| ESC Pocket Guidelines |
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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)
* Adapted from the ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (European Heart Journal (2011) 32, 2999-3054 - doi:10.1093/eurheartj/ehr236)
To read the full report as published by the European Society of Cardiology, visit our web site at www.escardio.org/guidelines
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)
Chairpersons
Task Force Members
Stefan Agewall, Oslo, Norway;
Jeroen Bax, Leiden, The Netherlands;
Eric Boersma, Rotterdam, The Netherlands;
Hector Bueno, Madrid, Spain;
Pio Caso, Naples, Italy;
Dariusz Dudek, Krakow, Poland;
Stephan Gielen, Leipzig, Germany;
Kurt Huber, Vienna, Austria;
Magnus Ohman, Durham, USA;
Mark C. Petrie, Glasgow, UK;
Frank Sonntag, Henstedt-Ulzburg, Germany;
Miguel Sousa Uva, Lisbon, Portugal;
Robert F. Storey, Sheffield, UK;
William Wijns, Aalst, Belgium;
Doron Zahger, Beer Sheva, Israel.
Other ESC entities having participated in the development of this document:
Associations: Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
Working Groups: Cardiovascular Pharmacology and Drug Therapy, Thrombosis, Cardiovascular Surgery, Acute Cardiac Care, Atherosclerosis and Vascular Biology, Coronary Pathophysiology and Microcirculation.
Councils: Cardiovascular Imaging, Cardiology Practice
Cyril Moulin, Veronica Dean, Catherine Després, Nathalie Cameron - Sophia Antipolis, France
Special thanks to Bogdan A. Popescu for his valuable contribution
More:
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Recommendations for:
List of Acronyms and Abbreviations
Cardiovascular diseases are the leading cause of death in industrialized countries and are expected to become so in emerging countries by 2020. Among these, coronary artery disease (CAD) is the most prevalent manifestation and is associated with high mortality and morbidity. The clinical presentations of CAD include silent ischaemia, stable angina pectoris, unstable angina, myocardial infarction, heart failure, and sudden death. Patients with chest pain represent a very substantial proportion of all acute medical hospitalizations in Europe.
The present document deals with the management of patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS), replacing the document published in 2007. The management of patients with ST-elevation MI (STEMI) is addressed in the respective ESC Guidelines.
| Classes of Recommendations | |
|---|---|
| Classes of Recommendations | Definition |
| Class I | Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure. |
| Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy. |
| Class IIb | Usefulness/efficacy is less well established by evidence/opinion. |
| Class III | Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful. |
| Level of Evidence | |
|---|---|
| Level of Evidence A | Data derived from multiple randomized clinical trials or meta-analyses. |
| Level of Evidence B | Data derived from a single randomized clinical trial or large non-randomized studies. |
| Level of Evidence C | Consensus of opinion of the experts and/or small studies, retrospective studies, registries. |
The leading symptom that initiates the diagnostic and therapeutic cascade is chest pain, but the classification of patients is based on the electrocardiogram (ECG). Two categories of patients may be encountered:
1. Patients with acute chest pain and persistent (>20 min) ST-segment elevation.
This is termed ST-elevation ACS (STE-ACS) and generally reflects an acute total coronary occlusion. Most of these patients will ultimately develop an STEMI. The therapeutic objective is to achieve rapid, complete, and sustained reperfusion by primary angioplasty or fibrinolytic therapy.
2. Patients with acute chest pain but without persistent ST-segment elevation.
These patients have rather persistent or transient ST-segment depression or T-wave inversion, flat T waves, pseudo-normalization of T waves, or no ECG changes at presentation. The initial strategy in these patients is to alleviate ischaemia and symptoms, to monitor the patient with serial ECGs, and to repeat measurements of markers of myocardial necrosis. At presentation, the working diagnosis of NSTE-ACS, based on the measurement of troponins, will be further qualified as non-ST-elevation MI (NSTEMI) or unstable angina (Figure 1). In some patients, coronary heart disease will subsequently be excluded as the cause of symptoms.
Distinguishing patients with ACS within the very large proportion with suspected cardiac pain represents a diagnostic challenge, especially in individuals without clear symptoms or electrocardiographic features. Despite modern treatment, the rates of death, MI, and readmission of patients with ACS remain high.
The leading symptom of ACS is typically chest pain. The working diagnosis of NSTE-ACS is a rule-out diagnosis based on the ECG, i.e. lack of persistent ST elevation. Biomarkers (troponins) further distinguish NSTEMI and unstable angina. Imaging modalities are used to rule-out or rule-in differential diagnoses. Diagnosis findings and risk stratification are closely linked.
The clinical presentation of NSTE-ACS encompasses a wide variety of symptoms. The typical clinical presentation of NSTE-ACS is retrosternal pressure or heaviness ('angina') radiating to the left arm, neck or jaw, which may be intermittent (usually lasting for several minutes) or persistent.
These complaints may be accompanied by other symptoms such as diaphoresis, nausea, abdominal pain, dyspnoea, and syncope. However, atypical presentations are not uncommon. These include epigastric pain, indigestion, stabbing chest pain, chest pain with some pleuritic features, or increasing dyspnoea. Atypical complaints are more often observed in older (>75 years) patients, in women, and in patients with diabetes, chronic renal failure, or dementia. Absence of chest pain leads to under-recognition and under-treatment of the disease.
Traditionally, several clinical presentations have been distinguished:
Physical examination: The physical examination is frequently normal. Signs of heart failure or haemodynamic instability must prompt the physician to expedite diagnosis and treatment. An important goal of the physical examination is to exclude non-cardiac causes of chest pain and non-ischaemic cardiac disorders (e.g. pulmonary embolism, aortic dissection, pericarditis, valvular heart disease) or potentially extra-cardiac causes such as acute pulmonary diseases (e.g. pneumothorax, pneumonia, pleural effusion).
ECG: The resting 12-lead ECG is the first-line diagnostic tool in the assessment of patients with suspected NSTE-ACS. It should be obtained within 10 min after first medical contact and immediately interpreted by a qualified physician. The characteristic ECG abnormalities of NSTE-ACS are ST-segment depression or transient elevation and/or T-wave changes. The finding of persistent (>20 min) ST-elevation suggests STEMI, which mandates different treatment.
Biomarkers: Cardiac troponins play a central role in establishing a diagnosis and stratifying risk, and make it possible to distinguish between NSTEMI and unstable angina. Troponins are more specific and sensitive than the traditional cardiac enzymes such as creatine kinase (CK) or its isoenzyme MB (CK-MB). A test with high ability to rule out (negative predictive value) and correctly diagnose ACS (positive predictive value) is of paramount interest. The diagnostic cut-off for MI is defined as a cardiac troponin measurement exceeding the 99th percentile of a normal reference population (upper reference limit) using an assay with an imprecision (coefficient of variation) of ≤10% at the upper reference limit. In NSTE-ACS, minor troponin elevations usually resolve within 48-72 h. There is no fundamental difference between troponin T and troponin I. With recently introduced high-sensitivity assays MI can be detected more frequently and earlier in patients presenting with chest pain allowing a rapid rule-out protocol (3 hours). In order to differentiate chronic from acute troponin elevation the magnitude of change depending on the initial value gains importance at borderline levels (Figure 2).
