You are here

Article Text

Article menu
Education in Heart
Acute coronary syndromes
Use of risk scores in acute coronary syndromes
  1. Héctor Bueno,
  2. Francisco Fernández-Avilés
  1. Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  1. Correspondence to Dr Héctor Bueno, Department of Cardiology, Hospital General Universitario Gregorio Marañón, Dr Esquerdo, 46, Madrid 28007, Spain; hecbueno{at}jet.es

https://doi.org/10.1136/heartjnl-2011-300129

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Risk is defined as the probability and severity of loss from exposure to a hazard, and can be assessed in different ways. The application of quantitative or qualitative measures to determine the level of risk associated with a specific hazard defines the process of risk assessment. Qualitative risk assessments (ie, high, intermediate or low risk) are based on the presence or absence of certain characteristics (risk markers or factors). These are easy to use but not accurate as there may be wide variations in individual risk within risk subgroups. Quantitative risk assessments, based on algorithms or mathematical formulae, are more precise but more complicated to use. Risk scores are formula generated numbers used for quantitative risk assessment that rank-order individuals according to the likelihood of developing a specific outcome (or combination of outcomes) during a defined time interval.

    Acute coronary syndromes (ACS) are clinical entities characterised by acute symptomatic myocardial ischaemia that has not been triggered by stimuli causing a significant increase of the demand for oxygen by the heart. ACS are usually caused by acute thrombosis of a coronary artery, most frequently associated with lesions caused by chronic coronary atherosclerosis. According to the initial ECG, ACS are classified as presenting with ST segment elevation or non-ST segment elevation. This article will focus on non-ST segment elevation ACS.

    The clinical consequences of ACS range from none or minimal sequelae to early death. Patients with ACS have a relatively high incidence of cardiac events in the short term, particularly myocardial ischaemic recurrences—recurrent angina or myocardial infarction (MI)—but also heart failure, arrhythmias and other events, which may also lead to future further complications. For this reason, ACS require an early pharmacological treatment—based on antithrombotic therapies, anti-ischaemic drugs, and a number of preventive therapies—and, frequently, the revascularisation of one or more diseased coronary arteries, either percutaneously or surgically. There are many therapeutic options that can be used to treat patients with ACS, including pharmacologic treatments—particularly several antithrombotic therapies, such as antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor) and anticoagulant agents (unfractionated heparin, low molecular weight heparins, fondaparinux, bivalirudin)—and strategies for invasive assessment and treatment of coronary lesions (emergent, urgent, or elective coronary angiography and revascularisation). The different combinations of pharmacologic treatments and invasive strategies are associated with different benefits and risks, which frequently differ according to the patient's baseline clinical profile and risk.

    Risks of patients with ACS

    Risk in ACS refers to the probability of suffering a major negative clinical outcome, most frequently associated with ischaemic recurrences and its clinical correlates, which is known as ischaemic risk. Thus, recurrent ischaemia, need for urgent coronary revascularisation, myocardial infarction, death, and their combinations are the most frequently measured outcomes in ACS risk analysis. However, while some of these outcomes are objective (death) or potentially objective through strict definitions (myocardial infarction), others have a substantial amount of subjectivity in their assessment (recurrent ischaemia requires a clinical judgement to be made of new symptoms or signs, and the need for urgent revascularisation requires a clinical decision making process which is mediated by availability and local policies). For this reason, the former, objective outcomes are called ‘hard endpoints’ and the latter, subjective outcomes are called ‘soft endpoints’.

    The spontaneous risk of ACS to patients depends essentially on local factors, such as the severity of ischaemia, the burden of coronary artery disease, the myocardial mass at risk, the baseline function of the left ventricle, and the patient clinical profile (age, comorbidities, etc). However, this risk changes over time depending on the evolution of the causal factors (progression of coronary thrombosis and obstruction, embolisation, etc), the development of complications, and the response to treatment. Therefore, risk assessment is a dynamic process that starts at the time of first medical contact and changes with clinical evolution and response to treatment, so it needs to be updated over time in order to be accurate.

