Killip classification in patients with a”>American Journal of Emergency Medicine (2012) 30, 97-103

Original Contribution

Killip classification in patients with acute coronary syndrome: insight from a multicenter registry^?

Ayman El-Menyar MBChB, MSc^a, Mohammad Zubaid MBChB^b,

Wael AlMahmeed MD^c, Kadhim Sulaiman MD^d, AbdulRahman AlNabti MD^a,

Rajvir Singh PhD^e, Jassim Al Suwaidi MBChB^a,?

^aDepartment of Cardiology and Cardiovascular Surgery, Hamad General Hospital, Doha, Qatar and Weill Cornell Medical School, Doha, Qatar

^bDepartment of Medicine, Faculty of Medicine, Kuwait University, Kuwait

^cSheikh Khalifa Medical City, United Arab Emirates ^dDepartment of Cardiology, Royal Hospital, Muscat, Oman ^eMedical Research Centre, Hamad Medical Corporation, Qatar

Received 29 June 2010; revised 9 October 2010; accepted 10 October 2010

Abstract The purpose of this study was to assess the prognostic value of the Killip classification at the presentation in patients with acute coronary syndrome (ACS). In 2007 and over 5 months, 6704 consecutive patients with ACS were enrolled in the Gulf Registry of Acute coronary events. Patients were categorized according to Killip classification at presentation (Classes I, II, III, and IV). Patients’ characteristics and in-hospital outcomes were analyzed. High Killip classes were defined in 22% of patients. In comparison to Killip Class I, patients with higher Killip class had greater prevalence of Cardiovascular risk factors, presented late, were less likely to have angina, and were less likely to receive antiplatelet, statins, and ?-blockers. Classes II, III, and IV were associated with higher adjusted odds of death in ST- elevation myocardial infarction (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.25-3.69; OR 6.1, 95% CI 3.41-10.86; and OR 28, 95% CI 15.24-54.70, respectively) and non-ST-elevation acute

coronary syndrome (adjusted OR 2.4, 95% CI 1.24-4.82; OR 3.2,95% 1.49-7.02; and OR 9.8, 95% CI 3.79-25.57, respectively). In conclusion, across ACS, patients with higher Killip class had worse clinical profile and were less likely to be treated with evidence-based therapy. High Killip class was independent predictors of mortality in ST-elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Physician in the emergency department should be aware of the importance of clinical examination in the risk stratification in patients presenting with ACS.

(C) 2012

^? Funding: Gulf Registry of acute coronary events (Gulf RACE) is a Gulf Heart Association project and was financially supported by Sanofi Aventis, Paris, and Qatar Telecommunications Company, Doha, Qatar. The sponsors had no role in study design, data collection, data analysis, writing of the report or submission of the manuscript.

* Corresponding author. Tel.: +974 4392464; fax: +974 4392454.

E-mail address: [email protected] (J.A. Suwaidi).

Introduction

Killip classification is a simple clinical tool that has been previously studied in patients with ST-elevation myocardial infarction [1-3]. According to Killip and Kimball criteria, patients were classified into 4 classes during physical examination. Patients in Class I demonstrated no

0735-6757/$ - see front matter (C) 2012 doi:10.1016/j.ajem.2010.10.011

evidence of heart failure . Patients in Class II had findings consistent with mild to moderate HF; patients in Class III demonstrated overt pulmonary edema and patients in Class IV were in cardiogenic shock [2]. Post-MI risk stratification that has been derived from several clinical trials is important to set the appropriate treatment and prognosis. Patients with higher Killip class were found to have more severe angiographic coronary artery disease, higher inci- dence of ventricular dysfunction, and larger myocardial infarctions [2,3]. However, similar data from patients with non-ST-elevation acute coronary syndrome (NSTEACS) are limited. Awareness of patients’ Killip class at the pre- sentation is a crucial step in the risk stratification strategy. Herein, we assess the incidence and prognostic value of Killip classification at the presentation in different types of the ACS spectrum.

