European Heart Journal Advance Access originally published online on November 2, 2007
European Heart Journal 2007 28(23):2873-2878; doi:10.1093/eurheartj/ehm464
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Effect of an invasive strategy on in-hospital outcome in elderly patients with non-ST-elevation myocardial infarction
Herzzentrum Ludwigshafen, Department of Cardiology, Medizinische Klinik B, Bremserstrasse 79,D-67063 Ludwigshafen, Germany
Received 7 March 2007; revised 30 August 2007; accepted 24 September 2007; online publish-ahead-of-print 2 November 2007.
* Corresponding author. Tel: +49 621 503 4045; fax: +49 621 503 4002. E-mail address: uwe.zeymer{at}t-online.de
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Abstract |
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Aims: We sought to investigate the impact of an invasive treatment in elderly patients presenting with non-ST elevation myocardial infarction (NSTEMI) in clinical practice.
Methods and results: We analysed data of consecutive elderly patients (
75 years) with NSTEMI who were prospectively enrolled in the German Acute Coronary Syndromes registry between July 2000 and November 2002. Overall 1936 patients were divided into two groups: 1005 (51.9%) underwent coronary angiography and/or revascularization, 931 (48.1%) received conservative treatment. In the invasive group, percutaneous coronary intervention was performed in 37.5% within 48 h and in 17.6% after 48 h, whereas 9.8% underwent coronary artery bypass grafting within the hospital stay. In-hospital death (12.5 vs. 6.0%, P < 0.0001) and death/myocardial infarction (17.3 vs. 9.6%, P < 0.0001) occurred significantly less often in patients with invasive strategy. After adjustment of the confounding factors in the propensity score analysis the invasive strategy remained superior for mortality (OR 0.55, 95% CI 0.35–0.86) and death and non-fatal myocardial infarction (OR 0.51, 95% CI 0.35–0.75) and 1 year mortality (OR 0.56, 95% CI 0.38–0.81). Major bleeding complications tended to be more frequent in the invasive group (8.8 vs. 5.8%, P = 0.07).
Conclusion: In clinical practice, in elderly patients with NSTEMI, an invasive strategy is associated with an improved in-hospital and 1 year outcome but a trend towards more bleeding complications.
Key Words: Coronary angiography • Revascularization • Non ST-elevation myocardial infarction • Invasive strategy
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Introduction |
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Recent studies have demonstrated an improved clinical outcome among high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACSs) with an invasive strategy including routine use of coronary angiography and revascularization.1–3 Traditionally elderly persons, particulary those with comorbitidies, have been underrepresented in randomized trials of ACSs relative to their disease prevalence.4 The elderly compromise an increasing proportion of patients with NSTE-ACS. In recently published data from an Italian registry, over 35% of the patients were 75 years or older.5 Furthermore, the elderly represent a very high-risk subgroup, but receive less optimal medical and revascularization therapies than younger patients, emphazising the growing importance of investigating treatment modalities in elderly cardiac patients.6–10 In a randomized controlled trial that compared an early invasive management with a conservative ischaemia-guided approach, a significant reduction of death or non-fatal re-infarction was observed at 6 months among patients older than 75 years of age with NSTE-ACS. However, patients with severe comorbid conditions or other serious systemic illness were excluded.11 So far, little is known about the efficacy of a routine cardiac catheterization and revascularization in elderly patients in clinical practice. We therefore analysed data from the German acute coronary syndromes (ACOS) registry to determine the impact of an invasive strategy on in-hospital and 1 year outcome of elderly (
75 years) patients presenting with NSTEMI. |
Methods |
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The acute coronary syndromes registry
The ACOS Registry is a prospective, multi-centre, observational study on current treatment of ACSs (STEMI, NSTEMI, and unstable angina pectoris). Consecutive patients were recruited within the period from June 2000 to November 2002. The participating hospitals were located throughout Germany and included university hospitals, community hospitals, and tertiary care centres all providing intensive care units and early reperfusion therapy. During the entire study period all patients with ACS were prospectively registered and followed during their clinical course to document patient characteristics, acute therapy, hospital course, and 12 ± 2 month outcome. However, the 1 year follow-up was not conducted by all participating hospitals and therefore the 1 year data of
20% of the patients is not known. In the patients with prospectively planned follow-up, 1 year data were 95% complete.
This present study is an analysis of consecutive elderly patients (75 years) with NSTEMI who were divided into an invasive or a conservative group. Patients were included in the invasive group at the time of the coronary angiography. This is in contrast to major randomized clinical trials where invasive and conservative strategies were compared and patients initially randomized to a conservative group remained in this arm even if cardiac catheterization and/or revascularization were necessary due to ischaemia.