    Risk assessment is important for the fine calculation of the prognosis of individual patients, which is an important issue not only for communicating with patients and relatives but also for therapeutic decision making. There is strong evidence demonstrating that an aggressive treatment approach has the potential to change the prognosis of patients with ACS, although this effect is frequently risk dependent. Today, it is accepted that high risk ischaemic patients with ACS deserve more aggressive management, including more potent antithrombotic treatment and a rapid invasive strategy, while lower risk patients may do well with less potent antithrombotic treatment and a more selective invasive strategy.w1 w2 Therefore, there is a need to assess ischaemic risk on an individual basis to guide these treatment strategies, tailoring care for each individual patient.

    Several trials have shown that antithrombotic drugs and coronary invasive procedures can reduce the number of ischaemic events in ACS patients, but these treatments usually increase the risk of bleeding. Given that antithrombotic therapies and invasive strategies are key steps in the management of ACS, and that haemorrhages are associated with higher mortality when they are not mild,1–4 the assessment of bleeding risk has become necessary in ACS risk assessment for the calculation of trade-offs between ischaemic risk reduction and spontaneous and treatment related bleeding hazards.

    Risk assessment in ACS patients

    Different ways have been used to stratify risk in ACS patients. Simple risk stratifications have been proposed according to the presence or absence of some key prognostic factors. These include older age, markers of severe ischaemia (positive troponins, dynamic ST segment changes, ischaemic recurrences on adequate treatment), signs of haemodynamic (admission heart rate or systolic blood pressure, shock) or electrical (ventricular arrhythmias) instability, signs of myocardial dysfunction (heart failure, left ventricular dysfunction), comorbidities (diabetes, renal dysfunction, anaemia), and other factors. These simple risk assessment methods were initially recommended by scientific societies to assess risk and select a therapeutic strategy, as they allow an easy qualitative risk classification of high or non-high risk patient groups. However, although risk stratification through single variables is easy when used in a dichotomous fashion (yes/no), and may help in selecting patients with an elevated risk of future adverse cardiovascular events who may benefit from certain therapeutic interventions, such as antiplatelet therapies or early invasive therapies, it does not provide a reliable assessment of risk because it does not allow the absolute risk of individual patients to be estimated. For example, it is not possible to define what is the increase in risk associated with one versus several high risk markers, with the level of troponin elevation in troponin positive patients, with age in older patients, or with diabetes according to its type or duration.

    This lack of accuracy limits the capacity of qualitative risk stratification systems to weigh the individual patient's risk against the potential benefits and risks associated with the use of available interventions, particularly when risks are not placed on the extreme sides of the spectrum (very high, very low).

    Interestingly, many conditions associated with an increased ischaemic risk (eg, advanced age, diabetes, renal failure, anaemia) are also associated with higher bleeding risk. In these cases, the intensity of antithrombotic therapy should be tailored to the individual patient's ischaemic and bleeding risk. However, it is very difficult to make individual decisions on the intensity of antithrombotic therapy when both risks are qualitatively high. Therefore, quantitative risk estimations are more helpful than qualitative risk stratifications in guiding therapy for ACS patients.

    Use of risk scores for ACS

    Risk scores for ischaemic risk assessment

    A number of risk scores have been developed to predict short and mid term outcomes in patients with ACS (table 1).5–15 These scores were created by giving an appropriate number of points for the presence of each risk factor identified by multivariable statistical techniques as an independent predictor of the adverse outcome/s (and with an additive contribution to overall risk), based on the observation of events in specific populations. The number of points given to each component may be proportional to the coefficients obtained in the prognostic model—that is, to their prognostic weight (weighed models)—or they may not relate to their individual prognostic impact (ie, one point for each predictor present). The former use complex formulae to provide continuous risk estimates, while the latter provide stepwise risk estimations according to the number of present predictors (figure 1).

    View this table:
    Table 1

    Predictors of ischaemic or bleeding events in risk scores for patients with acute coronary syndromes

    Figure 1
    Figure 1

    Risk estimation according to the type of risk score. Quantitative risk scores, such as GRACE, PURSUIT, and CRUSADE, use formulae that produce continuous results for the estimation of risk. Semiquantitative risk scores, such as TIMI and FRISC-II, define a number of independent risk predictors. The number of present predictors is associated with a stepwise increase in event risk. For explanation of trial abbreviations, see text.

