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Acute Coronary Syndromes Clinical Practice Guidelines (ESC, 2020)

In late August 2020, the European Society of Cardiology (ESC) released their updated guidelines for the diagnosis and management of non ST-elevation (NSTE) acute coronary syndrome (ACS).^{[84, 85]}The updates place increased reliance on high-sensitivity cardiac troponin testing (hs-cTn) for diagnosis, embrace coronary computed tomography (CT) imaging to rule out lower-risk patients, as well as highlight the need for personalized antiplatelet regimens, systems of care, and quality improvement. Key messages are below.

Diagnosis

Chest discomfort without persistent ST-segment elevation (NSTE-ACS) is the main symptom that initiates the diagnostic and therapeutic chain. The myocardial pathology consists of cardiomyocyte necrosis, measured by troponin release, or, less often, myocardial ischemia without cell damage (unstable angina). Those with unstable angina have a much lower death risk and benefit less from an aggressive pharmacologic and invasive approach.

Troponin assays and other biomarkers

The ESC recommends Hs-cTn assays over less sensitive assays (higher diagnostic accuracy, same low cost). Note that many cardiac conditions other than myocardial infarction (MI) also result in cardiomyocyte injury and can raise cTn levels.

Biomarkers such as creatine kinase myocardial band (CK-MB) and copeptin may be clinically relevant in specific circumstances when used with non hs-cTn T or I (T/I). There is a more rapid post-MI reduction of CK-MB, and it may have an added value for detecting early reinfarction. Routine use of copeptin is recommended as an additional biomarker for the early exclusion of MI in the infrequent setting of unavailable hs-cTn assays.

Rapid “rule-in” and “rule-out” algorithms

Use of hs-cTn assays (higher sensitivity, diagnostic accuracy) can shorten the time interval to the second cTn assessment for detecting MI at presentation. Recommendations include using the 0 h/1 h algorithm (best option, blood draw at 0 h and 1 h) or the 0 h/2 h algorithm (second-best option, blood draw at 0 h and 2 h). Use of the 0 h/1 h and 0 h/2 h algorithms with clinical and electrocardiographic (ECG) findings aid in identifying appropriate candidates for early discharge and outpatient management.

Hs-cTn confounders

Four clinical variables affect hs-cTn levels besides the presence/absence of MI, as follows:

Age: Up to 300% differences in concentration between healthy very young versus “healthy” very old individuals
Renal dysfunction: Up to 300% differences in concentration between otherwise healthy patients with very high versus very low estimated glomerular filtration rate (eGFR)
Chest pain onset: Over 300%
Sex: About 40%

Ischemic and bleeding risk assessments

Initial cTn levels add prognostic information about short- and long-term mortality to clinical and ECG variables (higher hs-cTn levels raise mortality risk). Measure serum creatinine and eGFR in all patients with NSTE-ACS; they are prognostic factors and key elements of the Global Registry of Acute Coronary Events (GRACE) risk score (superior assessment to subjective physician assessment for the occurrence of death or MI). Natriuretic peptides may add incremental prognostic information and may aid in risk stratification.

Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a pragmatic approach for evaluating bleeding risk (includes the most recent trials of HBR patients previously excluded from clinical trials of dual antiplatelet therapy [DAPT] duration or intensity). The PRECISE-DAPT (PRE dicting bleeding C omplications I n patients undergoing S tent implantation and subsEquent DAPT) score may be used to guide and inform decision making on DAPT duration with a modest predictive value for major bleeding. Their value in improving patient outcomes remains unclear.

Noninvasive imaging

After MI has been excluded, elective noninvasive/invasive imaging may still be indicated based on clinical assessment. Coronary CT angiography (CCTA) may be an option in those with a low-to-modest clinical likelihood of unstable angina as a normal scan excludes coronary artery disease (CAD): It has a high negative predictive value (NPV) to rule out ACS (by excluding CAD) and a positive outcome in patients presenting to the emergency department with a low-to-intermediate pretest probability for ACS and a normal CCTA. Upfront imaging with CCTA also reduces the need for invasive coronary angiography (ICA) in high-risk patients. Other imaging options based on risk evaluation include stress imaging by cardiac magnetic resonance imaging (CMRI), stress echocardiography, or nuclear imaging.

Risk Stratification for an Invasive Approach

The ESC recommends an early routine invasive approach within 24 hours of admission for NSTEMI (based on hs-cTn levels, GRACE risk score >140, and dynamic new/presumably new ST-segment changes) to improve major adverse cardiac events and possibly early survival. Highly unstable patients require immediate invasive angiography based on hemodynamic status, arrhythmias, acute heart failure, or persistent chest pain. For all other clinical presentations, a selective invasive approach may be performed based on noninvasive testing or clinical risk assessment.

Revascularization Strategies

The main technical aspects of percutaneous coronary intervention (PCI) in NSTE-ACS patients do not differ from the invasive assessment and revascularization strategies for other manifestations of CAD. Radial access is the recommended and preferred approach in NSTE-ACS patients undergoing invasive assessment with or without PCI. As NSTE-ACS commonly involves multivessel disease, base the determination of revascularization timing and completeness on the functional relevance of all stenoses, patient age and comorbidities, general clinical condition, and left ventricular function.