Methods

Data are derived from a prospective, observational, multinational, multicenter study of the Gulf Registry of Acute Coronary Events (Gulf RACE). In 2007 and for

Table 1 Clinical and biochemical characteristics in STEMI patients according to Killip class on admission

5 months, Gulf RACE recruited 6704 consecutive ACS patients from 64 hospitals in 6 Middle Eastern countries (Bahrain, Kuwait, Qatar, Oman, United Arab Emirates, and Yemen). The study received ethical approval from the institutional ethical bodies in all participating countries. The rationale and details of Gulf RACE have been described previously [4-6]. Diagnosis of the different types of ACS and definitions of data variables were based on the American College of Cardiology clinical data standards, published in December 2001 [4]. For the purpose of this analysis, ST-elevation myocardial infarction and Left bundle branch block myocardial infarction are grouped together and called STEMI; non-ST-elevation myocardial infarction and unstable angina are grouped together and called NSTEACS. On admission, Killip classification was deter- mined by the attending physician in the accident and emergency department. Specifically, Killip Class I patients had no evidence of heart failure; Killip Class II patients had Mild heart failure with rales involving one third or less of the posterior lung fields and systolic blood pressure of

90 mm Hg or higher; Killip Class III patients had pulmonary edema with rales involving more than one third of the posterior lung fields and systolic blood pressure

Class I		Class II	Class III	Class IV	P
Patients, n (%)	2068 (79)	322 (12.4)	139 (5.3)	86 (3.3)
Age (y), mean +- SD	53 +- 12	59 +- 13?	61 +- 12?	61 +- 12?	b.001
Women, n (%)	255 (12)	51 (16)	36 (26)	24 (28)	.001
Family history of coronary artery disease, n (%)	249 (12)	49 (15)	26 (19)	17 (20)	.01
History of coronary artery disease, n (%)	477 (23)	113 (35)	55 (40)	33 (38)	.001
Previous revascularization, n (%)	101 (5)	40 (12)	22 (16)	10 (12)	.001
Diabetes mellitus, n (%)	623 (31)	122 (38)	63 (45)	31 (36)	.001
Hypertension, n (%)	624 (30)	149 (46)	77 (55)	38 (44)	.001
Smoking, n (%)	1128 (55)	144 (45)	62 (45)	37 (43)	.001
Dyslipidemia, n (%)	319 (15)	67 (21)	54 (39)	27 (31)	.001
Renal failure, n (%)	274 (14)	87 (27)	57 (42)	42 (53)	.001
Body mass index (kg/m2), mean +- SD	28 +- 5	29 +- 6?	28 +- 5 +	27 +- 6 +	b.001
Heart rate (beats per minute), mean +- SD	82 +- 19	93 +- 25?	107 +- 28?	90 +- 44?	b.001
Systolic blood pressure (mm Hg), mean +- SD	136 +- 27	140 +- 31?	141 +- 43?	77 +- 23?	b.001
Diastolic blood pressure (mm Hg), mean +- SD	84 +- 17	87 +- 20 ??	87 +- 24?	46 +- 14?	.001
Serum creatinine (mmol/L), mean +- SD	100 +- 75	118 +- 87?	146 +- 113?	156 +- 155?	b.001
Hemoglobin (g/dL), mean +- SD	14 +- 3	13 +- 2?	15 +- 10?	14 +- +	.02
First Blood sugar (mmol/L), mean +- SD	11 +- 9	12 +- 6 +	16 +- 11?	13 +- 7 ??	.001
Total cholesterol (mmol/L), mean +- SD	5.1 +- 1.4	5.2 +- 1.4 +	5.7 +- 1.5 +	4.7 +- 1.6 +	.001
Serum triglyceride (mmol/L), mean +- SD	1.9 +- 1.5	1.9 +- 1.3 +	2.0 +- 1.3 +	1.6 +- 0.9 +	.43
Ejection fraction b40%, n (%)	249 (17)	91 (38)	64 (62)	28 (67)	.001
Chest pain at presentation, n (%)	1907 (92)	261 (81)	73 (53)	55 (64)	.001
Late presentation, n (%)	552 (27)	141 (45)	61 (47)	30 (39)	.001
GRACE Risk scoring, n (%)					b.001
Low-risk scoring	923 (53)	29 (12)	1 (1.1)	0 (0)
High-risk scoring	271 (16)	143 (58)	82 (90)	58 (97)
Post hoc analysis after Bonferroni correction factor for Killip Class I versus II, I versus III, and I versus IV.
???P b .01.
* P b .001.
?? P b .05.
+ P not significant.

of 90 mm Hg or higher; and Killip Class IV patients had cardiogenic shock with any rales and systolic blood pressure lower than 90 mm Hg [3].