Other biomarkers are helpful for differential diagnoses: d-dimer (pulmonary embolism), BNP/NT-proBNP (dyspnoea, heart failure), haemoglobin (anaemia), leucocytes (inflammatory disease), markers of renal function.
| Table 1: Possible non-ACS causes of troponin elevation |
|---|
| · Chronic or acute renal dysfunction |
| · Severe congestive heart failure - acute and chronic |
| · Hypertensive crisis |
| · Tachy- or bradyarrhythmias |
| · Pulmonary embolism, severe pulmonary hypertension |
| · Inflammatory diseases, e.g. myocarditis |
| · Acute neurological disease, including stroke, or subarachnoid haemorrhage |
| · Aortic dissection, aortic valve disease, or hypertrophic cardiomyopathy |
| · Cardiac contusion, ablation, pacing, cardioversion, or endomyocardial biopsy |
| · Hypothyroidism |
| · Apical ballooning syndrome (Tako-Tsubo cardiomyopathy) |
| · Infiltrative diseases, e.g. amyloidosis, haemochromatosis, sarcoidosis, sclerodermia |
| · Drug toxicity, e.g. adriamycin, 5-fluorouracil, herceptin, snake venoms |
| · Burns, if affecting >30% of body surface area |
| · Rhabdomyolysis |
| · Critically ill patients, especially with respiratory failure, or sepsis |
3.3 NSTE-ACS differential diagnoses
| Table 2: Cardiac and non-cardiac conditions that can mimic NSTE-ACS | |
|---|---|
| Cardiac |
Myocarditis
Pericarditis Cardiomyopathy Valvular disease Tako-Tsubo cardiomyopathy Cardiac trauma |
| Pulmonary |
Pulmonary embolism
Pulmonary infarction Pneumonia Pleuritis Pneumothorax |
| Haematological |
Sickle cell crisis
Anaemia |
| Vascular |
Aortic dissection
Aortic aneurysm Cerebrovascular disease |
| Gastrointestinal |
Oesophageal spasm
Oesophagitis Peptic ulcer Pancreatitis Cholecystitis |
| Orthopaedic / infectious |
Cervical discopathy
Rib fracture Muscle injury/inflammation Costochondritis Herpes zoster |
NSTE-ACS is an unstable coronary condition prone to ischaemic recurrences and other complications that may lead to death or MI in the short and long term. The management, which includes anti-ischaemic and antithrombotic pharmacological treatments as well as various strategies for coronary revascularization, is directed to prevent or reduce such complications and to improve outcomes.
In addition to clinical markers of risk, such as advanced age, diabetes, renal failure, or other co-morbidities, the initial clinical presentation is highly predictive of early prognosis. Symptoms at rest carry a worse prognosis than symptoms elicited only during physical exertion. In patients with intermittent symptoms, an increasing number of episodes preceding the index event also has an impact on outcome. The presence of tachycardia, hypotension, or heart failure upon presentation indicates a poor prognosis and calls for rapid diagnosis and management.
4.2 Electrocardiogram indicators
The initial ECG presentation is predictive of early risk. The number of leads showing ST depression and the magnitude of ST-depression are indicative of extent and severity of ischaemia and correlate with prognosis. ST-segment depression ≥ 0.5 mm (0.05 mV) in two or more contiguous leads, in the appropriate clinical context, is suggestive of NSTE- ACS and linked to prognosis. Minor (0.5 mm) ST-depression may be difficult to measure in clinical practice. More relevant is ST-depression of ≥ 1mm (0.1 mV), and particularly ST-depression of ≥ 2 mm. ST-depression combined with transient ST-elevation also identifies a high risk subgroup. Deep symmetrical inversion of the T-waves in the anterior chest leads is often related to a significant stenosis of the proximal left anterior descending coronary artery or main stem. Continuous ST-segment monitoring adds independent prognostic information to that provided by the ECG at rest, troponins, and other clinical variables.
Biomarkers reflect different pathophysiological aspects of NSTE-ACS, such as myocardial cell injury, inflammation, platelet activation, and neurohormonal activation. Troponin T or I are the preferred biomarkers to predict short-term (30 days) outcome with respect to MI and death. The prognostic value of troponin measurements has also been confirmed for the long term (1 year and beyond). Any troponin elevation is associated with an adverse prognosis.
NSTEMI patients with elevated troponin levels but no rise in CK-MB (who comprise approximately one third of the NSTEMI population), although undertreated, have a higher-risk profile and lower in-hospital mortality than patients with both markers elevated. The increased risk associated with elevated troponin levels is independent of and additive to other risk factors, such as ECG changes at rest or on continuous monitoring, or markers of inflammatory activity. Furthermore, the identification of patients with elevated troponin levels is also useful for selecting appropriate treatment in patients with NSTE-ACS. However, troponins should not be used as sole decision criterion, because in-hospital mortality may be high in certain high-risk troponin-negative subgroups
Due to low sensitivity for MI, a single negative test on first contact with the patient is not sufficient for ruling out NSTE-ACS, as in many patients an increase in troponins can be detected only in the subsequent hours. Therefore, repeated measurements after 6-9 h have been advocated. The recently introduced high sensitivity troponin assays better identify patients at risk and provide reliable and rapid prognosis prediction allowing a fast track rule-out protocol (3 h). For further details, see Section 3.2 and Figure 2.
While cardiac troponins are the key biomarkers for initial risk stratification, multiple other biomarkers have been evaluated for incremental prognostic information. Natriuretic peptides such as BNP or its N-terminal prohormone fragment (NT-proBNP) are highly sensitive and fairly specific markers for the detection of LV dysfunction. Accordingly, they are useful markers in the emergency room in evaluating chest pain or dyspnoea and were shown to be helpful in differentiating cardiac and non-cardiac causes of dyspnoea. In NSTE-ACS, patients with elevated BNP or NT-proBNP levels have a three- to fivefold increased mortality rate when compared to those with lower levels independent of troponin and hsCRP measurements. The level is strongly associated with the risk of death even when adjusted for age, Killip class, and LV ejection fraction. However, as markers of long-term prognosis, they have limited value for initial risk stratification and hence for selecting the initial therapeutic strategy in NSTE-ACS.
Of the numerous inflammatory markers investigated over the past decade, CRP measured by high-sensitivity (hsCRP) assays is the most widely studied and is linked to adverse events. There is solid evidence that even among patients with troponin-negative NSTE-ACS, elevated levels of hsCRP (>10 mg/L) are predictive of long-term mortality (>6 months up to 4 years). Patients with persistently elevated hsCRP levels carry the highest risk. However, hsCRP has no role for the diagnosis of ACS.