MI With Nonobstructive Coronary Arteries (MINOCA)

MINOCA comprises a heterogeneous group of underlying causes potentially involving both coronary and noncoronary pathologic conditions, with the latter including cardiac and extra-cardiac disorders. By consensus, myocarditis and Takotsubo syndrome are excluded. CMRI, a key diagnostic tool, identifies the underlying cause in over 85% of patients and the subsequent appropriate treatment.

Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection is a nonatherosclerotic, nontraumatic, or iatrogenic separation of the coronary arterial tunics due to vasa vasorum hemorrhage or intimal tear. It comprises up to 4% of all ACS but has a higher reported incidence (22-35% of ACS) in women younger than age 60 years. Intracoronary imaging is very useful for the diagnosis and treatment strategy. Medical treatment remains to be established.

Pretreatment With P2Y12 Receptor Inhibitors

Due to a lack of established benefit, the ESC does not recommend routine pretreatment with a P2Y12 receptor inhibitor in NSTE-ACS patients with unknown coronary anatomy and a planned early invasive management. However, it may be considered in selected cases and based on the patient’s bleeding risk.

Posttreatment APT

Barring contraindications, DAPT consisting of a 12-month regimen of a potent P2Y12 receptor inhibitor plus aspirin is generally recommended, regardless of the stent type. DAPT duration can be shortened (< 12 months), extended (>12 months), or modified by switching DAPT or de-escalation, based on individual clinical judgment according to the patient’s ischemic and bleeding risks, the occurrence of adverse events, comorbidities, co-medications, and the availability of the respective drugs.

Triple Antithrombotic Therapy (TAT)

In at least 6-8% of patients undergoing PCI, long-term oral anticoagulation is indicated and should be continued. For eligible patients, non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists (VKAs). The ESC recommends dual antithrombotic therapy (DAT) with a NOAC for stroke prevention and single antiplatelet therapy (SAPT) (clopidogrel is preferred) as the default strategy up to 12 months after a short period up to 1 week of TAT (NOAC + DAPT). TAT may be prolonged up to 1 month when the ischemic risk outweighs the bleeding risk.

2014 AHA/ACC and 2015 ESC Guidelines for the Management NSTE-ACS

Guidelines for the management of non–ST-elevation acute coronary syndromes (NSTE-ACS) have been issued by the American Heart Association/American College of Cardiology (AHA/ACC) in 2014 and the European Society of Cardiology (ESC) in 2015. A summary of these guidelines are below.

In 2014, the AHA/ACC published a full revision of their 2007 guidelines which included the following key changes^[42]:

Because unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI) are on a pathophysiologic continuum and are often indistinguishable, they are considered together in the 2014 guidelines
To more clearly convey this physiology-based patient-management approach, the guideline has replaced the term "initial conservative management" with "ischemia-guided strategy"
Cardiac troponin assays may improve the diagnosis of myocardial necrosis
High-intensity statins should be used in patients with overt cardiovascular disease
Risk stratification tools in these patients include the Thrombolysis in Myocardial Infarction (TIMI) risk score and the Global Registry of Acute Coronary Events (GRACE) risk score

In 2015, the ESC released its guidelines which define unstable angina as "myocardial ischemia at rest or minimal exertion in the absence of cardiomyocyte necrosis."^[86]

Evaluation

The 2014 AHA/ACC revised guidelines include the following recommendations for evaluation of patients with suspected ACS^[42]:

Class I

Patients with suspected ACS should be risk stratified based on the likelihood of ACS and adverse outcome(s) to decide on the need for hospitalization and assist in the selection of treatment options. (Level of evidence: B)

Patients with suspected ACS and high-risk features such as continuing chest pain, severe dyspnea, syncope/presyncope, or palpitations should be referred immediately to the emergency department (ED) and transported by emergency medical services when available. (Level of evidence: C)

In patients with chest pain or other symptoms suggestive of ACS, a 12-lead electrocardiogram (ECG) should be performed and evaluated for ischemic changes within 10 minutes of the patient’s arrival at an emergency facility. (Level of evidence: C)

Serial ECGs (eg, 15- to 30-minute intervals during the first hour) should be performed to detect ischemic changes if the initial ECG is not diagnostic but the patient remains symptomatic. (Level of evidence: C)

Serial cardiac troponin I or T levels (when a contemporary assay is used) should be obtained at presentation and 3 to 6 hours after symptom onset in all patients who present with symptoms consistent with ACS to identify a rising and/or falling pattern of values. If the time of symptom onset is ambiguous, the time of presentation should be considered the time of onset for assessing troponin values. (Level of evidence: A)

Additional troponin levels should be obtained beyond 6 hours after symptom onset in patients with normal troponin levels on serial examination when changes on ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS. (Level of evidence: A)

Class IIa

It is reasonable to give low-risk patients who are referred for outpatient testing daily aspirin, short-acting nitroglycerin, and other medication if appropriate (eg, beta blockers), with instructions about activity level and clinician follow-up. (Level of evidence: C)

Observe patients with symptoms consistent with ACS without objective evidence of myocardial ischemia (nonischemic initial ECG and normal cardiac troponin) in a chest pain unit or telemetry unit with serial ECGs and cardiac troponin levels at 3- to 6-hour intervals. (Level of evidence: B)

For patients with possible ACS who have normal serial ECGs and cardiac troponin levels, it is reasonable to obtain a treadmill ECG (level of evidence: A), stress myocardial perfusion imaging, or stress echocardiography before discharge or within 72 hours after discharge (level of evidence: B).