Our findings were compared with the Western studies in 2 subanalyses; patients with signs of heart failure without evidence of cardiogenic shock were grouped as Class II/III in one subanalysis (Fig. 3A) and patients with pulmonary edema and +/- shock were grouped as Class III/IV in another subanalysis (Fig. 3B). Data were analyzed retrospectively from the Gulf RACE registry using case report forms including medical history, physical examination, laboratory findings (electrocardiogram, x ray, echocardiogram, and blood tests), and in-hospital medications, intervention, and outcomes. The primary endpoint of this study was the in- hospital major adverse clinical outcomes (mortality and recurrent ischemia). The GRACE risk model for hospital mortality was used to stratify the risk status of patients at presentation in NSTEACS and STEMI as low (1-180 and 49-125, respectively), intermediate (109-140 and 126-154, respectively), or high scoring (141-372 and 155-319, respectively) [4].

Table 2 Clinical and biochemical characteristics in NSTEACS patients according to Killip class on admission

Data were presented as proportions, medians, or mean +- SD (or SE) as appropriate. Differences in categorical vari- ables between respective comparison groups were analyzed using the ?2 test. One-way ANOVA was used for the asso- ciation between Killip classes (I, II, III, and IV) and con- tinuous clinical variables (i.e., age, heart rate, blood pressure, body mass index, and biochemical variables). Post hoc ana- lysis using Bonferroni correction factor was used to set the comparison between Class I and the other classes individu- ally. The association between different Killip classes and adverse hospital outcomes were examined using univariate and multivariate logistic regression models in ACS patients. Crude and multivariate adjusted odds ratio ORs, with accompanying 95% confidence intervals (CIs), were reported for the respective categories, in comparison with the referent group of patients with Killip Class I in patients with STEMI and NSTEACS. Variables were adjusted for measured cova- riates as age, sex, diabetes mellitus, hypertension, renal failure, smoking, and therapy. P b .05 were considered significant. All data analyses were carried out using the Statistical Package for Social Sciences version 14 (SPSS, Chicago, Ill).

Class I		Class II	Class III	Class IV	P
Patients number, n (%)	3151 (77.2)	552 (13.5)	321 (8)	51 (1.3)
Age (years), mean +- SD	56 +- 12	64 +- 12?	65 +- 11?	67 +- 15?	b.001
Women, n (%)	895 (28)	213 (38)	136 (43)	18 (35)	.001
Family history of coronary artery disease, n (%)	426 (14)	78 (14)	47 (14)	9 (18)	.78
History of coronary artery disease, n (%)	1742 (55)	375 (68)	232 (72)	35 (69)	.001
coronary revascularization, n (%)	647 (21)	144 (26)	69 (22)	12 (24)	.03
Diabetes mellitus, n (%)	1336 (42)	326 (59)	208 (65)	28 (55)	.001
Hypertension, n (%)	1794 (57)	387 (70)	250 (78)	35 (69)	.001
Smoking, n (%)	971 (31)	124 (23)	63 (20)	14 (28)	.001
Dyslipidemia, n (%)	1223 (39)	253 (46)	173 (54)	26 (51)	.001
Renal failure, n (%)	387 (13)	174 (33)	124 (40)	23 (46)	.001
Body mass index (kg/m2), mean +- SD	28 +- 5	29 +- 6?	28 +- 5 +	27 +- 6 +	.11
Heart rate (beats per minute), mean +- SD	83 +- 21	95 +- 23?	107 +- 23?	110 +- 44?	b.001
Systolic blood pressure (mm Hg), mean +- SD	141 +- 23	147 +- 33?	160 +- 38?	120 +- 30?	b.001
Diastolic blood pressure (mm Hg), mean +- SD	83 +- 16	85 +- 18??	91 +- 22?	73 +- 31?	.001
Serum creatinine (mmol/L), mean +- SD	102 +- 88	129 +- 116?	141 +- 131?	176 +- 188?	b.001
Hemoglobin (g/dL), mean +- SD	14 +- 4	13 +- 5?	12 +- 2?	14 +- 9 +	b.001
First blood sugar (mmol/L), mean +- SD	10 +- 12	11 +- 6 +	14 +- 14?	13 +- 7??	.001
Total cholesterol (mmol/L), mean +- SD	5 +- 2.3	5 +- 2.2 +	5.1 +- 1.3 +	5 +- 2 +	.81
Serum triglyceride (mmol/L), mean +- SD	1.9 +- 2	2.0 +- 6 +	1.7 +- 2 +	1.5 +- 0.8 +	.41
High-density lipoprotein (mmol/L), mean +- SD	1.04 +- 1.3	1.03 +- 0.5 +	1.1 +- 0.8 +	0.9 +- 0.3 +	.54
Low-density lipoprotein (mmol/L), mean +- SD	3.3 +- 5	3.2 +- 1.2 +	3.3 +- 1.2 +	3.2 +- 1.7 +	.98
Ejection fraction b40%, n (%)	213 (13)	159 (44)	96 (47)	27 (68)	.001
Chest pain at presentation, n (%)	2687 (85)	271 (49)	72 (22)	12 (24)	.001
Late presentation, n (%)	21 (34)	5 (62)	3 (50)	1 (100)	.001
GRACE risk scoring, n (%)					b.001
Low-risk scoring	1078 (50)	29 (8)	1 (0.5)	0 (0)
High risk scoring	446 (21)	266 (71)	184 (93)	30 (97)
Post hoc analysis after Bonferroni correction factor for Killip Class I versus II, I versus III, and I versus IV.
???P b .01.
* P b .001.
?? P b .05.
+ P not significant.