    One potentially relevant factor for the external validity of risk scores is the population from which they are derived. Models derived from clinical registries enrolling consecutive patients are theoretically more applicable to real life patients than those developed from patients enrolled in clinical trials, which tend to exclude higher risk patients (very old, with important comorbidities).

    Several variables have been associated with higher ischaemic risk in the different scoring systems. These include patient characteristics such as age, gender and body weight, risk factors, antecedents related to a previous history of cardiac or non-cardiac disease, data related to the clinical and haemodynamic presentation, and ECG and laboratory abnormalities. However, there is a limited concordance between models in the selected predictors (table 1). Only age, heart failure, ST segment deviation and elevated cardiac markers were selected as independent risk factors by most predictive models, while a variety of other factors are used in individual models. The most popular risk scoring systems in clinical practice have been the TIMI risk score,8 the GRACE risk scores,5 11 and, to a lesser extent, the PURSUIT risk score.10

    The TIMI (Thrombolysis in Myocardial Infarction) risk score for unstable angina/non-ST elevation myocardial infarction (UA/NSTEMI)8 (not to be confused with the TIMI ST segment elevation AMI risk score) was developed in a derivation cohort consisting of 1957 patients with ACS who were randomised to the unfractionated heparin arm of the TIMI 11B trial; this compared unfractionated heparin with enoxaparin, and initially validated three separate cohorts of patients: the enoxaparin group of the TIMI 11B trial; the group allocated to unfractionated heparin in the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events) trial; and the enoxaparin group from ESSENCE. The TIMI risk score is a simple semiquantitative score that includes seven variables to predict the 14 day risk of the composite end point of death, MI or urgent revascularisation. These seven variables are classified into historical factors: (1) age (<65 or >65 years); (2) ≥3 risk factors for coronary artery disease; (3) known coronary artery disease (stenosis ≥50%); (4) aspirin use in the past 7 days; and presentational factors: (5) recent (≤24 h) severe angina; (6) ST segment deviation ≥0.5 mm; and (7) positive cardiac markers. One point is given for the presence of each predictor so the score ranges from 0 (lowest risk) to 7 (highest risk), which correlate well (c-statistic 0.65) with the selected outcome (14 day incidence of all cause mortality, MI, and severe recurrent ischaemia prompting urgent revascularisation), and mortality (table 2). The TIMI risk score has been validated in populations with ACS from randomised trials,w3 and observational studies for the prediction of in-hospital death,w4 or the composite outcome of death or MI at 28 days.9 The TIMI risk score has also been shown to be useful for clinical decision making as it showed increased benefits with enoxaparinw5 or glycoprotein IIb/IIIa inhibitors in high risk patients,w6 or proved the efficacy of clopidogrel in high risk patients with non-ST elevation ACSw7 after the original publication failed to show such efficacy using the OASIS risk stratification method.w8

    View this table:
    Table 2

    Mortality risk estimations in patients with non-ST-segment elevation acute coronary syndromes according to the GRACE and TIMI risk scores

    The GRACE (Global Registry of Acute Coronary Events) risk score was developed to predict death, and death/MI, in a cohort of 21 688 patients with NSTEMI enrolled into a multinational observational registry. Nine factors based on the presenting clinical and biomarker characteristics of the patients were identified as independent predictors of death or a combined outcome of death and MI both in-hospital5 and at 6 months11: (1) age, (2) heart failure, (3) peripheral vascular disease, (4) admission systolic blood pressure, (5) Killip class, (6) initial serum creatinine concentration, (7) elevated cardiac markers, (8) cardiac arrest on admission, and (9) ST segment deviation. These were incorporated into a continuous model because both age and creatinine value are analysed as continuous variables. The GRACE risk scores have good predictive accuracy both for death (c=0.82) and death/MI (c=0.70) at 6 months and provide quantitative risk estimations through a complex formula. However, due to the complexity of the calculation, this risk score requires specific tools for its use to estimate risk at the bedside. The specific calculator is available at http://www.outcomes-massmed.org/grace/acs_risk/acs_risk_content.html. Interestingly, although precise estimates can be obtained, three risk categories have been developed according to the GRACE risk score results for low, intermediate, and high risk patients (table 2).