In patients with possible ACS and a normal ECG, normal cardiac troponin levels, and no history of coronary artery disease (CAD), it is reasonable to initially perform (without serial ECGs and troponin levels) coronary computed tomography angiography to assess coronary artery anatomy (level of evidence: A) or rest myocardial perfusion imaging with a technetium-99m radiopharmaceutical to exclude myocardial ischemia (level of evidence: B).

The 2015 ESC guidelines are in general agreement with the 2014 AHA/ACC. Additional Class I recommendations are summarized below^[86]

Base the diagnosis and initial short-term ischemic and bleeding risk stratification on a combination of clinical history, symptoms, vital signs, other physical findings, ECG, and laboratory results. (Level of evidence: A)

Measure cardiac troponin levels with sensitive or high-sensitivity assays, and obtain the results within 60 minutes. (Level of evidence: A)

A rapid rule-out protocol at 0 h and 3 h if high-sensitivity cardiac troponin tests are available. (Level of evidence: B)

A rapid rule-out and rule-in protocol at 0 h and 1 h if a high-sensitivity cardiac troponin test with a validated 0 h/1 h algorithm is available. Additional testing after 3 to 6 hours is indicated if the first two troponin measurements are not conclusive and the clinical condition is still suggestive of ACS.(Level of evidence: B)

Continuous rhythm monitoring should be performed until the diagnosis of NSTEMI is established or ruled out. (Level of evidence: C)

In the absence of signs or symptoms of ongoing ischemia, rhythm monitoring in unstable angina may be considered in selected patients (eg, suspicion of coronary spasm or associated symptoms suggestive of arrhythmic events).

Selection of management strategy

Determination of the preferred management strategy depends on the patient’s clinical characteristics and clinical risk. The AHA/ACC and ESC provide similar recommendations for selection of the preferred management strategy which are summarized in Table 5 below.^{[42, 86]}

Table 5. Recommendations for Selection of Preferred Management Strategy (Open Table in a new window)

Preferred Strategy	Patient Characteristic/Clinical Risk
Immediate Invasive Strategy (< 2 hours)	Refractory angina
	Signs/symptoms of heart failure or new or worsening mitral regurgitation
	Hemodynamic instability or cardiogenic shock
	Recurrent angina/ischemia at rest or with low-level activities despite intensive medical therapy
	Sustained ventricular tachycardia or ventricular fibrillation
Ischemia-Guided Strategy	Low-risk score (eg, TIMI 0 or 1, GRACE < 109)
	Low-risk Tn-negative female
	Patient or physician preference in the absence of high-risk features
Early Invasive Strategy (< 24 hours)	GRACE score >140
	Rise or fall in Tn compatible with myocardial infarction
	New or presumably new ST-segment depression
Delayed Invasive Strategy (24-72 hours)	Diabetes mellitus
	Renal insufficiency (GFR < 60 mL/min/1.73m²)
	Reduced LV systolic function (LVEF < 40%)
	Early postinfarction angina
	PCI within 6 months
	Prior CABG
	GRACE score 109-140; TIMI Score ≥2
ACC/AHA = American College of Cardiology/American Heart Association; CABG = coronary artery bypass grafting; GFR = glomerular filtration rate; GRACE = Global Registry of Acute Coronary Events; LV = left ventricle; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis in Myocardial Infarction Clinical Trial; Tn = troponin.

Initial hospital care

The 2014 AHA/ACC recommendations for initial hospital care are summarized below.^[42]

Oxygen

Administer supplemental oxygen only with oxygen saturation below 90%, respiratory distress, or other high-risk features for hypoxemia. (Class I; level of evidence C)

Nitrates

Administer sublingual nitroglycerin (NTG) every 5 minutes three times for continuing ischemic pain, and then assess need for intravenous (IV) NTG. (Class I; level of evidence: C)

Administer IV NTG for persistent ischemia, heart failure (HF), or hypertension. (Class I; level of evidence: B)

Nitrates are contraindicated with recent use of a phosphodiesterase inhibitor. (Class III; level of evidence: B)

Analgesic therapy

IV morphine sulfate may be reasonable for continued ischemic chest pain despite maximally tolerated anti-ischemic medications. (Class IIb; level of evidence: B)

Nonsteroidal anti-inflammatory agents (NSAIDs) (except aspirin) should not be initiated and should be discontinued because of the increased risk of a major adverse cardiac event associated with their use. (Class III; level of evidence: B)

Beta-adrenergic blockers

Initiate oral beta blockers in the absence of HF, low-output state, risk for cardiogenic shock, or other contraindications to beta blockade. (Class I; level of evidence: A)

Use sustained-release metoprolol succinate, carvedilol, or bisoprolol for beta-blocker therapy with concomitant NSTE-ACS, stabilized HF, and reduced systolic function. (Class I; level of evidence: C)

Re-evaluate to determine subsequent eligibility in patients with initial contraindications to beta blockers. (Class I; level of evidence: C)

It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACS. (Class IIa; level of evidence: C)