Data collection
Data on patient characteristics on admission were recorded, including age, gender, cardiovascular risk factors, concomitant diseases, prior myocardial infarction (MI), prior stroke, prior cardiovascular interventions, and chronic medical treatment, as well as data on symptoms and pre-hospital delay. Data on electrocardiografic findings, biochemical markers, reperfusion therapy, and adjunctive therapy were documented. At discharge, outcome and major cardiovascular and cerebrovascular adverse events were recorded.
Every participating centre was committed by written consent to include every consecutive patient with ACS. All patients gave informed consent for processing their anonymous data. Data were collected on three record forms by the treating physicians. Completed data sheets were sent to the central data processing centre Institut für Herzinfarktforschung Ludwigshafen for uniform monitoring and registration. Source data verification was performed by comparison of the registry data with hospital records in randomly selected patients in 20 randomly selected participating centres. The study was approved by the Ethics Committee of Landesärztekammer Mainz.
Definitions
NSTEMI was diagnosed in the presence of the two following criteria: persistent angina pectoris for >20 min and an elevation of troponin T or I. Raised levels were considered those exceeding the upper normal level at the local laboratory at each participating site. Re-infarction was defined as recurrent angina and re-elevation of cardiac markers or angiographic re-occlusion. Bleeding complications were classified as major when blood transfusions were required or considered clinical relevant by the treating physician. Stroke was defined as the occurrence of persistent specific neurological deficits. Serum creatinin >2 mg/dL was classified as renal insufficiency.
Statistical methods
Data are presented as absolute numbers, percentage, or medians with 25th and 75th percentiles as appropriate. Whenever possible, percentages were used to describe patient populations. The frequencies of categorial variables in two populations were compared by 
2 test and by calculating odds-ratios (OR) and 95% confidence intervals (CI). Continuous variables were compared by Mann–Whitney–Wilcoxon test. The effect of an invasive treatment on hospital death and the composite of death and MI was evaluated by calculating the OR and the 95% CI. Control of potential confounders was attempted by constructing a propensity score using logistic regression.12 The propensity score was the probability that a patient would receive either invasive or conservative strategy and was computed using a logistic regression model including the following variables: age, sex, prior MI, prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), prior stroke/transient ischaemic attack (TIA), peripheral arterial disease, diabetes, smoking, hypercholesterolaemia, hypertension, obesity (BMI 30 kg/m2), renal insufficiency, heart rate 100/min, systolic blood pressure 
100 mmHg, cardiogenic shock, and significant first-order interaction (alpha = 0.05). The C-statistic for propensity score models were 0.80. The patients were divided into quintiles defined by their probabilities (propensity scores). Balance of the covariables across the two groups was achieved after adjustment for the propensity score. The balance was tested statistically by linear regression for continuous variables and logistic regression for the dichotomous variables.
The propensity score quintiles (coded as a class variable with 4 degrees of freedom) were then added to the final logistic regression model. The balance was tested statistically by linear regression for continuous variables and logistic regression for dichotomous variables (Table 3).
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The following variables were added for the propensity score analysis of the 12 ± 2 month follow-up: no evaluation of left-ventricular function, reduced left-ventricular function (ejection fraction <40%), treatment with aspirin, beta-blocker, ACE-inhibitor, and statin at discharge. Significant interactions of propensity score quintile and covariates were: age x propensity score, and heart rate >100 b.p.m. x propensity score. The C-statistic for propensity score models were 0.84.
P-values <0.05 were considered significant. All P-values are results of two-tailed tests. The analysis was performed with the SAS© system release 8.2 on a personal computer (SAS Institute, Inc., Cary, NC).
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Results |
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Baseline characteristics
From 2000 and 2002, a total of 16 817 consecutive patients from 155 hospitals with ACSs were enrolled into the ACOS registry. For the present analysis, 1936 patients (
75 years) with NSTEMI were included and divided into two groups: 51.9% of the patients underwent coronary angiography and revascularization if indicated (n = 1005), 48.1% received conservative treatment (n = 931). The baseline characteristics of the patients in the two different groups are shown in Table 1.
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Coronary angiography
The distribution of one-, two-, and three-vessel disease in the invasive group was 26, 27, and 47%, respectively.
