previous studies, we found that the most important correlates of HF were anterior infarction,3,9,21,26 older age,3,5,21,27 prior HF,3 and tachycardia.3,5,21 We also demonstrated that patients with creatinine clearance 60 mL/min, atrial fibrillation, and admission to hospitals in cities, and to hospitals in which non-cardiologists most commonly administer fibrinolytics, were more likely to experience HF.

The risk of developing HF in hospitals with different hospital characteristics is a complex issue. While 95% of the patients in US hospitals in this trial had their care directed by a cardiologist, in other regions the percentage was much lower.16 Eastern European patients, compared to other regions, also had a higher prevalence of advanced Killip Class, lower use of aspirin and lipid-lowering agents prior to index hospitalisation, and lower rates of angiography and revascularisation.16

Despite a higher risk profile (older age, greater haemodynamic perturbation, more anterior and large infarctions), patients with more severe HF were less likely to receive angiography and revascularisation than patients with no HF. While patients with shock after STEMI have only a 17–50% rate of in-hospital survival with fibrinolytic therapy alone,10,20,28,29 survival rates of 62–70% were observed in patients undergoing PCI.10,20,28–31 Our results from InTIME-II suggest that the practice at the time this trial was conducted (1997–1998) did not reflect the subsequently revised STEMI guidelines32,33 and the results of the SHOCK10,11 trial of 1999, both of which strongly support use of angiography and revascularisation in patients with HF and shock.

While the use of proven medical therapies in HF patients has been gradually increasing over the past 30 years,2 our study confirms prior findings1,2,5,27 that these drugs remain under-utilised. Even among patients with mild HF and presumably fewer contraindications to ß-blockers and ACE-I, one-third of patients did not receive these proven therapies. Persistent hypotension should be the primary contraindication to the use of ß-blockers and ACE-I in patients with HF complicating STEMI. Since GPIIb/IIIa inhibitors have been demonstrated to reduce mortality in conjunction with PCI,34 their use (except perhaps very early post fibrinolysis35) in this setting also might improve outcomes. Future efforts to reduce infarct size with medications or devices (e.g., cooling therapy) would be desirable since infarct size is a major predictor of HF post fibrinolysis.

Although the TIMI risk score for STEMI13,14 was initially devised to predict mortality after an STEMI, it also predicts shock or severe HF, as well as the composite of death or shock/severe HF, quite well. Furthermore, a large proportion (53%) of early deaths in patients who experienced either severe HF or shock were due to HF. These observations suggest that severe HF, shock, and death form a closely-knit continuum in patients with STEMI.

Patients at high risk for HF and death following STEMI can be identified using clinical variables that are readily available at the time of initial assessment. In addition, we demonstrated that three key variables (age, systolic blood pressure, heart rate) effectively provide the information needed to rapidly determine which patients are most likely to develop heart failure and die.15 The simple risk index could be used by pre-hospital and emergency personnel to triage those patients at highest risk to tertiary care cardiac units. Meanwhile the more extensive risk score is potentially helpful to the treating healthcare providers to identify patients who are particularly likely to benefit from more intensive early medical and interventional therapy.

Study limitations
Our classification of HF after STEMI was applied retrospectively following initial data collection. The InTIME-II trial only included patients with STEMI treated with fibrinolytic therapy. Patients who presented with cardiogenic shock (but not other degrees of HF), severe hypertension, or with increased bleeding risk were excluded from the trial (i.e., patients had to be eligible for thrombolytic therapy), and since the completion of the InTIME-II trial more hospitals utilise primary angiography – thus limiting the generalisations that can be made from our results to other patient populations. Use of medications (other than the fibrinolytic agent) and interventions were left to the discretion of treating physicians in InTIME-II and these co-therapies have evolved over time in response to new data. However, these data were collected prospectively at experienced clinical trial centres using well-defined variables, which not only allowed for more detailed HF definitions than previously reported studies, but also allowed for analysis of various severities of HF. Medication use post discharge and contraindications to therapies (e.g., hypotension, renal failure) were not collected. Lastly, left ventricular function was not routinely assessed in all patients enrolled in the trial.