IV beta blockers are potentially harmful when risk factors for shock are present. (Class III; level of evidence: B)

Calcium channel blockers (CCBs)

CCBs are recommended for ischemic symptoms when beta blockers are not successful, are contraindicated, or cause unacceptable side effects. (Class I; level of evidence: C)

Long-acting CCBs and nitrates are recommended for patients with coronary artery spasm. (Class I; level of evidence: C)

Administer initial therapy with nondihydropyridine CCBs with recurrent ischemia and contraindications to beta blockers in the absence of LV dysfunction, increased risk for cardiogenic shock, PR interval above 0.24 s, or second- or third-degree atrioventricular block without a cardiac pacemaker. (Class I; level of evidence: B)

Administer oral nondihydropyridine calcium antagonists with recurrent ischemia after use of beta blocker and nitrates in the absence of contraindications. (Class I; level of evidence: C)

Immediate-release nifedipine is contraindicated in the absence of a beta blocker. (Class III; level of evidence: B)

Cholesterol management

Initiate or continue high-intensity statin therapy in patients with no contraindications. (Class I; level of evidence: A)

Obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation. (Class IIa; level of evidence: C)

Angiotensin-converting enzyme (ACE) inhibitors (ACEIs)

Class I

ACEIs should be started and continued indefinitely in all patients with an LVEF) below 0.40 and in those with hypertension, diabetes mellitus, or stable chronic kidney disease (CKD), unless contraindicated. (Level of evidence: A)

Angiotensin receptor blockers are recommended in patients with heart failure or MI with LVEF below 0.40 who are intolerant to ACEIs. (Level of evidence: A)

Aldosterone blockade is recommended in post–MI patients who are without significant renal dysfunction or hyperkalemia who are receiving therapeutic doses of ACEI and beta blocker and have an LVEF below 0.40, diabetes mellitus, or heart failure. (Level of evidence: A)

Antiplatelet therapy

Recommendations for initial antiplatelet/anticoagulation therapy in patients with NSTE-ACS are summarized below.^[42]

Aspirin

Nonenteric-coated, chewable aspirin (162 mg to 325 mg) should be given to all patients without contraindications as soon as possible after presentation, and a maintenance dose of aspirin (81 mg/d to 325 mg/d) should be continued indefinitely. (Class I; level of evidence A)

In patients who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance, a loading dose of clopidogrel followed by a daily maintenance dose should be administered. (Class I; level of evidence B)

Anticoagulation

Anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of the initial treatment strategy. Treatment options (all Class I) include:

Subcutaneous (SC) enoxaparin for duration of hospitalization or until percutaneous coronary intervention (PCI) is performed (Level of evidence: A)
Bivalirudin until diagnostic angiography or PCI is performed in patients with early invasive strategy only (Level of evidence: B)
SC fondaparinux for the duration of hospitalization or until PCI is performed (Level of evidence: B)
IV unfractionated heparin (UFH) for 48 h or until PCI is performed (Level of evidence: B)

IV fibrinolytic treatment is not recommended in patients with NSTE-ACS. (Class III, level of evidence: A)

Dual antiplatelet therapy

In 2016, the ACC/AHA released updated guidelines on the duration of dual antiplatelet therapy (DAPT) in patients with CAD. In this focused update, the term and acronym DAPT is used to specifically to refer to combination antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). Key recommendations for patients with NSTE-ACS treated with DAPT are summarized below.^[87]:

Class I

For all patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended. (Level of evidence: B-R)

After bare metal stent (BMS) or drug-eluting stent (DES) implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months. (Level of evidence: B-R)

For patients who subsequently undergo CABG after coronary stent implantation, P2Y12 inhibitor therapy should be resumed postoperatively so that DAPT continues until the recommended duration of therapy is completed. (Level of evidence: C-EO)

In patients who undergo CABG, P2Y12 inhibitor therapy should be resumed after CABG to complete 12 months of DAPT therapy. (Level of evidence: C-LD)

Class IIa

After coronary stent implantation, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy. (Level of evidence: B-R)

After coronary stent implantation in patients who are not at high risk for bleeding complications and who do not have a history of stroke or transient ischemic attack (TIA), it is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor therapy.(Level of evidence: B-R)

Class IIb

In patients treated with coronary stent implantation who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk, continuation of DAPT (clopidogrel, prasugrel, or ticagrelor) for longer than 12 months may be reasonable. (Level of evidence: A)

After DES implantation, patients who develop a high risk of bleeding, or are at high risk of severe bleeding complication, or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 6 months may be reasonable. (Level of evidence: C-LD)

Class III

Prasugrel should not be administered to patients with a prior history of stroke or TIA. (Level of evidence: B-R)

Hospital discharge and follow-up

The 2014 AHA/ACC guidelines include the following Class 1 recommendations for posthospital care^[42]:

Medications required in the hospital to control ischemia should be continued after hospital discharge in patients with NSTE-ACS who do not undergo coronary revascularization, patients with incomplete or unsuccessful revascularization, and patients with recurrent symptoms after revascularization. Titration of the doses may be required. (Level of evidence: C)

All patients should be given sublingual or spray NTG with verbal and written instructions for its use. (Level of evidence: C)