Hyperglycaemia on admission is a strong predictor of mortality and heart failure even in non-diabetic patients. More recently it became apparent that fasting glucose levels, obtained early during the hospital course, may predict mortality even better than admission levels.
Furthermore, fluctuations of fasting glucose during hospital stay are strongly predictive of outcome and persistently abnormal fasting glucose levels carry a particularly ominous prognosis.
A number of routine haematological variables are also predictors of worse prognosis. Patients with anaemia have consistently been shown to be at higher risk. Similarly, higher white blood cell counts or lower platelet counts on admission are associated with worse outcomes.
Impaired renal function is a strong independent predictor of long-term mortality in ACS patients. Serum creatinine concentration is a less reliable indicator of renal function than creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) because it is affected by a multitude of factors including age, weight, muscle mass, race, and various medications. Several formulae have been devised to improve the accuracy of serum creatinine level as a surrogate for eGFR, including the Cockcroft-Gault and the abbreviated Modification of Diet in Renal Disease (MDRD) equations. Long-term mortality increases exponentially with decreasing eGFR/CrCl.
Quantitative assessment of risk is useful for clinical decision-making. Several scores have been developed from different populations to estimate ischaemic and bleeding risks, with different outcomes and time frames. In clinical practice simple risk scores may be more convenient and preferred.
Risk scores of outcome
Among several risk scores predicting short- or mid-term risk of ischaemic events, the GRACE and the TIMI risk scores are the most widely used. There are some differences with respect to populations, outcomes, and time frames, as well as predictors derived from baseline characteristics, history, clinical or haemodynamic presentation, ECG, laboratory measures, and treatment. The GRACE risk score provides the most accurate stratification of risk both on admission and at discharge due to its good discriminative power (Table 3).
However, the complexity of the estimation requires the use of computer or personal digital assistant software for risk calculations, which can also be performed online (http://www.outcomes.org/grace).
| Table 3: Mortality in hospital and at 6 months in low-, intermediate-, and high-risk categories in registry populations, according to the GRACE risk score | ||
|---|---|---|
| Risk category (tertile) | GRACE risk score | In-hospital death (%) |
| Low | ≤108 | <1 |
| Intermediate | 109-140 | 1-3 |
| High | >140 | >3 |
| Risk category (tertile) | GRACE risk score | Post-discharge to 6-month death (%) |
| Low | ≤88 | <3 |
| Intermediate | 89-118 | 3-8 |
| High | >118 | >8 |
Bleeding risk scores
Bleeding is associated with an adverse prognosis in NSTE-ACS and all efforts should be made to reduce bleeding whenever possible. A few variables can help to classify patients into different levels of risk for major bleeding during hospitalization. Bleeding risk scores have been developed from registry or trial cohorts in the setting of ACS and PCI.
The CRUSADE bleeding risk score (www.crusadebleedingscore.org/) was developed from a large cohort from the CRUSADE registry (derivation cohort) and further validated in a validation cohort from the same registry (Table 4). The rate of major bleeding increased gradually with rising bleeding risk score (Figure 3). This score has relatively high accuracy for estimating bleeding risk by incorporating admission and treatment variables. In this bleeding risk score, age is not listed among the predictors, but is contained in the creatinine clearance calculation.
| Table 4: CRUSADE registry bleeding risk score | |
|---|---|
| Algorithm used to determine the risk score of CRUSADE In-Hospital major bleeding | |
| See Notes | |
| Predictor | Score |
| Baseline haematocrit, % | |
| <31 | 9 |
| 31-33.9 | 7 |
| 34-36.9 | 3 |
| 37-39.9 | 2 |
| ≥40 | 0 |
| Creatinine clearance, mL/min
creatinine clearance was estimated with the Cockcroft-Gault formula. |
|
| ≤15 | 39 |
| >15-30 | 35 |
| >30-60 | 28 |
| >60-90 | 17 |
| >90-120 | 7 |
| >120 | 0 |
| Heart rate (b.p.m.) | |
| ≤70 | 0 |
| 71-80 | 1 |
| 81-90 | 3 |
| 91-100 | 6 |
| 101-110 | 8 |
| 111-120 | 10 |
| ≥121 | 11 |
| Sex | |
| Male | 0 |
| Female | 8 |
| Signs of CHF at presentation | |
| No | 0 |
| Yes | 7 |
| Prior vascular disease
Prior vascular disease was defined as history of peripheral artery disease or prior stroke. |
|
| No | 0 |
| Yes | 6 |
| Diabetes mellitus | |
| No | 0 |
| Yes | 6 |
| Systolic blood pressure, mmHg | |
| ≤90 | 10 |
| 91-100 | 8 |
| 101-120 | 5 |
| 121-180 | 1 |
| 181-200 | 3 |
| ≥201 | 5 |
Used with permission from Subherwal S et al; Circulation 2009; 119:1873-1882.
CHF = congestive heart failure;
CRUSADE = Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines.
In addition to the early risk factors, a number of other factors are associated with long-term risk over many years of follow-up. These are important for refining early risk stratification on top of established risk scores, and may lead to the intensification of the initial therapeutic and interventional strategy. Such factors include a complicated clinical course, LV systolic function, severity of CAD, revascularization status, and evidence of residual ischaemia on non-invasive testing.
| Recommendations for diagnosis and risk stratification | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| In patients with a suspected NSTE-ACS, diagnosis and short-term ischaemic/bleeding risk stratification should be based on a combination of clinical history, symptoms, physical findings, ECG (repeated or continuous ST monitoring), and biomarkers. | I | A |
| ACS patients should be admitted preferably to dedicated chest pain units or coronary care units. | I | C |
| It is recommended to use established risk scores for prognosis and bleeding (e.g. GRACE, CRUSADE). | I | B |
| A 12-lead ECG should be obtained within 10 min after first medical contact and immediately read by an experienced physician. This should be repeated in the case of recurrence of symptoms, and after 6-9 and 24 h, and before hospital discharge. | I | B |
| Additional ECG leads (V3R and V4R, V7-V9) are recommended when routine leads are inconclusive. | I | C |
| Blood has to be drawn promptly for troponin (cardiac troponin T or I) measurement. The result should be available within 60 min. The test should be repeated 6-9 h after initial assessment if the first measurement is not conclusive. Repeat testing after 12-24 h is advised if the clinical condition is still suggestive of ACS. | I | A |
| A rapid rule-out protocol (0 and 3 h) is recommended when highly sensitive troponin tests are available (see Figure 2). | I | B |
| An echocardiogram is recommended for all patients to evaluate regional and global LV function and to rule in or rule out differential diagnoses. | I | C |
| Coronary angiography is indicated in patients in whom the extent of CAD or the culprit lesion has to be determined (see Section 5.4). | I | C |
| Coronary CT angiography should be considered as an alternative to invasive angiography to exclude ACS when there is a low to intermediate likelihood of CAD and when troponin and ECG are inconclusive. | IIa | B |
| In patients without recurrence of pain, normal ECG findings, negative troponins tests, and a low risk score, a non-invasive stress test for inducible ischaemia is recommended before deciding on an invasive strategy. | I | A |
ACS = acute coronary syndromes;
CAD = coronary artery disease;
CRUSADE = Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines;
CT = computed tomography;
ECG = electrocardiogram;
GRACE = Global Registry of Acute Coronary Events;
NSTE-ACS = non-ST-segment elevation acute coronary syndrome.