Conclusions
In conclusion, 23% of patients in a large STEMI clinical trial had HF following fibrinolysis, of whom 5% developed shock, 7% had severe HF, and 11% had mild HF. Patients with anterior wall MI, age >=65 years, prior HF, creatinine clearance 60 mL/min, tachycardia, or hypotension were more likely to experience HF. Patients with more severe HF were less likely to undergo angiography and revascularisation than those without HF, despite having a less favourable prognosis.

Our data suggest that patients in 1997–1998 with severe HF and shock were not treated aggressively with respect to proven therapies, particularly early revascularisation, in contrast to recommendations from the updated STEMI guidelines32,33 and the SHOCK trial10 that were subsequently published in 1999. Since patients with more severe HF and shock following fibrinolysis can be easily identified, and such patients have poor short-term outcomes, prospective evaluation of aggressive medical and invasive therapy in patients at high risk for severe HF or shock is warranted.


    Acknowledgments
 
The InTIME-II Trial was supported by a research grant from Bristol Myers Squibb and Co., Inc.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Spencer FA, Meyer TE, Gore JM, et al. Heterogeneity in the management and outcomes of patients with acute myocardial infarction complicated by heart failure: the National Registry of Myocardial Infarction. Circulation. 2002;105:2605–2610[Abstract/Free Full Text]
  2. Hellermann JP, Jacobsen SJ, Gersh BJ, et al. Heart failure after myocardial infarction: a review. Am. J. Med. 2002;113:324–330[CrossRef][Medline]
  3. Wu AH, Parsons L, Every NR, et al. Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J. Am. Coll. Cardiol. 2002;40:1389–1394[CrossRef][Medline]
  4. Spencer FA, Meyer TE, Goldberg RJ, et al. Twenty year trends (1975–1995) in the incidence, in-hospital and long-term death rates associated with heart failure complicating acute myocardial infarction: a community-wide perspective. J. Am. Coll. Cardiol. 1999;34:1378–1387[CrossRef][ISI][Medline]
  5. Steg PG, Dabbous OH, Feldman LJ, et al. Determinants and prognostic impact of heart failure complicating acute coronary syndromes: observations from the Global Registry of Acute Coronary Events (GRACE). Circulation. 2004;109:494–499[Abstract/Free Full Text]
  6. Goldberg RJ, Samad NA, Yarzebski J, et al. Temporal trends in cardiogenic shock complicating acute myocardial infarction. N. Engl. J. Med. 1999;340:1162–1168[Abstract/Free Full Text]
  7. Rott D, Behar S, Gottlieb S, et al. Usefulness of the Killip classification for early risk stratification of patients with acute myocardial infarction in the 1990s compared with those treated in the 1980s. Israeli Thrombolytic Survey Group and the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group. Am. J. Cardiol. 1997;80:859–864[CrossRef][ISI][Medline]
  8. Goldberg RJ, Gore JM, Alpert JS, et al. Cardiogenic shock after acute myocardial infarction. Incidence and mortality from a community-wide perspective, 1975 to 1988. N. Engl. J. Med. 1991;325:1117–1122[Abstract]
  9. Hasdai D, Topol EJ, Kilaru R, et al. Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials. Am. Heart J. 2003;145:73–79[CrossRef][Medline]
  10. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. should we emergently revascularize occluded coronaries for cardiogenic shock. N. Engl. J. Med. 1999;341:625–634[Abstract/Free Full Text]
  11. Hochman JS, Sleeper LA, White HD, et al. One-year survival following early revascularization for cardiogenic shock. JAMA. 2001;285:190–192[Abstract/Free Full Text]
  12. Intravenous NPA for the treatment of infarcting myocardium early; InTIME-II, a double-blind comparison of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction. Eur Heart J 2000;21:2005–13
  13. Morrow DA, Antman EM, Charlesworth A, et al. TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: an intravenous nPA for treatment of infarcting myocardium early II trial substudy. Circulation. 2000;102:2031–2037[Abstract/Free Full Text]