Before hospital discharge, patients should be informed about symptoms of worsening myocardial ischemia and Ml, and they should be given verbal and written instructions about how and when to seek emergency care for such symptoms. (Level of evidence: C)

For patients who have initial angina lasting more than 1 minute, NTG (1 dose sublingual or spray) if angina does not subside within 3 to 5 minutes; call 9-1-1 immediately to access emergency medical services. (Level of evidence: C)

If the pattern or severity of angina changes, suggesting worsening myocardial ischemia (eg, pain is more frequent or severe or is precipitated by less effort or occurs at rest), patients should contact their clinician without delay to assess the need for additional treatment or testing. (Level of evidence: C)

Before discharge, patients should be educated about modification of cardiovascular risk factors. (Level of evidence: C)

Diabetes

The 2014 AHA/ACC guidelines recommend that treatment in the acute phase of NSTE-ACS and decisions to perform stress testing, angiography, and revascularization should be similar in patients with and without diabetes mellitus. (Level of evidence: A)

The 2015 ESC guidelines offer the following recommendations^[86]:

Class I

Screen all patients for diabetes and monitor blood glucose levels frequently in patients with known diabetes or admission hyperglycemia. (Level of evidence: C)

Administer the same antithrombotic treatment in diabetic and nondiabetic patients. (Level of evidence: C)

An invasive strategy is recommended over noninvasive management. (Level of evidence: A)

Monitor renal function for 2-3 days after coronary angiography or PCI in patients with baseline renal impairment or on metformin. (Level of evidence: C)

In patients undergoing PCI, new-generation DESs are recommended over BMSs. (Level of evidence: A)

In patients with stabilized multivessel CAD and an acceptable surgical risk, CABG is recommended over PCI. (Level of evidence: A)

Class IIa

Glucose-lowering therapy should be considered in ACS patients with blood glucose above 10 mmol/L (>180 mg/dL), with the target adapted to comorbidities, whereas episodes of hypoglycemia should be avoided. (Level of evidence: C)

Less stringent glucose control should be considered in patients with more advanced cardiovascular disease, older age, longer diabetes duration, and more comorbidities. (Level of evidence: C)