Revascularization
From the invasive group, 377 patients (37.5%) were treated with PCI within 48 h, another 177 patients (17.6%) during the index hospital stay. Ninety-eight patients (9.8%) underwent CABG during the index hospitalization. Overall 353 patients (35.1%) of the invasive group were not revascularized (Table 2).
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Medical treatment
The elderly who underwent an invasive procedure were more likely to receive guideline-recommended medication. They were more often treated with aspirin, clopidogrel, GP IIb/IIIa inhibitors, beta-blockers, and statins. More conservative patients received low-molecular weight heparin, more invasive patients intravenous heparin. The percentage of patients treated with ACE-inhibitors was similar in both groups (Table 2).
Hospital complications
In-hospital mortality (6.0 vs. 12.5%, P < 0.0001) and the combined endpoint of death and non-fatal re-infarction (9.6 vs. 17.3%, P < 0.0001) were lower in the patients undergoing cardiac catheterization compared with the group with conservative strategy (Figure 1). The C-statistic for propensity score models were 0.80. The patients were divided into quintiles defined by their probabilities (propensity scores). Balance of the covariables across the two groups as shown in Table 3 was achieved after adjustment for the propensity score. The balance was tested statistically by linear regression for continuous variables and logistic regression for the dichotomous variables. After adjustment for baseline variables in the propensity score analysis, the invasive strategy remained superior for mortality and death and non-fatal re-infarction (Table 4). The incidence of non-fatal stroke was lower in the patients assigned to coronary angiography (1.1 vs. 2.8%, P < 0.01) (Figure 1). There was a trend towards a higher rate of major bleeding complications in the invasive group (8.8 vs. 5.8%, P = 0.07) (Figure 1). Among patients with an invasive strategy, the incidence of death was 5.5% in the PCI group, 8.2% in the CABG group, and 6.1% in the conservatively treated group, respectively. The rates of death and non-fatal re-infarction in the three subgroups were 10.0, 13.3, and 7.8% (Figure 2).
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Follow-up
Mortality (10.7 vs. 27.9%, P < 0.0001) was lower in patients with an invasive strategy 12 ± 2 months after discharge. Among invasive patients, the incidence of death was 11.1% in the PCI group, 14.5% in the CABG group, and 15.2% in the conservatively treated group. After adjustment in the propensity score analysis a significant risk reduction in mortality persisted in patients with invasive strategy (Table 4).
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Discussion |
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Our analysis is one of the first evaluations of a large registry with NSTEMI patients, which investigates the impact of an invasive strategy in elderly on in-hospital outcome. In our study, elderly patients with a lower risk profile were more likely to undergo diagnostic coronary angiography and revascularization. First of all, the invasive patients were significantly younger. Secondly, they had a lower incidence of cardiogenic shock on admission, diabetes, renal insufficiency, and prior atherothrombotic events, suggesting that the biological age also had a major impact on the clinicians' decision to conduct a coronary angiography. Furthermore, they received more often a guideline-recommended adjunctive therapy. These findings are in concordance with prior observations of physician management of ACSs. Investigators have universally observed that the use of cardiac catheterization and antithrombotic therapy declines as the patients get older and sicker, even when no contraindications exist.6,8–10 In this context, the uncertainty in the medical care of older patients plays a major role. In randomized controlled clinical trials conducted in patients with ACSs, the elderly have been underrepresented.4 Moreover, due to the higher rate of comorbidity, the elderly patients face a higher risk for complications in invasive procedures relative to younger patients. However, with regard to the less favourable baseline profile, the increased frequency of complications after cardiac catheterization and revascularization is reasonable.13–14
In our evaluation, 56% of the patients with invasive strategy were treated with PCI and 9.8% underwent CABG during hospitalization, whereas 35.1% were not revascularized. This revascularization rate is comparable with that reported in randomized trials conducted in the elderly.11
The incidence of death and the composite of death and non-fatal re-infarction during the index hospitalization were significantly lower in the invasive group. However, the reduction in the rate of non-fatal re-infarction just missed the level of significancy. One possible explanation is that re-infarction might have been fatal in a high proportion of patients and events were reported in a hierachical order, therefore masking a reduction in the overall rate of fatal and non-fatal reinfarction. Among patients with invasive strategy, due to the peri-operative risk and selection bias, the incidence of hospital death and non-fatal reinfarction was highest in the CABG-patients, whereas mortality was lowest in the PCI group and re-infarction rate in the conservatively treated patients. However, at 1 year follow-up the mortality rate among the invasive group was lower in patients with PCI or CABG compared with medically managed patients.