    The ability of the GRACE risk score to predict death at different time points has been assessed in several ACS patient cohort registries in the UK, Canada, Portugal, Spain, and New Zealand.w9–w16 Moreover, its clinical utility in selecting patients for a specific therapy has also been validated, both retrospectively in clinical trials (such as for determining the difference in efficacy and safety between fondaparinux and enoxaparin according to patient riskw17) and in observational studies (showing the benefit of an early invasive strategy restricted to higher risk patientsw18), and prospectively, such as in the TIMACS (Timing of Intervention in Acute Coronary Syndromes) trial. The TIMACS trial compared a routine early intervention (coronary angiography ≤24 h after randomisation) with more delayed intervention (coronary angiography ≥36 h after randomisation) in patients with non-ST elevation ACS; it showed that those patients at the highest risk tertile (GRACE risk score >140) improved their primary outcome with an early intervention (hazard ratio (HR) 0.65, 95% CI 0.48 to 0.89), while those patients at low-to-intermediate risk obtained no benefit (HR 1.12, 95% CI 0.81 to 1.56).w19

    The PURSUIT risk score10 was developed from the 9461 patients enrolled in the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, which tested the efficacy of eptifibatide versus placebo in patients with ACS. This quantitative risk score estimates the absolute risk of 30 day death or death/MI based on age, heart rate, systolic blood pressure on admission, ST segment depression, signs of heart failure, and positive cardiac enzymes. It showed a better accuracy to predict death (c=0.81) than to predict death/MI (c=0.67). The PURSUIT score has been validated in populations in the USA,w20 Portugal,w15 and Canada,w11 where it showed high discriminative power, but poor calibration. It allows separate risk stratification of patients with unstable angina and NSTEMI. However, it is a complex model that needs a specific tool for calculations and it is not frequently used.

    The FRISC II risk score13 was developed for 2457 patients with unstable coronary artery disease from the FRISC (Fast Revascularisation During Instability in Coronary Artery Disease) II trial (randomised trial comparing an early invasive vs a non-invasive strategy). Seven factors—age >70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein)—were associated with an independent increased risk for death or death/MI at 1 year. The FRISC II risk score has the merit of being the first one to show the clinical benefit of a therapeutic intervention in a specific subset of patients according to risk. Thus, the FRISC II trial demonstrated a reduction in mortality with an invasive strategy in patients with ≥5 of the score risk factors (5.2% vs 15.4%; relative risk (RR) 0.34, 95% CI 0.15 to 0.78), and a reduction of death/MI in those patients with 3–4 factors (10.8% vs 15.7%; RR 0.69, 95% CI 0.50 to 0.94), while no benefit was observed with the invasive strategy in patients with 0–2 risk factors.w21

    Some other risk scores have been developed but their use is not as common as the previous ones. A comprehensive review of the characteristics and merits of each of these risk scores for ACS has been published by the National Institute for Health and Clinical Excellence (NICE) in the UK.16

    Risk scores for bleeding risk assessment

    The clinical relevance of bleeding in patients with ACS has been identified in the last 10 years.1–4 There has been growing interest in identifying the predictors of bleeding, particularly major bleeding.1 Some attempts have been performed recently to quantitatively assess the risk of major bleeding. For this purpose, two risk scores have been produced.

    The first bleeding risk score was developed in 71 277 patients with NSTEMI enrolled in the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) US Quality Improvement Initiative. The CRUSADE bleeding score14 assigned weighted integers that corresponded to the coefficient of each variable to the outcome of in-hospital major bleeding. The model identified eight independent baseline predictors (baseline haematocrit <36%, creatinine clearance, heart rate, female sex, signs of congestive heart failure at presentation, systolic blood pressure (SBP) ≤110 mm Hg, SBP ≥180 mm Hg, prior vascular disease, and diabetes mellitus) with which a score ranging from 1 to 100 points identified the risk of major bleeding during hospitalisation. The rate of major bleeding increased by bleeding risk score quintiles: from 3.1% for those at very low risk (score ≤20) to 19.5% for those at very high risk (score ≥50). The model was validated in a second cohort of 17 857 CRUSADE patients, finding a similar predictive accuracy according to post-admission management (invasive or conservative approach, more intensive or less intensive antithrombotic therapy). It has also been validated in one Spanish cohort of patients with ACS.w22