Medication

Basra SS, Virani SS, Paniagua D, Kar B, Jneid H. Acute coronary syndromes: unstable angina and non-ST elevation myocardial infarction. Heart Fail Clin. 2016 Jan. 12 (1):31-48. [QxMD MEDLINE Link].
Hedayati T, Yadav N, Khanagavi J. Non-ST-segment acute coronary syndromes. Cardiol Clin. 2018 Feb. 36 (1):37-52. [QxMD MEDLINE Link].
What are the symptoms of heart attack and unstable angina?. eMedicineHealth. May 8, 2013. Available at http://www.emedicinehealth.com/heart_attack_and_unstable_angina-health/page5_em.htm#Symptoms.. Accessed: May 9, 2013.
Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011 Jan 20. 364(3):226-35. [QxMD MEDLINE Link].
Harrap SB, Zammit KS, Wong ZY, et al. Genome-wide linkage analysis of the acute coronary syndrome suggests a locus on chromosome 2. Arterioscler Thromb Vasc Biol. 2002 May 1. 22(5):874-8. [QxMD MEDLINE Link].
Zhao YH, Xu Y, Gu YY, Li Y, Zhang JY, Su X. Functional effect of platelet membrane glycoprotein ia gene polymorphism in the pathogenesis of unstable angina pectoris. J Int Med Res. 2011. 39(2):541-8. [QxMD MEDLINE Link].
Fiotti N, Moretti ME, Bussani R, et al. Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms. Atherosclerosis. 2011 Mar. 215(1):153-9. [QxMD MEDLINE Link].
White AJ, Duffy SJ, Walton AS, et al. Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease. Cardiovasc Res. 2007 Sep 1. 75(4):813-20. [QxMD MEDLINE Link].
Manzoli A, Andreotti F, Varlotta C, et al. Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. Cardiologia. 1999 Sep. 44(9):825-30. [QxMD MEDLINE Link].
Tziakas DN, Chalikias GK, Antonoglou CO, et al. Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease. J Am Coll Cardiol. 2006 Dec 19. 48(12):2471-81. [QxMD MEDLINE Link].
Willerson JT. Systemic and local inflammation in patients with unstable atherosclerotic plaques. Prog Cardiovasc Dis. 2002 May-Jun. 44(6):469-78. [QxMD MEDLINE Link].
Scirica BM, Moliterno DJ, Every NR, et al. Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators. Am J Cardiol. 1999 Nov 15. 84(10):1145-50. [QxMD MEDLINE Link].
Skolnick AH, Alexander KP, Chen AY, et al. Characteristics, management, and outcomes of 5,557 patients age > or =90 years with acute coronary syndromes: results from the CRUSADE Initiative. J Am Coll Cardiol. 2007 May 1. 49(17):1790-7. [QxMD MEDLINE Link].
Hoekstra JW, Pollack CV Jr, Roe MT, et al. Improving the care of patients with non-ST-elevation acute coronary syndromes in the emergency department: the CRUSADE initiative. Acad Emerg Med. 2002 Nov. 9(11):1146-55. [QxMD MEDLINE Link].
Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Lancet. 1999 Feb 6. 353(9151):429-38. [QxMD MEDLINE Link].
Luepker RV. WHO MONICA project: what have we learned and where to go from here?. Public Health Rev. 2012. Accessed: May 8, 2013. 33(2):373-96. [Full Text].
GRACE, Global Registry of Acute Coronary Events. Available at http://www.outcomes-umassmed.org/grace/. Accessed: September 16, 2010.
Puelacher C, Gugala M, Adamson PD, et al. Incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction. Heart. 2019 Apr 24. [QxMD MEDLINE Link].
Cannon CP, McCabe CH, Stone PH, et al. The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia. J Am Coll Cardiol. 1997 Jul. 30(1):133-40. [QxMD MEDLINE Link].
Lupon J, Valle V, Marrugat J, et al. Six-month outcome in unstable angina patients without previous myocardial infarction according to the use of tertiary cardiologic resources. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempos de Espera. J Am Coll Cardiol. 1999 Dec. 34(7):1947-53. [QxMD MEDLINE Link].
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10. 361(11):1045-57. [QxMD MEDLINE Link].
Tanindi A, Erkan AF, Ekici B. Epicardial adipose tissue thickness can be used to predict major adverse cardiac events. Coron Artery Dis. 2015 Dec. 26 (8):686-91. [QxMD MEDLINE Link].
Karcz A, Holbrook J, Burke MC, et al. Massachusetts emergency medicine closed malpractice claims: 1988-1990. Ann Emerg Med. 1993 Mar. 22(3):553-9. [QxMD MEDLINE Link].
Li Z, Liu X, Wang J, et al. Analysis of urinary metabolomic profiling for unstable angina pectoris disease based on nuclear magnetic resonance spectroscopy. Mol Biosyst. 2015 Dec 10. 11 (12):3387-96. [QxMD MEDLINE Link].
Gurses KM, Kocyigit D, Yalcin MU, et al. Enhanced platelet toll-like receptor 2 and 4 expression in acute coronary syndrome and stable angina pectoris. Am J Cardiol. 2015 Dec 1. 116 (11):1666-71. [QxMD MEDLINE Link].
Meune C, Balmelli C, Twerenbold R, et al. Patients with acute coronary syndrome and normal high-sensitivity troponin. Am J Med. 2011 Dec. 124(12):1151-7. [QxMD MEDLINE Link].
Susilovic Grabovac Z, Bakovic D, Lozo M, Pintaric I, Dujic Z. Early changes in platelet size and number in patients with acute coronary syndrome. Int J Angiol. 2017 Dec. 26 (4):249-52. [QxMD MEDLINE Link].
Misra D, Leibowitz K, Gowda RM, Shapiro M, Khan IA. Role of N-acetylcysteine in prevention of contrast-induced nephropathy after cardiovascular procedures: a meta-analysis. Clin Cardiol. 2004 Nov. 27(11):607-10. [QxMD MEDLINE Link].
Calmarza P, Lapresta C, Martínez M, Lahoz R, Povar J. Utility of myeloperoxidase in the differential diagnosis of acute coronary syndrome. Arch Cardiol Mex. 2017 Dec 7. [QxMD MEDLINE Link].
Than M, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011 Mar 26. 377(9771):1077-84. [QxMD MEDLINE Link].
Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct. 33(20):2551-67. [QxMD MEDLINE Link]. [Full Text].
Januzzi JL, Cannon CP, DiBattiste PM, Murphy S, Weintraub W, Braunwald E. Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (The TACTICS-TIMI 18 Trial). Am J Cardiol. 2002 Dec 1. 90(11):1246-9. [QxMD MEDLINE Link].