Anti-ischaemic drugs either decrease myocardial oxygen demand (by decreasing heart rate, lowering blood pressure, reducing preload, or reducing myocardial contractility) or increase myocardial oxygen supply (by inducing coronary vasodilatation).
Available anti-ischaemic drugs for the treatment of NSTE-ACS are nitrates, beta-blockers, and calcium channel antagonists.
| Recommendations for anti-ischaemic drugs | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Oral or intravenous nitrate treatment is indicated to relieve angina; intravenous nitrate treatment is recommended in patients with recurrent angina and/or signs of heart failure. | I | C |
| Patients on chronic β-blocker therapy admitted with ACS should be continued on β-blocker therapy if not in Killip class ≥III. | I | B |
| Oral β-blocker treatment is indicated in all patients with LV dysfunction (see Section 5.5) without contraindications. | I | B |
| Calcium channel blockers are recommended for symptom relief in patients already receiving nitrates and β-blockers (dihydropyridines type), and in patients with contraindications to β-blockade (benzothiazepine or phenylethylamine type). | I | B |
| Calcium channel blockers are recommended in patients with vasospastic angina. | I | C |
| Intravenous β-blocker treatment at the time of admission should be considered for patients in a stable haemodynamic condition (Killip class <III) with hypertension and/or tachycardia. | IIa | C |
| Nifedipine, or other dihydropyridines, are not recommended unless combined with β-blockers. | III | B |
ACS = acute coronary syndrome;
LV = left ventricular.
Platelet activation and subsequent aggregation play a dominant role in the propagation of arterial thrombosis and consequently are the key therapeutic targets in the management of ACS.
Antiplatelet therapy should be instituted as early as possible when the diagnosis of NSTE-ACS is made in order to reduce the risk of both acute ischaemic complications and recurrent atherothrombotic events.
Platelets can be inhibited by three classes of drugs: aspirin, P2Y12 inhibitors, and glycoprotein IIb/IIIa inhibitors.
| Table 5: P2Y12-inhibitors | |||
|---|---|---|---|
| Clopidogrel | Prasugrel | Ticagrelor | |
| Class | Thieno- pyridine |
Thieno- pyridine |
Triazolo- pyrimidine |
| Reversibil- ity |
Irrevers- ible |
Irrevers- ible |
Reversible |
| Activation | Prodrug, limited by metaboliz- ation |
Prodrug, not limited by metaboliz- ation |
Active drug |
| Onset of effect*
*50% inhibition of platelet aggregation |
2-4 h | 30 min | 30 min |
| Duration of effect | 3-10 days | 5-10 days | 3-4 days |
| Withdrawal before major surgery | 5 days | 7 days | 5 days |
| Recommendations for oral antiplatelet agents | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Aspirin should be given to all patients without contraindications at an initial loading dose of 150-300 mg, and at a maintenance dose of 75-100 mg daily long-term regardless of treatment strategy. | I | A |
| A P2Y12 inhibitor should be added to aspirin as soon as possible and maintained over 12 months, unless there are contraindications such as excessive risk of bleeding. | I | A |
| A proton pump inhibitor (preferably not omeprazole) in combination with DAPT is recommended in patients with a history of gastrointestinal haemorrhage or peptic ulcer, and appropriate for patients with multiple other risk factors (H. elicobacter pylori infection, age ≥65 years, concurrent use of anticoagulants or steroids). | I | A |
| Prolonged or permanent withdrawal of P2Y12 inhibitors within 12 months after the index event is discouraged unless clinically indicated. | I | C |
| Ticagrelor (180-mg loading dose, 90 mg twice daily) is recommended for all patients at moderate-to-high risk of ischaemic events (e.g. elevated troponins), regardless of initial treatment strategy and including those pre-treated with clopidogrel (which should be discontinued when ticagrelor is commenced). | I | B |
| Prasugrel (60-mg loading dose, 10-mg daily dose) is recommended for P2Y12-inhibitor-naïve patients (especially diabetics) in whom coronary anatomy is known and who are proceeding to PCI unless there is a high risk of life-threatening bleeding or other contraindications. | I | B |
| Clopidogrel (300-mg loading dose, 75-mg daily dose) is recommended for patients who cannot receive ticagrelor or prasugrel. | I | A |
| A 600-mg loading dose of clopidogrel (or a supplementary 300-mg dose at PCI following an initial 300-mg loading dose) is recommended for patients scheduled for an invasive strategy when ticagrelor or prasugrel is not an option. | I | B |
| A higher maintenance dose of clopidogrel 150 mg daily should be considered for the first 7 days in patients managed with PCI and without increased risk of bleeding. | IIa | B |
| Increasing the maintenance dose of clopidogrel based on platelet function testing is not advised as routine, but may be considered in selected cases. | IIb | B |
| Genotyping and/or platelet function testing may be considered in selected cases when clopidogrel is used. | IIb | B |
| In patients pre-treated with P2Y12 inhibitors who need to undergo non-emergent major surgery (including CABG), postponing surgery at least for 5 days after cessation of ticagrelor or clopidogrel, and 7 days for prasugrel, if clinically feasible and unless the patient is at high risk of ischaemic events should be considered. | IIa | C |
| Ticagrelor or clopidogrel should be considered to be (re-) started after CABG surgery as soon as considered safe. | IIa | B |
| The combination of aspirin with an NSAID (selective COX-2 inhibitors and non-selective NSAID) is not recommended. | III | C |
COX = cyclo-oxygenase;
CABG = coronary artery bypass graft;
DAPT = dual (oral) antiplatelet therapy;
NSAID = non-steroidal anti-inflammatory drug;
PCI = percutaneous coronary intervention.
| Recommendations for GP IIb/IIIa receptor inhibitors | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| The choice of combination of oral antiplatelet agents, a GP IIb/IIIa receptor inhibitor, and anticoagulants should be made in relation to the risk of ischaemic and bleeding events. | I | C |
| Among patients who are already treated with DAPT, the addition of a GP IIb/IIIa receptor inhibitor for high-risk PCI (elevated troponin, visible thrombus) is recommended if the risk of bleeding is low. | I | B |
| Eptifibatide or tirofiban added to aspirin should be considered prior to angiography in high-risk patients not preloaded with P2Y12 inhibitors. | IIa | C |
| In high-risk patients eptifibatide or tirofiban may be considered prior to early angiography in addition to DAPT, if there is ongoing ischaemia and the risk of bleeding is low. | IIb | C |
| GP IIb/IIIa receptor inhibitors are not recommended routinely before angiography in an invasive treatment strategy. | III | A |
| GP IIb/IIIa receptor inhibitors are not recommended for patients on DAPT who are treated conservatively. | III | A |
GP = glycoprotein;
DAPT = dual (oral) antiplatelet therapy;
LMWH = low-molecular-weight heparin;
PCI = percutaneous coronary intervention;
UFH = unfractionated heparin.