Class I		Class II	Class III	Class IV	P
In-hospital therapy
Aspirin, n (%)	2039 (99)	315 (98)	135 (97)	78 (91)	.001
Clopidogrel, n (%)	1222 (59)	215 (67)	89 (64)	41 (48)	.001
Heparin, n (%)	1901 (92)	301 (94)	129 (93)	71 (83)	.001
angiotensin-converting enzyme inhibitors, n (%)	1441 (70)	242 (75)	95 (68)	12 (14)	.001
Statins, n (%)	1716 (83)	256 (80)	95 (68)	39 (47)	.001
?-Blockers, n (%)	1426 (69)	155 (48)	30 (22)	7 (8)	.001
Thrombolysis, n (%)	1261 (63)	139 (45)	54 (42)	28 (35)	.001
coronary angiogram, n (%)	341 (17)	70 (22)	31 (22)	6 (7)	.003
In-hospital outcomes
Recurrent ischemia, n (%)	166 (8)	43 (13)	17 (12)	15 (17)	.001
Hospital stay (d), mean +- SD	6.0 +- 4	6.7 +- 4?	7.0 +- 6?	5.3 +- 8 +	.001
Mortality, n (%)	52 (2.5)	26 (8)	37 (27)	57 (66)	.001
Post hoc analysis after Bonferroni correction factor for Killip Class I versus II, I versus III, and I versus IV. * P b .001. + P not significant.

Results

Table 3 In-hospital therapy and outcomes in STEMI patients according to Killip class on admission

Killip classes (I, II, III, and IV) were successfully defined in 6689 patients. Patients with high Killip class (II = 13%, III = 7%, and IV = 2%) were older and had a greater prevalence of previous coronary artery disease, diabetes, hypertension, dyslipidemia, and Renal impairment in com- parison to Killip Class I. Tables 1 and 2 summaries baseline characteristics of patients presenting with ACS in different Killip classes. Patients with STEMI and NSTEACS had

almost similar baseline characteristics, clinical presentation, and risk factors. On admission, patients with higher Killip class sought medical care later than 12 hours and had higher resting heart rate, random blood sugar, and were less likely to have chest pain at presentation. Class II and III patients ranked high in GRACE risk scoring. Fig. 1 demonstrates the distribution of Killip classes across the sex and age groups. Tables 3 and 4 shows the mode of therapy on admission in STEMI and NSTEACS, respectively. Compared with Killip Class I, patients with ACS who had higher Killip class were

Fig. 1 Incidence of Killip class according to (A) sex and (B) age.

Class I		Class II	Class III	Class IV	P
In-hospital therapy
Aspirin, n (%)	3095 (98)	531 (96)	308 (96)	47 (92)	.001
Clopidogrel, n (%)	1660 (53)	226 (41)	123 (38)	23 (45)	.001
Heparin, n (%)	2996 (95)	493 (89)	267 (83)	48 (94)	.001
Glycoprotein inhibitors, n (%)	402 (13)	49 (9)	33 (10)	8 (16)	.03
Angiotensin-converting enzyme inhibitors, n (%)	2087 (66)	450 (82)	260 (81)	21 (41)	.001
Statins, n (%)	2577 (82)	435 (79)	251 (78)	38 (75)	.11
?-Blockers, n (%)	2447 (78)	212 (38)	64 (20)	7 (14)	.001
Coronary angiogram, n (%)	677 (22)	73 (13)	40 (13)	6 (12)	.003
In-hospital outcomes
Recurrent ischemia, n (%)	269 (9)	56 (10)	29 (9)	7 (14)	.38
Hospital stay (d), mean +- SD	4.9 +- 4	6.1 +- 6?	6.8 +- 8?	7.5 +- 6 +	.001
Mortality, n (%)	29 (1)	20 (3.6)	17 (5.3)	9 (17.6)	.001
Post hoc analysis after Bonferroni correction factor for Killip Class I versus II, I versus III, and I versus IV. * P b .001. + P not significant.

less likely to be treated with Antiplatelet therapy, statins, heparin, and ?-blockers. Those patients were less likely to undergo coronary angiography.