Acara AC, Bolatkale M. Endothelial nitric oxide level as a predictor of coronary complexity in patients with unstable angina pectoris. Am J Med Sci. 2019 Feb 13. [QxMD MEDLINE Link].
[Guideline] Acute coronary syndrome and myocardial infarction. EBM Guidelines. Evidence-Based Medicine [internet]. Helsinki, Finland: Wiley Interscience. John Wiley & Sons; 2011. [Full Text].
de Zwaan C, Bar FW, Wellens HJ. Characteristic electrocardiographic pattern indicating a critical stenosis high in left anterior descending coronary artery in patients admitted because of impending myocardial infarction. Am Heart J. Apr 1982. ;103(4 Pt 2):730-6. [QxMD MEDLINE Link].
Nisbet BC, Zlupko G. Repeat Wellens' syndrome: case report of critical proximal left anterior descending artery restenosis. J Emerg Med. 2010 Sep. 39(3):305-8. [QxMD MEDLINE Link].
Kwong RY, Chan AK, Brown KA, et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation. 2006 Jun 13. 113(23):2733-43. [QxMD MEDLINE Link].
Kwong RY, Sattar H, Wu H, et al. Incidence and prognostic implication of unrecognized myocardial scar characterized by cardiac magnetic resonance in diabetic patients without clinical evidence of myocardial infarction. Circulation. 2008 Sep 2. 118(10):1011-20. [QxMD MEDLINE Link]. [Full Text].
Stratmann HG, Younis LT, Wittry MD, Amato M, Miller DD. Exercise technetium-99m myocardial tomography for the risk stratification of men with medically treated unstable angina pectoris. Am J Cardiol. 1995 Aug 1. 76(4):236-40. [QxMD MEDLINE Link].
Udelson JE, Spiegler EJ. Emergency department perfusion imaging for suspected coronary artery disease: the ERASE Chest Pain Trial. Md Med. 2001 Spring. Suppl:90-4. [QxMD MEDLINE Link].
Tegn N, Abdelnoor M, Aaberge L, et al, for the After Eighty study investigators. Health-related quality of life in older patients with acute coronary syndrome randomised to an invasive or conservative strategy. The After Eighty randomised controlled trial. Age Ageing. 2018 Jan 1. 47 (1):42-7. [QxMD MEDLINE Link].
[Guideline] Amsterdam EA, Wenger NK, Brindis RG, et all, for the ACC/AHA Task Force Members. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 23. 130(25):e344-426. [QxMD MEDLINE Link]. [Full Text].
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16. 345(7):494-502. [QxMD MEDLINE Link].
Beavers CJ, Naqvi IA. Clopidogrel. 2017 Jun. [QxMD MEDLINE Link]. [Full Text].
Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003 Oct 7. 108(14):1682-7. [QxMD MEDLINE Link].
Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 Nov 20. 288(19):2411-20. [QxMD MEDLINE Link].
Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22. 360(4):354-62. [QxMD MEDLINE Link].
Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010 Oct 28. 363(18):1704-14. [QxMD MEDLINE Link].
Park KW, Kim HS. Options to overcome clopidogrel response variability. Circ J. 2012. 76(2):287-92. [QxMD MEDLINE Link].
O'Connor FF, Shields DC, Fitzgerald A, Cannon CP, Braunwald E, Fitzgerald DJ. Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood. 2001 Dec 1. 98(12):3256-60. [QxMD MEDLINE Link].
De Servi S, Goedicke J, Schirmer A, Widimsky P. Clinical outcomes for prasugrel versus clopidogrel in patients with unstable angina or non-ST-elevation myocardial infarction: an analysis from the TRITON-TIMI 38 trial. Eur Heart J Acute Cardiovasc Care. 2014 Dec. 3(4):363-72. [QxMD MEDLINE Link].
Rudolph TK, Fuchs A, Klinke A, et al. Prasugrel as opposed to clopidogrel improves endothelial nitric oxide bioavailability and reduces platelet-leukocyte interaction in patients with unstable angina pectoris: A randomized controlled trial. Int J Cardiol. 2017 Dec 1. 248:7-13. [QxMD MEDLINE Link].
Effron MB, Nair KV, Molife C, et al. One-year clinical effectiveness comparison of prasugrel with ticagrelor: results from a retrospective observational study using an integrated claims database. Am J Cardiovasc Drugs. 2017 Dec 8. [QxMD MEDLINE Link].
US FDA approves expanded indication for BRILINTA to include long-term use in patients with a history of heart attack [press release]. AstraZeneca. September 3, 2015. Available at http://www.astrazeneca.com/Media/Press-releases/Article/20150903. Accessed: September 9, 2015.
Bonaca MP, Bhatt DL, Cohen M, et al, for the PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7. 372 (19):1791-800. [QxMD MEDLINE Link].
Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet. 2001 Jun 16. 357(9272):1915-24. [QxMD MEDLINE Link].
Ibbotson T, McGavin JK, Goa KL. Abciximab: an updated review of its therapeutic use in patients with ischaemic heart disease undergoing percutaneous coronary revascularisation. Drugs. 2003. 63(11):1121-63. [QxMD MEDLINE Link].
Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001 Dec 4. 104(23):2767-71. [QxMD MEDLINE Link].
Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Magee K. Heparin versus placebo for non-ST elevation acute coronary syndromes. Cochrane Database Syst Rev. 2014 Jun 27. 6:CD003462. [QxMD MEDLINE Link].
Cohen M, Demers C, Gurfinkel EP, et al. Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and safety of subcutaneous enoxaparin versus intravenous unfractionated heparin, in non-Q-wave coronary events. Am J Cardiol. 1998 Sep 10. 82(5B):19L-24L. [QxMD MEDLINE Link].
Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA. 2004 Jul 7. 292(1):45-54. [QxMD MEDLINE Link].
Mehta SR, Granger CB, Eikelboom JW, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol. 2007 Oct 30. 50(18):1742-51. [QxMD MEDLINE Link].
Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992 Jul 16. 327(3):141-5. [QxMD MEDLINE Link].
Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients' data. Lancet. 2002 Jan 26. 359(9303):294-302. [QxMD MEDLINE Link].