Anticoagulants are used in the treatment of NSTE-ACS to inhibit thrombin generation and/or activity (Figure 4), thereby reducing thrombus-related events. There is evidence that anticoagulation is effective in addition to platelet inhibition and that the combination of the two is more effective than either treatment alone. Several anticoagulants, which act at different levels of the coagulation cascade, have been investigated or are under investigation in NSTE-ACS:
Indirect inhibitors of coagulation (need antithrombin for their full action)
Direct inhibitors of coagulation
| Recommendations for anticoagulants | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Anticoagulation is recommended for all patients in addition to antiplatelet therapy. | I | A |
| The anticoagulation should be selected according to both ischaemic and bleeding risks, and according to the efficacy-safety profile of the chosen agent. | I | C |
| Fondaparinux (2.5 mg subcutaneously daily) is recommended as having the most favourable efficacy-safety profile with respect to anticoagulation. | I | A |
| If the initial anticoagulant is fondaparinux, a single bolus of UFH (85 IU/kg adapted to ACT, or 60 IU in the case of concomitant use of GP IIb/IIIa receptor inhibitors) should be added at the time of PCI. | I | B |
| Enoxaparin (1 mg/kg twice daily) is recommended when fondaparinux is not available. | I | B |
| If fondaparinux or enoxaparin are not available, UFH with a target aPTT of 50-70 s or other LMWHs at the specific recommended doses are indicated. | I | C |
| Bivalirudin plus provisional GP IIb/IIIa receptor inhibitors are recommended as an alternative to UFH plus GP IIb/IIIa receptor inhibitors in patients with an intended urgent or early invasive strategy, particularly in patients with a high risk of bleeding. | I | B |
| In a purely conservative strategy, anticoagulation should be maintained up to hospital discharge. | I | A |
| Discontinuation of anticoagulation should be considered after an invasive procedure unless otherwise indicated. | IIa | C |
| Crossover of heparins (UFH and LMWH) is not recommended. | III | B |
GP = glycoprotein;
DAPT = dual (oral) antiplatelet therapy;
ACT = activated clotting time;
aPTT = activated partial thromboplastin time;
GP = glycoprotein;
LMWH = low-molecular-weight heparin;
PCI = percutaneous coronary intervention;
UFH = unfractionated heparin.
5.4 Coronary revascularization
Revascularization for NSTE-ACS relieves symptoms, shortens hospital stay, and improves prognosis. The indications and timing for myocardial revascularization and choice of preferred approach (PCI or CABG) depend on many factors including the patient's condition, the presence of risk features, co-morbidities, and the extent and severity of the lesions as identified by coronary angiography.
| Table 6: Criteria for high risk with indication for invasive management |
|---|
| See Notes |
| Primary |
| · Relevant rise or fall in troponin
rise/fall of troponin relevant according to precision of assay (see 3.2). · Dynamic ST- or T-wave changes (symptomatic or silent) |
| Secondary |
| · Diabetes mellitus
· Renal insufficiency (eGFR <60 mL/min/1.73 m2) · Reduced LV function (ejection fraction <40%) · Early post infarction angina · Recent PCI · Prior CABG · Intermediate to high GRACE risk score (Table 3) |
CABG = coronary artery bypass graft;
eGFR=estimated glomerular filtration rate;
GRACE = Global Registry of Acute Coronary Events;
LV = left ventricular;
PCI = percutaneous coronary intervention.
| Recommendations for invasive evaluation and revascularization | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
|
An invasive strategy (within 72 h after first presentation) is indicated in patients with:
· at least one high-risk criterion (Table 6); · recurrent symptoms. |
I | A |
| Urgent coronary angiography (<2 h) is recommended in patients at very high ischaemic risk (refractory angina, with associated heart failure, life-threatening ventricular arrhythmias, or haemodynamic instability). | I | C |
| An early invasive strategy (<24 h) is recommended in patients with a GRACE score >140 or with at least one primary high-risk criterion. | I | A |
| Non-invasive documentation of inducible ischaemia is recommended in low-risk patients without recurrent symptoms before deciding for invasive evaluation. | I | A |
| The revascularization strategy (ad-hoc culprit lesion PCI/multivessel PCI/CABG) should be based on the clinical status as well as the disease severity, i.e. distribution and angiographic lesion characteristics (e.g. SYNTAX score), according to the local 'Heart Team' protocol. | I | C |
| As there are no safety concerns related to the use of DESs in ACS, DESs are indicated based on an individual basis taking into account baseline characteristics, coronary anatomy, and bleeding risk. | I | A |
| PCI of non-significant lesions is not recommended. | III | C |
| Routine invasive evaluation of low-risk patients is not recommended. | III | A |
ACS = acute coronary syndromes;
BMS = bare-metal stent;
CABG = coronary bypass graft surgery;
DES = drug-eluting stent;
GRACE = Global Registry of Acute Coronary Events;
PCI = percutaneous coronary intervention;
SYNTAX = SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery.
5.5 Special populations and conditions
Management of NSTE-ACS may need to be adapted in many different subsets of patients or conditions as listed below.
| Recommendations for elderly patients | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Because of the frequent atypical presentation, elderly patients (>75 years) should be investigated for NSTE-ACS at low level of suspicion. | I | C |
| Treatment decisions in the elderly (>75 years) should be made in the context of estimated life expectancy, co-morbidities, quality of life, and patient wishes and preferences. | I | C |
| Choice and dosage of antithrombotic drugs should be tailored in elderly patients to prevent the occurrence of adverse effects. | I | C |
| Elderly patients should be considered for an early invasive strategy with the option of possible revascularization, after careful weighting up of the risks and benefits. | IIa | B |
NSTE-ACS = non-ST-elevation acute coronary syndrome.
| Recommendations for diabetic patients | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| All patients with NSTE-ACS should be screened for diabetes. Blood glucose levels should be monitored frequently in patients with known diabetes or admission hyperglycaemia. | I | C |
| Treatment of elevated blood glucose should avoid both excessive hyperglycaemia [10-11 mmol/L (>180-200 mg/dL)] and hypoglycaemia [<5 mmol/L (<90 mg/dL)]. | I | B |
| Antithrombotic treatment is indicated as in non-diabetic patients. | I | C |
| Renal function should be closely monitored following contrast exposure. | I | C |
| An early invasive strategy is recommended. | I | A |
| DESs are recommended to reduce rates of repeat revascularization. | I | A |
| CABG surgery should be favoured over PCI in diabetic patients with main stem lesions and/or advanced multivessel disease. | I | B |
CABG = coronary artery bypass graft;
DES = drug-eluting stent;
NSTE-ACS = non-ST-elevation acute coronary syndrome.