    Mehran et al published an integer risk score for major bleeding in ACS15 developed from a multivariable logistic regression model derived from 17 421 patients enrolled in two clinical trials testing bivalirudin as an anticoagulant for non-ST segment elevation ACS and ST segment elevation MI: the ACUITY (Acute Catheterisation and Urgent Intervention Triage strategY) trial; and the HORIZONS-AMI (Harmonising Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction) trial. Seven independent predictors, six baseline factors (female sex, advanced age, elevated serum creatinine, white blood cell count, anaemia, type of MI) and one treatment related variable (use of heparin plus a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) discriminated patients with different 30 day rates of non-coronary artery bypass graft surgery related TIMI defined major bleeding, ranging from 1% to over 40%. External validation of this risk score is not available to date.

    What risk score should be used?

    Quantitative risk scores may be able to estimate risk more accurately than simple risk scores, but they are also more difficult to calculate as they incorporate continuous variables and need complex formulae to obtain their results. For that, online calculators and applications for PDA (personal digital assistant) devices have been developed, but considerable resistance to their incorporation into routine practice remains.

    Some studies have compared face to face the performance of different risk scores, mainly the TIMI and GRACE risk scores.w11 w15 w23 NICE in the UK systematically compared a variety of scoring systems including TIMI, GRACE, PURSUIT, and others. On the basis of these comparisons, the GRACE risk score is considered to be the one with the highest discriminative power, although the superiority of GRACE has not been attributed to its relative simplicity but rather to the omission of key risk factors by the TIMI risk score.w24

    The 2007 American College of Cardiology/American Heart Association guidelines for the management of ACS recommended the use of one validated risk score, mentioning the TIMI, GRACE, and PURSUIT risk scores, but showing no preference.w2 The 2007 European Society of Cardiology guidelines for the management of ACS favoured the use of the GRACE risk score over others, acknowledging that the FRISC II score was the only one showing a benefit associated with selection of strategy.w1 The review by NICE compared the discriminative capacity of some of the risk scores to predict short and longer term outcomes in populations with ACS in a cohort of 75 627 patients admitted to hospitals in England and Wales and enrolled in the large MINAP (Myocardial Infarction National Audit Project) dataset. Their conclusion was that none of the risk scores is clearly superior in terms of prognostic value, although PURSUIT, GRACE, and PREDICT seem to have better discrimination than TIMI for mortality.16 Thus, the GRACE score is probably the best predictor of ischaemic risk in patients with ACS, but whether this score should be systematically recommended for all patients is not well defined. In contrast, bleeding risk scores have not been compared so far and no recommendations for their use have been formally established yet.

    Guidelines recommend the use of risk scores for risk assessment and clinical decision making in patients with ACS. The 2007 ESC guidelines for the diagnosis and treatment of non-ST elevation ACS recommended an early invasive strategy in intermediate to high risk patients according to a risk score, or a conservative strategy in low risk patients as assessed by a risk score.w1 The 2011 ACCF-AHA Focused Update of the Guidelines for the Management of NSTEACSw25 recommend an invasive strategy as being preferable in patients with a high risk score (eg, TIMI, GRACE), or not recommending upstream glycoprotein IIb/IIIa inhibitors in UA/NSTEMI patients who are at low risk for ischaemic events (eg, TIMI risk score ≤2).w25 The recently released ESC Guidelines for the management of NSTEACS17 recommend the use of risk scores for stratification of both ischemic and bleeding risk, with a preference for the GRACE and CRUSADE risk scores, respectively. Moreover, an early invasive strategy within 24 h is recommended for patients with a GRACE risk score >140 or with at least one major high risk criterion while for those with a GRACE risk score of <140 but with at least one high risk criterion the invasive evaluation can be delayed without increased risk but should be performed within 72 h of admission.