As this evaluation is not a randomized, controlled study and the baseline characteristics between the two groups are very different a propensity score analysis was used to control potential confounders. Several factors that have a major impact on the prognosis were taken into account. After adjustment of the confounding variables as baseline characteristics, medical history, risk factors and findings at admission in the propensity score analysis, the invasive strategy remained superior in terms of hospital mortality and death/MI.
The early benefit of an invasive strategy persisted up to 1 year. A significant risk reduction for 1 year mortality could also be observed. Our results are in line with the findings of a subgroup analysis of the TACTICS-TIMI (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy—Thrombolysis in Myocardial Infarction) 18 trial, where patients hospitalized with unstable angina and NSTEMI were randomly assigned to an early interventional or conservative ischaemia-guided procedure. Among elderly (75 years an older), the invasive management strategy conferred to a significant reduction of non-fatal re-infarction and MACE (Major Adverse Cardiac Events) at 6 months. In patients younger than 75 years, a significant reduction of cardiovascular events could not be observed. The occurrence of death tended to be lower in elderly, but the difference was not significant.11 As ACOS is a clinical registry for ACS and not a randomized clinical trial, high-risk patients with renal insufficiency, cardiogenic shock or resuscitation were also enrolled. The absolute reduction of hospital mortality adds up to over 6% and the relative reduction to over 46%. Due to a higher risk profile, the ‘real-world’ patient seems to gain even more benefit from an invasive management, compared with patients in randomized trials with partly low-risk patients.
In addition, in another analysis of a registry with over 500 elderly with NSTE-ACS, De Servi et al.5 identified a conservative strategy as an independent predictor of ischaemic events at 30 days. The APPROACH (Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease) study captured all patients undergoing cardiac catheterization and revascularization in the province of Alberta (Canada) in the late 90's. Interestingly, elderly patients had greater absolute risk reductions associated with surgical or percutaneous revascularization than younger patients.15 In the TIME (Trial of Invasive vs. Medical therapy in Elderly patients) trial, the risk–benefit ratio of invasive vs. optimized medical treatment in patients aged 75 years or older with stable angina was evaluated. After 1 year, no significant differences in the rate of death or non-fatal MI could be shown. However, among patients assigned to an invasive procedure, a later hospitalization for revascularization was less likely.16
Clinicians' reluctance to use an invasive strategy in elderly with NSTEMI has been potentially justified by the high-risk of complications. In a large observational study of patients with NSTE-ACS, a higher risk for stroke associated with an invasive management was observed.17 In our analysis, we found no such increase among elderly. On the contrary, the incidence of stroke was lower in the patients assigned to coronary angiography. In the subgroup analysis of the TACTICS-TIMI trial, an increased risk of bleeding complications after routine invasive management was seen. Bach et al.11 observed a higher frequency of major bleeding and blood transfusions during the index hospitalization in invasive patients. In our registry, the rate of major bleedings among patients assigned to an invasive strategy tended to be higher. The more aggressive antithrombotic treatment seems to play a decisive role. In this finding, those selected for coronary angiography were more likely to receive aspirin, clopidogrel, and GP IIb/IIIa inhibitors. In an analysis of the impact of age on outcome among patients enrolled in PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable Angina Receptor Suppression Using Integrillin Therapy), a significant increase of moderate and severe bleeding was associated with use of eptifibatide in elderly compared with younger patients with NSTE-ACS, despite a lower rate of invasive procedures.18
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Limitations |
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The present analysis is not a randomized, controlled study evaluating the impact of an invasive strategy in elderly presenting with NSTEMI. In the ACOS registry, the treatment strategy was left to the discretion of the physician. This could result in selection bias, which cannot be fully eliminated by using a propensity score.
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Summary |
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In conclusion, our data shows that elderly with a lower risk profile are more likely to undergo a coronary angiography and revascularization. In clinical practice, an invasive strategy resulted in a significant reduction of hospital mortality and death/MI, but was associated with a trend towards more bleeding complications. These results indicate that an invasive strategy is feasible in a substantial proportion of elderly with NSTEMI and is linked with a better in-hospital outcome.
Conflict of interest: none declared.
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References |
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- Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakies N, Neumann FJ, Robertson DH, DeLucca PT, DiBattiste PM, Gibson CM, Braunwald E, TACTICS-TIMI 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med (2001) 334:1879–1887.