| Recommendations for patients with heart failure | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| β-Blockers and ACE-inhibitors/ARBs appropriately titrated are indicated in patients with NSTE-ACS and LV dysfunction with or without signs of heart failure. | I | A |
| Aldosterone inhibitors, preferably eplerenone, are indicated in patients with NSTE-ACS, LV dysfunction, and heart failure. | I | A |
| Patients with NSTE-ACS and LV dysfunction or heart failure are recommended to undergo coronary revascularization, if amenable to it. | I | A |
| Patients with NSTE-ACS and severe LV dysfunction should be considered after 1 month for device therapy (CRT and/or implantable cardioverter defibrillator) in addition to optimal medical therapy whenever indicated. | IIa | B |
ACE =angiotensin-converting enzyme;
ARB = angiotensin receptor blockers;
CRT = cardiac resynchronization therapy;
LV = left ventricular;
NSTE-ACS = non-ST-elevation acute coronary syndrome.
| Recommendations for gender | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Both genders should be evaluated and treated in the same way. | I | B |
NSTE-ACS = non-ST-elevation acute coronary syndrome.
| Recommendations for patients with CKD | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Kidney function should be assessed by CrCl or eGFR in patients with NSTE-ACS, with special attention to elderly people, women, and patients with low body weight, as near normal serum creatinine levels may be associated with lower than expected CrCl and eGFR levels. | I | C |
| Patients with NSTE-ACS and CKD should receive the same first-line antithrombotic treatment as patients devoid of CKD, with appropriate dose adjustments according to the severity of renal dysfunction. | I | B |
| Depending on the degree of renal dysfunction, dose adjustment or switch to UFH with fondaparinux, enoxaparin, bivalirudin, as well as dose adjustment with small molecule GP IIb/IIIa receptor inhibitors are indicated. | I | B |
| UFH infusion adjusted to aPTT is recommended when CrCl is <30 mL/min or eGFR is <30 mL/min/1.73 m2 with most anticoagulants (fondaparinux <20 mL/min) (See Table 7). | I | C |
| In patients with NSTE-ACS and CKD considered for invasive strategy, hydration and low- or iso-osmolar contrast medium at low volume (<4 mL/kg) are recommended. | I | B |
| CABG or PCI is recommended in patients with CKD amenable to revascularization after careful assessment of the risk-benefit ratio in relation to the severity of renal dysfunction. | I | B |
aPTT = activated partial thromboplastin time;
CrCl = creatinine clearance;
CABG = coronary artery bypass graft;
CKD = chronic kidney disease;
eGFR = estimated glomerular filtration rate;
NSTE-ACS = non-ST-elevation acute coronary syndrome;
PCI = percutaneous coronary intervention;
UFH = unfractionated heparin.
| Table 7: Recommendations for the use of antithrombotic drugs in CKD | |
|---|---|
| Drug | Recommendations |
| See Notes | |
| Clopidogrel | No information in patients with renal dysfunction. |
| Prasugrel | No dose adjustment necessary, including in patients with end-stage disease. |
| Ticagrelor | No dose reduction required; no information in dialysis patients. |
| Enoxaparin | Dose reduction to 1 mg/kg once daily in the case of severe renal failure (CrCl <30 mL/min). Consider monitoring of anti-Xa activity. |
| Fondaparinux | Contraindicated in severe renal failure (CrCl <20 mL/min). Drug of choice in patients with moderately reduced renal function (CrCl 30-60 mL/min). |
| Bivalirudin | Patients with moderate renal impairment (30-59 mL/min) should receive an infusion of 1.75 mg/kg/h. If the creatinine clearance is <30 mL/min, reduction of the infusion rate to 1 mg/kg/h should be considered. No reduction in the bolus dose is needed. If a patient is on haemodialysis, the infusion rate should be reduced to 0.25 mg/kg/h. |
| Abciximab | No specific recommendations for the use of abciximab, or for dose adjustment in the case of renal failure. Careful evaluation of haemorrhagic risk is needed before using the drug in the case of renal failure. |
| Eptifibatide | The infusion dose should be reduced to 1 μg/kg/min in patients with CrCl <50 mL/min. The dose of the bolus remains unchanged at 180 μg/kg. Eptifibatide is contraindicated in patients with CrCl <30 mL/min. |
| Tirofiban | Dose adaptation is required in patients with renal failure; 50% of the bolus dose and infusion if CrCl is <30 mL/min. |
Recommendations for the use of drugs listed in this table may vary depending on the exact labelling of each drug in the country where it is used.
CrCl = creatinine clearance.
| Recommendations for anaemia | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
Level of Evidence = Level |
||
| Low baseline haemoglobin is an independent marker of the risk of ischaemic and bleeding events and therefore haemoglobin measurement is recommended for risk stratification. | I | B |
| Blood transfusion is only recommended in the case of compromised haemodynamic status or haematocrit <25% or haemoglobin level <7 g/dL. | I | B |
| Recommendations for bleeding complications | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
Level of Evidence = Level |
||
| Assessment of the individual bleeding risk is recommended on the basis of baseline characteristics (by use of risk scores), type, and duration of pharmacotherapy. | I | C |
| Drugs or combinations of drugs and non-pharmacological procedures (vascular access) known to carry a reduced risk of bleeding are indicated in patients at high risk of bleeding. | I | B |
| Interruption and/or neutralization of both anticoagulant and antiplatelet therapies is indicated in case of major bleeding, unless it can be adequately controlled by specific haemostatic measures. | I | C |
| Co-medication of proton pump inhibitors and antithrombotic agents is recommended in patients at increased risk of gastrointestinal haemorrhage. | I | B |
| Minor bleeding should preferably be managed without interruption of active treatments. | I | C |
| Interruption of antiplatelet drugs and neutralization of their activity with platelet transfusion is recommended, depending on the drugs under consideration and the severity of bleeding. | I | C |
| Blood transfusion may have deleterious effects on outcome, and is therefore indicated only after individual assessment, but withheld in haemodynamically stable patients with haematocrit >25% or haemoglobin level >7 g/dL. | I | B |
| Erythropoietin is not indicated as a treatment for anaemia or blood loss. | III | A |
| Recommendations for thrombocytopenia | ||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| Immediate interruption of GP IIb/IIIa receptor inhibitors and/or heparin (UFH or LMWH) is indicated in the case of significant thrombocytopenia (<100 000/μL or >50% drop in platelet count) occurring during treatment. | I | C |
| Platelet transfusion with or without fibrinogen supplementation with fresh frozen plasma or cryoprecipitate in the case of bleeding is indicated in the case of severe thrombocytopenia (<10 000/μL) induced by GP IIb/IIIa receptor inhibitors. | I | C |
| Interruption of heparin (UFH or LMWH) is indicated in the case of documented or suspected HIT, to be replaced by a DTI in the case of thrombotic complications. | I | C |
| Anticoagulants with a low risk of HIT or devoid of risk of HIT (such as fondaparinux or bivalirudin) or brief administration of heparin (UFH or LMWH) - in cases where these compounds are chosen as anticoagulant - is recommended to prevent the occurrence of HIT. | I | C |
DTI = direct thrombin inhibitor;
GP = glycoprotein;
HIT = heparin-induced thrombocytopenia;
LMWH = low-molecular-weight heparin;
UFH = unfractionated heparin.