    Several studies have shown a discordance between a patient's risk and the intensity of their treatment.w18 w26 w27 Indeed, a risk paradox in the management of ACS, with lower risk patients being treated more aggressively than higher risk patients, has been suggested.w28 Whether these limitations in the current management of patients with ACS are due to a suboptimal risk stratification, and whether the systematic application of risk scores will improve patient management and outcomes or reduce costs through the application of available therapies only to the appropriate candidates, remain to be proven.

    Conclusions

    Risk scores are helpful tools for the assessment of risk in ACS patients. Risk scores allow accurate estimations of ischaemic and bleeding risk for individual patients. In addition to its utility in prognosis assessment, this information may be helpful for weighing the patient's risks with the expected benefits and risks associated with available therapies, hence facilitating individual tailoring of treatments. Despite these theoretical advantages, there is a need for stronger evidence showing a benefit associated with the systematic use of risk scores on optimising therapies, reducing costs or improving patient outcomes. More research is needed to address the impact of the use of risk stratification systems, and particularly of risk scores, on practice patterns and patient outcomes as well as the most effective ways to increase their use in routine clinical practice.w29

    You can get CPD/CME credits for Education in Heart

    Education in Heart articles are accredited by both the UK Royal College of Physicians (London) and the European Board for Accreditation in Cardiology—you need to answer the accompanying multiple choice questions (MCQs). To access the questions, click on BMJ Learning: Take this module on BMJ Learning from the content box at the top right and bottom left of the online article. For more information please go to: http://heart.bmj.com/misc/education.dtl

    ▶ RCP credits: Log your activity in your CPD diary online (http://www.rcplondon.ac.uk/members/CPDdiary/index.asp)—pass mark is 80%.

    ▶ EBAC credits: Print out and retain the BMJ Learning certificate once you have completed the MCQs—pass mark is 60%. EBAC/ EACCME Credits can now be converted to AMA PRA Category 1 CME Credits and are recognised by all National Accreditation Authorities in Europe (http://www.ebac-cme.org/newsite/?hit=men02).

    Please note: The MCQs are hosted on BMJ Learning—the best available learning website for medical professionals from the BMJ Group. If prompted, subscribers must sign into Heart with their journal's username and password. All users must also complete a one-time registration on BMJ Learning and subsequently log in (with a BMJ Learning username and password) on every visit.

    Key prognostic factors of ischaemic risk in acute coronary syndromes

    • Older age

    • Male gender

    • Diabetes

    • Renal failure

    • Anaemia

    • Prior vascular/coronary artery disease

    • Heart failure (past, or present)

    • Haemodynamics on presentation (systolic blood pressure, heart rate)

    • Clinical instability (shock, ventricular arrhythmias)

    • ST segment deviation

    • Elevated cardiac biomarkers

    Key prognostic factors for major bleeding risk in acute coronary syndromes

    • Older age

    • Female gender

    • Renal failure

    • Diabetes

    • Anaemia

    • History of bleeding

    • ST segment deviation

    • Elevated cardiac biomarkers

    • Invasive cardiac interventions

    • Intensity of antithrombotic treatment (number of drugs, excess dosing)