Table 4 In-hospital therapy and outcomes in NSTEACS patients according to Killip class on admission

In-hospital outcomes in STEMI and NSTEACS

Compared with Killip Class I, Class II, III, and IV patients had significantly greater worse outcomes. Mortality rates were higher in patients presenting with STEMI when compared with NSTEACS (2.5% vs 1%, 8% vs 4%, 27% vs 5%, and 66% vs 18%, respectively). The incidence of recurrent ischemia was higher in high Killip classes in STEMI patients; however, there were no significant differences in NSTEACS. Prolonged hospital stay was significantly higher within the high Killip classes in both STEMI and NSTEACS (Tables 3 and 4, respectively). However, the low hospital stay in Class IV STEMI patient

Fig. 2 Predictors of in-hospital mortality in patients presenting with ACS.

was related to the great mortality rate in this group of patients. Multivariate models adjusted for age, sex, risk factors, and treatment differences showed that Classes II, III, and IV were associated with increased mortality in ACS (OR 2.4, 95% CI 1.59-3.59; OR 5.5, 95% CI 3.63-8.40;

and OR 27, 95% CI 17.18-43.30, respectively) (Fig. 2). Classes II, III, and IV were associated with higher adjusted odds of death in STEMI (OR 2.1, 95% CI 1.25-3.69; OR 6.1, 95% CI 3.41-10.86; and OR 28, 95% CI 15.24-54.70,

respectively) and NSTEACS (adjusted OR 2.4, 95% CI

1.24-4.82; OR 3.2, 95% 1.49-7.02; and OR 9.8, 95% CI

3.79-25.57, respectively).

Discussion

The current study evaluated the incidence and prognosis of the on-admission Killip classification in patients present- ing with ACS. The key findings of this study were the following: (1) Killip Class II, III, and IV patients had higher risk profiles and rates of major adverse clinical events across ACS. (2) Despite their higher inherent risk, patients with higher Killip class continued to receive less coronary angiography and less evidence-based therapies compared with their counterparts in Class I. This trend of treatment might be related to physician’ selection bias that needs revision. (3) Classes II, III, and IV were associated with higher adjusted odds of death in patients presenting with STEMI as well as NSTEACS. Our findings were consistent with previous data from Western countries that showed that higher Killip class is significant predictor of short-term mortality in the ACS spectrum [3,7-12]. However, in regard to NSTEACS, this is the first report focused on the in- hospital mortality in the 4 Killip classes. The clinical presentation in NSTEACS patients with higher Killip class were reported to be parallel to those found in patients

Fig. 3 Comparison of our findings with that from Western studies. A, in-hospital mortality rate in patients with NSTEACS stratified by Killip Classes I and II/III and whether patients received early ?-blockers. Data from Khot et al [3], Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators [7], the PURSUIT Trial Investigators [8], the PARAGON Investigators [9], the PARAGON B Investigators [10], and Emery et al [11]. B, ?In-hospital and ??30-day mortality rate in varying Killip classes in patients presenting with

NSTEACS from different studies. Data from the current study and from Emery et al [11]. Killip Class I versus II and Class I versus III/IV are statistically significant at P b .001 except Class I versus III/IV in PARAGON A (P = .03).

presenting with STEMI [3]. Furthermore, the risk associated with high Killip class was independent of the ventricular function [3,13-15].

There is no enough data addressing the impact of the mode of revascularization on the mortality in patients with Killip classes. However, the current study showed that the mortality rate was reduced by 2-fold after thrombolysis in Killip Classes I, II, and III. DeGeare et al [2] reported on the predictive value of the Killip classification in patients undergoing primary percutaneous coronary intervention for AMI, the investigators stated that high Killip class was associated with greater in-hospital mortality (2.4%, 7%, and 19% for Classes I, II, and III, respectively) after percutaneous coronary intervention.