Secondary prevention is of paramount importance since ischaemic events continue to accrue at a high rate after the acute phase. All measures and treatments with proven efficacy in secondary prevention should be implemented. Enrolment in a cardiac rehabilitation/ secondary prevention programme can enhance patient compliance with the medical regimen and is particularly advised to those with multiple modifiable risk factors and to moderate- to high-risk patients in whom supervised guidance is warranted.
| Recommendations for drugs in secondary prevention
(see separate recommendations for antithrombotic treatment) |
||
|---|---|---|
| Recommendations | Class | Level |
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
||
| β-blockers are recommended in all patients with reduced LV systolic function (LVEF ≤40%). | I | A |
| ACE inhibitors are indicated within 24 h in all patients with LVEF ≤40% and in patients with heart failure, diabetes, hypertension, or CKD, unless contraindicated. | I | A |
| ACE inhibitors are recommended for all other patients to prevent recurrence of ischaemic events, with preference given to agents and doses of proven efficacy. | I | B |
| ARBs are recommended for patients who are intolerant to ACE inhibitors, with preference given to agents and doses of proven efficacy. | I | B |
| Aldosterone blockade with eplerenone is indicated in patients after MI who are already being treated with ACE inhibitors and β-Blockers and who have an LVEF ≤35% and either diabetes or heart failure, without significant renal dysfunction [serum creatinine >221 μmol/L (>2.5 mg/dL) for men and >177 μmol/L (>2.0 mg/dL) for women] or hyperkalaemia. | I | A |
| Statin therapy with target LDL-C levels <1.8 mmol/L (<70 mg/dL) initiated early after admission is recommended. | I | B |
ACE = angiotensin-converting enzyme;
ARB = angiotensin receptor blocker;
CKD = chronic kidney disease;
LDL-C = low-density lipoprotein cholesterol;
LV = left ventricular;
LVEF = left ventricular ejection fraction;
MI = myocardial infarction.
Development of regional and/or national programmes to measure performance indicators systematically and provide feedback to individual hospitals is recommended.
The benefit/risk of the recommended treatments in terms of NNT and numbers needed to harm can be assessed as depicted in Figure 5.
| Table 8: Useful determinants of performance in NSTEMI patients are: |
|---|
| See Notes |
| · Use of aspirin |
| · Use of clopidogrel/prasugrel/ticagrelor |
| · Use of UFH/enoxaparin/fondaparinux/bivalirudin |
| · β-blocker at discharge in patients with LV dysfunction |
| · Use of statins |
| · Use of ACE-inhibitor or ARB |
| · Use of early invasive procedures in intermediate- to high-risk patients |
| · Smoking cessation advice/counseling |
| · Enrolment in a secondary prevention/ cardiac rehabilitation programme |
ACE = angiotensin-converting enzyme;
ARB = angiotensin receptor blocker;
LV = left ventricular;
UFH = unfractionated heparin.
This section summarizes the diagnostic and therapeutic steps allowing standardization of the clinical routine work-up and thereby improving quality of care. However, specific findings in individual patients may result in appropriate deviations from the proposed strategy since NSTE-ACS encompasses a heterogeneous spectrum of patients with different levels of risk in terms of death, MI, or recurrence of MI. For every patient, the physician must make an individual decision, taking into account the patient's history (co-morbid illnesses, age, etc.), his/her clinical condition, findings during the initial assessment on first contact, and the available pharmacological and non-pharmacological treatment options.
Step one: Initial evaluation
Chest pain or discomfort suggestive of ACS or other symptoms as described in Section 3.1 will lead to the patient seeking medical attention or hospitalization. A patient with suspected NSTE-ACS must be evaluated in a hospital and seen immediately by a qualified physician. Specialized chest pain units or coronary care units provide the best and most expeditious care.
The initial step is to assign the patient without delay to a working diagnosis on which the treatment strategy will be based. The assessment criteria are the following:
On the basis of these findings, which should be available within 10 min of first medical contact, the patient can be assigned to one of the three major working diagnoses:
The treatment of patients with STEMI is covered in the respective guidelines. The assignment to the category 'unlikely' must be done with caution and only when another explanation is obvious (e.g. thorax trauma). The initial treatment measures are summarized in Table 9.
Blood is drawn on arrival of the patient in hospital and the results should be available within 60 min to be used in the second step. Initial blood tests must at least include: troponin T or I, creatinine, haemoglobin, blood glucose, and blood cell count, in addition to standard biochemistry tests.
| Table 9: Initial therapeutic measures | |
|---|---|
| Oxygen | Insufflation (4-8 L/min) if oxygen saturation is <90% |
| Nitrates | Sublingual or intravenous (caution if systolic blood pressure is <90 mmHg) |
| Morphine | 3-5 mg intravenous or subcutaneously, if severe pain |
Assignment of the patient to the NSTE-ACS category will lead on to step two - diagnosis validation and risk assessment.
Step two: Diagnosis validation and risk assessment
After the patient is assigned to the group NSTE-ACS, i.v. and oral antithrombotic treatments will be started according to Table 10. Further management of the patient will be based on additional information/data:
During step two, other diagnoses may be confirmed or excluded, such as pulmonary embolism and aortic aneurysm.
Treatment of the individual patient is tailored according to their risk for subsequent events, which should be assessed early at the initial presentation as well as repeatedly thereafter in the light of continuing or repetitive symptoms and additional information from clinical chemistry or imaging modalities.
Risk assessment is an important component of the decision-making process and is subject to constant re-evaluation. It encompasses assessment of ischaemic and bleeding risk. The risk factors for bleeding and ischaemic events overlap considerably, with the result that patients at high risk of ischaemic events are also at high risk of bleeding.