    References

    1. ↵
      1. Moscucci M,
      2. Fox KA,
      3. Cannon CP,
      4. et al
      . Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2003;24:1815–23.
      OpenUrlAbstract/FREE Full Text
      First major study on predictors of major bleeding in patients with ACS.
    2. ↵
      1. Rao SV,
      2. O'Grady K,
      3. Pieper KS,
      4. et al
      . Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol 2005;96:1200–6.
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      1. Eikelboom JW,
      2. Mehta SR,
      3. Anand SS,
      4. et al
      . Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006;114:774–82.
      OpenUrlAbstract/FREE Full Text
    4. ↵
      1. Mehran R,
      2. Pocock SJ,
      3. Stone GW,
      4. et al
      . Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial. Eur Heart J 2009;30:1457–66.
      OpenUrlAbstract/FREE Full Text
      A study showing how major bleeding in patients with ACS carries a prognosis as poor as a new MI in terms of mortality.
    5. ↵
      1. Granger CB,
      2. Goldberg RJ,
      3. Dabbous O,
      4. et al
      . Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 2003;163:2345–53.
      OpenUrlCrossRefPubMedWeb of Science
      First study of the GRACE risk scores for ACS patients, this one predicting in-hospital mortality or death/MI.
    6. ↵
      1. Kurz DJ,
      2. Bernstein A,
      3. Hunt K,
      4. et al
      . Simple point-of-care risk stratification in acute coronary syndromes: the AMIS model. Heart 2009;95:662–8.
      OpenUrlAbstract/FREE Full Text
    7. ↵
      1. Piombo AC,
      2. Gagliardi JA,
      3. Guetta J,
      4. et al
      . A new scoring system to stratify risk in unstable angina. BMC Cardiovas Disord 2003;3:8.
      OpenUrlCrossRef
    8. ↵
      1. Antman EM,
      2. Cohen M,
      3. Bernink PJ,
      4. et al
      . The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000;284:835–42.
      OpenUrlCrossRefPubMedWeb of Science
      Presentation of the TIMI risk score for ACS, one of the most popular systems used internationally to estimate ischaemic risk.
    9. ↵
      1. Singh M,
      2. Reeder GS,
      3. Jacobsen SJ,
      4. et al
      . Scores for post-myocardial infarction risk stratification in the community. Circulation 2002;106:2309–14.
      OpenUrlAbstract/FREE Full Text
    10. ↵
      1. Boersma E,
      2. Pieper KS,
      3. Steyerberg EW,
      4. et al
      . Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation 2000;101:2557–67.
      OpenUrlAbstract/FREE Full Text
      Presentation of the PURSUIT score, the first quantitative risk score for ACS.
    11. ↵
      1. Fox KAA,
      2. Dabbous OH,
      3. Goldberg RJ,
      4. et al
      . Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 2006;333:1091.
      OpenUrlAbstract/FREE Full Text
      GRACE risk score for death or death/MI at 6 months.
    12. ↵
      1. Mahaffey KW,
      2. Yang Q,
      3. Pieper KS,
      4. et al
      . Prediction of one-year survival in high-risk patients with acute coronary syndromes: results from the SYNERGY trial. J Gen Intern Med 2008;23:310–16.
      OpenUrlCrossRefPubMedWeb of Science
    13. ↵
      1. Lagerqvist B,
      2. Diderholm E,
      3. Lindahl B,
      4. et al
      . FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease. Heart 2005;91:1047–52.
      OpenUrlAbstract/FREE Full Text
      The FRISC II risk score showed not only that it could accurately estimate mortality risk in ACS patients but that it could define the group of patients who benefit most from an early invasive strategy.
    14. ↵
      1. Subherwal S,
      2. Bach RG,
      3. Chen AY,
      4. et al
      . Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation 2009;119:1873–82.
      OpenUrlAbstract/FREE Full Text
      First risk score for major bleeding in ACS patients, derived from the large US CRUSADE registry.
    15. ↵
      1. Mehran R,
      2. Pocock SJ,
      3. Nikolsky E,
      4. et al
      . A risk score to predict bleeding in patients with acute coronary syndromes. J A Coll Cardiol 2010;55:2556–66.
      OpenUrlCrossRef
    16. ↵
      National Institute for Health and Clinical Excellence. Unstable angina and NSTEMI: the early management of unstable angina and non-ST-segment-elevation myocardial infarction. London: NICE, 2010. http://www.nice.org.uk/nicemedia/live/12949/47921/47921.pdf
      The chapter “Risk assessment” of this document is a must-read for anyone interested in risk assessment and particularly in risk scores for ACS patients. There is a comprehensive comparison of the performances of the most important risk scores developed for ACS patients.
    17. ↵
      1. Hamm CW,
      2. Bassand JP,
      3. Agewall S,
      4. et al
      . ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011 Sep 21.
      First guidelines recommending the assessment of ischemic and bleeding risk through risk scores (GRACE and CRUSADE), and changing management recommendations according to risk scores results (invasive strategy within 24 hours for patients with GRACE risk score > 140) in patients with NSTEACS.
    View Abstract

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

      Files in this Data Supplement:

    Footnotes

    • Competing interests In compliance with EBAC/EACCME guidelines, all authors participating in Education in Heart have disclosed potential conflicts of interest that might cause a bias in the article. The authors have no competing interests.

    • Provenance and peer review Commissioned; internally peer reviewed.