  14. Morrow DA, Antman EM, Parsons L, et al. Application of the TIMI risk score for ST-elevation MI in the National Registry of Myocardial Infarction 3. JAMA. 2001;286:1356–1359[Abstract/Free Full Text]
  15. Morrow DA, Antman EM, Giugliano RP, et al. A simple risk index for rapid initial triage of patients with ST-elevation myocardial infarction: an InTIME II substudy. Lancet. 2001;358:1571–1575[CrossRef][ISI][Medline]
  16. Giugliano RP, Llevadot J, Wilcox RG, et al. Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II. Eur. Heart J. 2001;22:1702–1715[Abstract/Free Full Text]
  17. Llevadot J, Giugliano RP, Antman EM, et al. Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction. Eur. Heart J. 2001;22:2104–2115[Abstract/Free Full Text]
  18. Stenestrand U, Wallentin L. Early revascularisation and 1-year survival in 14-day survivors of acute myocardial infarction: a prospective cohort study. Lancet. 2002;359:1805–1811[CrossRef][ISI][Medline]
  19. Kashani A, Murphy SA, Giugliano RP. Angiography and revascularization in patients with heart failure following fibrinolysis [abstract]. Am. J. Cardiol. 2003;92:110L
  20. Dauerman HL, Goldberg RJ, White K, et al. Revascularization, stenting, and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. Am. J. Cardiol. 2002;90:838–842[CrossRef][Medline]
  21. O'Connor CM, Hathaway WR, Bates ER, et al. Clinical characteristics and long-term outcome of patients in whom congestive heart failure develops after thrombolytic therapy for acute myocardial infarction: development of a predictive model. Am. Heart J. 1997;133:663–673[ISI][Medline]
  22. Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. N. Engl. J. Med. 1995;332:80–85[Abstract/Free Full Text]
  23. Ali AS, Rybicki BA, Alam M, et al. Clinical predictors of heart failure in patients with first acute myocardial infarction. Am. Heart J. 1999;138:1133–1139[Medline]
  24. Bueno H, Vidan MT, Almazan A, et al. Influence of sex on the short-term outcome of elderly patients with a first acute myocardial infarction. Circulation. 1995;92:1133–1140[Abstract/Free Full Text]
  25. Guidry UC, Evans JC, Larson MG, et al. Temporal trends in event rates after Q-wave myocardial infarction: the Framingham Heart Study. Circulation. 1999;100:2054–2059[Abstract/Free Full Text]
  26. Stone PH, Raabe DS, Jaffe AS, et al. Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location. J. Am. Coll. Cardiol. 1988;11:453–463[ISI][Medline]
  27. Emanuelsson H, Karlson BW, Herlitz J. Characteristics and prognosis of patients with acute myocardial infarction in relation to occurrence of congestive heart failure. Eur. Heart J. 1994;15:761–768[Abstract]
  28. Stomel RJ, Rasak M, Bates ER. Treatment strategies for acute myocardial infarction complicated by cardiogenic shock in a community hospital. Chest. 1994;105:997–1002[Abstract]
  29. Lee L, Bates ER, Pitt B, et al. Percutaneous transluminal coronary angioplasty improves survival in acute myocardial infarction complicated by cardiogenic shock. Circulation. 1988;78:1345–1351[Abstract]
  30. Hochman JS, Boland J, Sleeper LA, et al. Current spectrum of cardiogenic shock and effect of early revascularization on mortality. Results of an International Registry. SHOCK Registry Investigators. Circulation. 1995;91:873–881[Abstract/Free Full Text]
  31. Berger PB, Holmes DR Jr., Stebbins AL, et al. Impact of an aggressive invasive catheterization and revascularization strategy on mortality in patients with cardiogenic shock in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. An observational study. Circulation. 1997;96:122–127[Abstract/Free Full Text]
  32. Van de Werf F, Ardissino D, Betriu A, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur. Heart J. 2003;24:28–66[Free Full Text]
  33. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J. Am. Coll. Cardiol. 1996;28:1328–1428[CrossRef][ISI][Medline]
  34. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13–20[CrossRef][ISI][Medline]
  35. Giugliano RP, Roe MT, Antman EM et al. Percutaneous coronary intervention with concomitant glycoprotein IIb/IIIa blockade following administration of full-dose fibrinolytic therapy (Abstr). Circulation 2001;104:II-87