Therefore, the choice of pharmacological environment (dual or triple antiplatelet therapy, anticoagulants) is important, as is the dosage of the drugs and the access site in case of angiography. Particular attention has to be paid to renal dysfunction, shown to be particularly frequent in elderly patients and diabetic patients. The pharmacological options are summarized in Table 10.
| Table 10: Checklist of treatments when an ACS diagnosis appears likely | |
|---|---|
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
|
| Aspirin | Initial dose of 150-300 mg non-enteric formulation followed by 75-100 mg/day (i.v. administration is acceptable) |
| P2Y12 inhibitor | Loading dose of ticagrelor or clopidogrel |
| Anticoagulation | Choice between different options depends on strategy:
· Fondaparinux 2.5 mg/daily subcutaneously · Enoxaparin 1 mg/kg twice daily subcutaneously · UFH i.v. bolus 60-70 IU/kg (maximum 5000 IU) followed by infusion of 12-15 IU/kg/h (maximum 1000 IU/h) titrated to aPTT 1.5-2.5 x control · Bivalirudin is indicated only in patients with a planned invasive strategy |
| Oral β-Blocker | If tachycardic or hypertensive without signs of heart failure |
aPTT = activated partial thromboplastin time;
IU = international units;
i.v. = intravenous;
UFH = unfractionated heparin.
Step three: invasive strategy
Cardiac catheterization followed by revascularization has been shown to prevent recurrent ischaemia and/or improve short- and long-term outcomes. Several risk factors (troponin elevation, diabetes, ST-depression, renal insufficiency, etc.) have been identified to predict the long-term benefit of an invasive strategy. Depending on the acuteness of risk, the timing of angiography can be tailored, according to four categories (Figure 6):
The optimal timing depends on the risk profile of the individual patient and can be assessed by several variables.
Urgent invasive strategy (<120 min after first medical contact) should be undertaken for very high-risk patients. These patients are characterized by:
A GP IIb/IIIa receptor inhibitor (eptifibatide or tirofiban) may be considered in patients with such features in order to bridge the time to catheterization. A checklist of antithrombotic treatments prior to PCI is given in Table 11.
Early invasive strategy (<24 h after first medical contact)
Most patients initially respond to the antianginal treatment, but are at increased risk and need angiography followed by revascularization. High-risk patients as identified by a GRACE risk score >140 and/or presence of at least one primary high-risk criterion (Table 6) should undergo invasive evaluation within 24 h.
Invasive strategy (<72 h after first medical contact)
In patients with less-acute risk, according to Table 6, and without recurrence of symptoms, angiography may be performed within a time window of 72 h. Thus, such patients should undergo elective invasive evaluation at the first opportunity depending on the local circumstances.
Conservative strategy (no or elective angiography)
Patients that fulfil all of the following criteria may be regarded as low risk and should not routinely be submitted to early invasive evaluation:
Low risk as assessed by a risk score (see Section 4.4) should support the decision-making process for a conservative strategy. The further management of these patients is according to the evaluation of stable CAD. Before discharge from hospital, a stress test for inducible ischaemia is useful for treatment planning and required before elective angiography.
| Table 11: Checklist of antithrombotic treatments prior to PCI | |
|---|---|
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
|
| Aspirin | Confirm loading dose prior to PCI |
| P2Y12 inhibitor | Confirm loading dose of ticagrelor or clopidogrel prior to PCI. If P2Y12 naïve, consider prasugrel (if <75 years age, >60 kg, no prior stroke or TIA) |
| Anticoagulation |
· Fondaparinux pre-treated: add UFH for PCI
· Enoxaparin pre-treated: add if indicated · UFH pretreated: titrate to ACT >250 s, or switch to bivalirudin (0.1 mg/kg bolus followed by 0.25 mg/kg/h) |
| GP IIb/IIIa receptor inhibitor | · Consider tirofiban or eptifibatide in patients with high-risk anatomy or troponin elevation
· Abciximab only prior to PCI in high-risk patients |
ACT = activated clotting time;
PCI = percutaneous coronary intervention;
TIA = transient ischaemic attack;
UFH = unfractionated heparin
Step four: revascularization modality
If the angiogram shows atheromatous burden but no critical coronary lesions, patients will be referred for medical therapy. The diagnosis of NSTE-ACS may be reconsidered and particular attention paid to other possible reasons for symptoms at presentation, before the patient is discharged. However, the absence of critical coronary lesions does not rule out the diagnosis if the clinical presentation was suggestive of ischaemic chest pain and if biomarkers were positive. In this situation, patients should receive treatment according to NSTE-ACS.
Recommendations for the choice of a revascularization modality in NSTE-ACS are similar to those for elective revascularization procedures. In patients with single-vessel disease, PCI with stenting of the culprit lesion is the first choice. In patients with multivessel disease, the decision for PCI or CABG must be made individually, according to institutional protocols designed by the 'Heart Team'. A sequential approach, consisting of treating the culprit lesion with PCI followed by elective CABG with proof of ischaemia and/or functional assessment (FFR) of the non-culprit lesions, may be advantageous in some patients.
The anticoagulant should not be changed during PCI. In patients pretreated with fondaparinux, UFH must be added before PCI. A GP IIb/IIIa inhibitor should be considered if troponins are elevated or on angiographic presence of thrombus. If CABG is planned, P2Y12 inhibitors should be stopped and surgery deferred only if the clinical condition and the angiographic findings permit.
If angiography shows no options for revascularization, owing to the extent of the lesions and/or poor distal run-off, freedom from angina at rest should be achieved by intensified medical therapy, and secondary preventive measures should be instituted.
Step five: Hospital discharge and post-discharge
Although in NSTE-ACS most adverse events occur in the early phase, the risk for MI or death remains elevated over several months. Patients treated with early revascularization are at low (2.5%) risk for developing life-threatening arrhythmias, with 80% occurring during the first 12 h after onset of symptoms. Accordingly, routine monitoring of the patients beyond 24-48 h is not warranted. Patients with NSTE-ACS should be hospitalized for at least 24 h after successful stenting of the culprit lesion.
Intense risk-factor modification and lifestyle change are warranted in all patients following the diagnosis of NSTE-ACS. Enrolment in a cardiac rehabilitation program after discharge can enhance patient adherence to the medical regimen and may be supportive in risk factor modification. A checklist of measures necessary at discharge from hospital is given in Table 12.
| Table 12: Measures checked at discharge | |
|---|---|
|
Class of Recommendation = Class
See Notes Level of Evidence = Level |
|
| Aspirin | Continue life long |
| P2Y12 inhibitor | Continue for 12 months (unless at high risk of bleeding) |
| β-blocker | If LV function depressed |
| ACE inhibitor/ARB | If LV function depressed Consider for patients devoid of depressed LV function |
| Aldosterone antagonist / eplerenone | If depressed LV function (LVEF ≤35%) and either diabetes or heart failure, without significant renal dysfunction |
| Statin | Titrate to achieve target LDL-C levels <1.8 mmol/L (<70 mg/dL) |
| Lifestyle | Risk-factor counselling, referral to cardiac rehabilitation / secondary prevention programme |
ACE = angiotensin-converting enzyme;
ARB = angiotensin receptor blocker;
LDL-C = low-density lipoprotein cholesterol;
LV = left ventricular;
LVEF = left ventricular ejection fraction.
Useful internet links:
References for further reading:
© 2011 The European Society of Cardiology
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