- Frisc II Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: Frisc II prospective randomised multicentre study. Fragmin and fast revascularisation during instability in coronary artery disease investigators. Lancet (1999) 354:708–715.[CrossRef][Web of Science][Medline]
- Spacek R, Widimsky P, Straka Z, Jiresova E, Dvorak J, Polasek R, Karel I, Jirmar R, Lisa L, Budesinsky T, Malek F, Stanka P. Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomised trial. The VINO Study. Eur Heart J (2002) 23:230–238.
[Abstract/Free Full Text] - Lee PY, Alexander KP, Hammill BG, Pasquall SK, Petersen ED. Representation of elderly persons and women in published randomised trials of acute coronary syndromes. JAMA (2001) 286:708–713.
[Abstract/Free Full Text] - De Servi S, Cavallini C, Dellavalle A, Santoro GM, Bonizzoni E, Marzocchi A, Politi A, Pesaresi A, Mariani M, Chierchia S, for the ROSAI-2 Investigators. Non-ST-Elevation acute coronary syndrome in the elderly: treatment strategies and 30-day outcome. Am Heart J (2004) 147:830–836.[CrossRef][Web of Science][Medline]
- Alexander KP, Roe MT, Chen AY, Lytle BL, Pollack CV Jr, Foody JM, Boden WE, Smith SC Jr, Gibler B, Ohman EM, Peterson ED, for the CRUSADE Investigators. Evolution in cardiovascular care for elderly patients with non-ST-segment elevation acute coronary syndromes. JACC (2005) 46:1479–1487.
[Abstract/Free Full Text] - Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA (2000) 284:835–842.
[Abstract/Free Full Text] - Liistro F, Angioli P, Falsino G, Ducci K, Baldassarre S, Burali A, Bolognese. Early invasive strategy in elderly patients with non-ST elevation acute coronary syndrome: comparison with younger patients regarding 30 day and long term outcome. Heart (2005) 91:1284–1288.
[Abstract/Free Full Text] - Rosengren A, Wallentin L, Simoons M, Gitt AK, Behar S, Battler A, Battler A, Hasdai D. Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey. Eur Heart J (2006) 27:789–795.
[Abstract/Free Full Text] - Yan RT, Yan AT, Tan M, Chow CM, Fitchert DH, Ervin FL, Cha JYM, Langer A, Goodman SG, for the Canadian Acute Coronary Syndromes Registry Investigators. Age-related differences in the management and outcome of patients with acute coronary syndromes. Am Heart J. 151:352–359.
- Bach RG, Cannon CP, Weintraub WS, DiBattiste PM, Demopoulos LA, Andersen HV, DeLucca PT, Mahoney EM, Murphy SA, Braunwald E. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med (2004) 141:186–195.
[Abstract/Free Full Text] - D'Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med (1998) 17:2265–2281.[CrossRef][Web of Science][Medline]
- Feliciano J, Fiarresga AJ, Timoteo AT, Pelicano N, Cacela D, Ferreira R, Goncalves JM, Quinha J. Primary coronary angioplasty in the elderly. Rev Port Cardiol (2005) 24:205–214.[Medline]
- Munoz JC, Alonso JJ, Duran JM, Gimeno F, Ramos B, Garcimartin I, de la Fuente L, Gomez I, Fernández-Avilés F. Coronary stent implantation in patients older than 75 years of age: clinical profile and initial and long term (3 years) outcome. Am Heart J (2002) 143:620–626.[CrossRef][Web of Science][Medline]
- Graham MM, Ghali WA, Faris PD, Galbraith PD, Norris CM, Knudtson ML, for the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease Investigators. Survival after coronary revascularization in the elderly. Circulation (2002) 105:2378–2384.
[Abstract/Free Full Text] - Pfisterer M, Buser P, Osswald S, Allemann U, Amann W, Angehrn W, Eeckhout E, Erne P, Estlinbaum W, Kuster G, Moccetti T, Naegeli B, Rickenbacher P, Trial of Invasive versus Medical therapy in Elderly patients Investigators. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs optimized medical treatment strategy: one-year results of the randomized TIME trial. JAMA (2003) 289:1117–1123.
[Abstract/Free Full Text] - Yusuf S, Flather M, Pogue J, Hunt D, Varigos J, Piegas L, Avezum A, Anderson J, Keltai M, Budaj A, Fox K, Ceremuzynski L. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischaemic Syndromes) Registry Investigators. Lancet (1998) 352:507–514.[CrossRef][Web of Science][Medline]
- Hasdai D, Holmes DR Jr, Criger DA, Topol EJ, Califf RM, Harrington RA. Age and outcome after acute coronary syndromes without persistent ST-segment elevation. Am Heart J (2000) 139:858–866.[Web of Science][Medline]
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