The impact of early use of evidence-based medications on patients presenting with Killip classes has not been well studied. In contrast to our study, most of the trials that used ?-blockers early after myocardial infarction excluded patients with higher Killip class. In a meta-analysis of 18 randomized controlled studies [16], the investigators reported that the benefit of early ?-blocker use was exclusively in Class I. Moreover, Emery et al [11] reported

that the apparent benefit of early ?-blockers on mortality was significantly shown in Killip Classes II/III in NSTEACS patients (Fig. 3). The mortality rate in the current study was also comparable with that from other Western studies that were conducted in patients presenting with NSTEACS (Fig. 3) [7-11]. The mortality rate varied from 10% to 20% in class (III/IV) in comparison to 8% in the current study. Moreover, mortality rate varied from 5% to 12% in Class II in comparison to 4% in the current study.

There were a few limitations of the current study. First, data were collected from an observational study. There have been no previous studies on the interrater and intrarater reliability of physicians’ determinations of Killip classifi- cation. Therefore, inaccurate assignment of patients because of these factors is another limitation. The comparative value of Killip classification versus other risk stratification tests, such as nuclear and echocardiographic testing or serum brain natriuretic peptide, is not known [3]. Failure to demonstrate the progression between Killip classes during the hospital course is a limitation of the present study. Further follow-up is needed, as this will fortify our in- hospital findings.

In conclusion, Killip classification is a simple clinical tool in the cardiovascular assessment and risk stratification. Patients with higher Killip class had worse clinical profiles and were less likely to be treated with evidence-based therapy. High Killip classes were independent predictors of mortality in STEMI as well as NSTEACS. Physicians in the emergency department should be aware of the importance of clinical examination in the risk stratification in patients presenting with ACS.

References

1. Neskovic AN, Otasevic P, Bojic M, Popovic AD. Association of Killip class on admission and left ventricular dilatation after myocardial infarction: a closer look into an old clinical classification. Am Heart J 1999;137:361-7.
2. DeGeare VS, Boura JA, Grines LL, et al. Predictive value of the Killip classification in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2001;87: 1035-8.
3. Khot UN, Jia G, Moliterno DJ, et al. Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification. JAMA 2003;290:2174-81.
4. Zubaid M, Rashed WA, Almahmeed W, et al. Management and outcomes of Middle Eastern patients admitted with acute coronary syndromes in the Gulf Registry of Acute Coronary Events (Gulf RACE). Acta Cardiol 2009;64:439-46.
5. El-Menyar A, Zubaid M, Rashed W, et al. Comparison of men and women with acute coronary syndrome in six Middle Eastern countries. Am J Cardiol 2009;104:1018-22.
6. Alsheikh-Ali AA, Al-Mallah MH, Al-Mahmeed W, et al. Gulf RACE investigators. Heart failure in patients hospitalized with acute coronary syndromes: observations from the Gulf Registry of Acute Coronary Events (Gulf RACE). Eur J Heart Fail 2009;11:1135-42.
7. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med 1996;335:775-82.
8. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes: platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy. N Engl J Med 1998;339:436-43.
9. The PARAGON Investigators. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina: platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organization network. Circulation 1998;97:2386-95.
10. The PARAGON B Investigators. Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes. Circulation 2002;105:316-21.
11. Emery M, Lopez-Sendon J, Steg PG, et al. Patterns of use and potential impact of early beta-blocker therapy in non-ST-elevation myocardial infarction with and without heart failure: the Global Registry of Acute Coronary Events. Am Heart J 2006;152:1015-21.
12. Lopez de Sa E, Lopez-Sendon J, Anguera I, et al. Prognostic value of clinical variables at presentation in patients with Non-ST-segment elevation acute coronary syndromes: results of the Proyecto de Estudio del Pronostico de la Angina (PEPA). Medicine (Baltimore) 2002;81: 434-42.
13. Nicod P, Gilpin E, Dittrich H, et al. Influence on prognosis and morbidity of left ventricular ejection fraction with and without signs of left ventricular failure after acute myocardial infarction. Am J Cardiol 1988;61:1165-71.
14. Lee KL, Woodlief LH, Topol EJ, et al, for the GUSTO-I Investigators. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. Circulation 1995;91:1659-68.
15. Launbjerg J, Berning J, Fruergaard P, et al. Risk stratification after acute myocardial infarction by means of echocardiographic wall motion scoring and Killip classification. Cardiology 1992;80:375-81.
16. Al-Reesi A, Al-Zadjali N, Perry J, et al. Do ?-blockers reduce short- term mortality following acute myocardial infarction? a systematic review and meta-analysis. CJEM 2008;10:215-23.