Metz BK, White HD, Granger CB, et al. Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators. J Am Coll Cardiol. 1998 Jun. 31(7):1493-8. [QxMD MEDLINE Link].
Maroo A, Lincoff AM. Bivalirudin in PCI: an overview of the REPLACE-2 trial. Semin Thromb Hemost. 2004 Jun. 30(3):329-36. [QxMD MEDLINE Link].
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006 Nov 23. 355(21):2203-16. [QxMD MEDLINE Link].
Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4. 285(13):1711-8. [QxMD MEDLINE Link].
Murphy SA, Cannon CP, Wiviott SD, McCabe CH, Braunwald E. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009 Dec 15. 54(25):2358-62. [QxMD MEDLINE Link].
US FDA. Safety: statin drugs - drug safety communication: class labeling change. US Food and Drug Administration. February 28, 2012. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm293670.htm. Accessed: June 5, 2013.
US FDA. Safety: Zocor (simvastatin): label change - new restrictions, contraindications, and dose limitations. US Food and Drug Administration. June 8, 2011. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258384.htm. Accessed: June 5, 2013.
US FDA. Safety: Meridia (sibutramine): market withdrawal due to risk of serious cardiovascular events. US Food and Drug Administration. October 8, 2010. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm. Accessed: June 5, 2013.
Soukoulis V, Boden WE, Smith SC Jr, O'Gara PT. Nonantithrombotic medical options in acute coronary syndromes: old agents and new lines on the horizon. Circ Res. 2014 Jun 6. 114(12):1944-58. [QxMD MEDLINE Link]. [Full Text].
Anderson HV, Cannon CP, Stone PH, et al. One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol. 1995 Dec. 26(7):1643-50. [QxMD MEDLINE Link].
Boden WE, O'Rourke RA, Crawford MH, et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. N Engl J Med. 1998 Jun 18. 338(25):1785-92. [QxMD MEDLINE Link].
Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet. 1999 Aug 28. 354(9180):708-15. [QxMD MEDLINE Link].
Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet. 2002 Sep 7. 360(9335):743-51. [QxMD MEDLINE Link].
Damman P, Hirsch A, Windhausen F, Tijssen JG, de Winter RJ. 5-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial a randomized comparison of an early invasive versus selective invasive management in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol. 2010 Mar 2. 55(9):858-64. [QxMD MEDLINE Link].
Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA. 2003 Sep 24. 290(12):1593-9. [QxMD MEDLINE Link].
Wallentin L, Lagerqvist B, Husted S, Kontny F, Stale E, Swahn E. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease. Lancet. 2000 Jul 1. 356(9223):9-16. [QxMD MEDLINE Link].
Sabatine MS, Giugliano RP, Keech AC, et al, for the FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4. 376 (18):1713-22. [QxMD MEDLINE Link]. [Full Text].
Szarek M, White HD, Schwartz GG, et al, for the ODYSSEY OUTCOMES Committees and Investigators. Alirocumab reduces total nonfatal cardiovascular and fatal events: The ODYSSEY OUTCOMES Trial. J Am Coll Cardiol. 2019 Feb 5. 73 (4):387-96. [QxMD MEDLINE Link]. [Full Text].
[Guideline] American Diabetes Association. Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. Clin Diabetes. 2016 Jan. 34 (1):3-21. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Collet JP, Thiele H, Barbato E, et al, for the ESC Scientific Document Group . 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020 Aug 29. ehaa575. [QxMD MEDLINE Link]. [Full Text].
Zoler ML. ESC’s revised NSTE-ACS guidelines embrace hsT, personalized anti-ischemia treatments. Medscape Medical News. September 1, 2020. Available at https://www.medscape.com/viewarticle/936676. Accessed: September 28, 2020.
[Guideline] Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14. 37 (3):267-315. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Isc... Circulation. 2016 Mar 29. [QxMD MEDLINE Link]. [Full Text].
Amgen Inc. FDA approves Amgen's Repatha (evolocumab) to prevent heart attack and stroke. Available at https://www.amgen.com/media/news-releases/2017/12/fda-approves-amgens-repatha-evolocumab-to-prevent-heart-attack-and-stroke/. December 1, 2017; Accessed: December 5, 2017.
Sanofi-Aventis. FDA approves Praluent (alirocumab) to prevent heart attack, stroke and unstable angina requiring hospitalization [press release]. Available at http://www.news.sanofi.us/2019-04-26-FDA-approves-Praluent-R-alirocumab-to-prevent-heart-attack-stroke-and-unstable-angina-requiring-hospitalization. April 26, 2019; Accessed: April 30, 2019.
Busko M. New non-ST-elevation ACS guidelines: new title, new approach. Medscape Medical News from WebMD. September 29, 2014. Available at http://www.medscape.com/viewarticle/832513. Accessed: October 4, 2014.
Eggers KM, Jernberg T, Lindahl B. Unstable angina in the era of cardiac troponin assays with improved sensitivity-a clinical dilemma. Am J Med. 2017 Dec. 130 (12):1423-30.e5. [QxMD MEDLINE Link].
Nowak R, Mueller C, Giannitsis E, et al. High sensitivity cardiac troponin T in patients not having an acute coronary syndrome: results from the TRAPID-AMI study. Biomarkers. 2017 Dec. 22 (8):709-14. [QxMD MEDLINE Link].
Rottger E, de Vries-Spithoven S, Reitsma JB, et al. Safety of a 1-hour rule-out high-sensitive troponin T protocol in patients with chest pain at the emergency department. Crit Pathw Cardiol. 2017 Dec. 16 (4):129-34. [QxMD MEDLINE Link].
Driscoll A, Barnes EH, Blankenberg S, et al. Predictors of incident heart failure in patients after an acute coronary syndrome: The LIPID heart failure risk-prediction model. Int J Cardiol. 2017 Dec 1. 248:361-8. [QxMD MEDLINE Link].

Media Gallery

Pathogenesis of acute coronary syndromes.
Thrombolysis in Myocardial Infarction (TIMI) Risk Score correlates with major adverse outcome and effect of therapy with low-molecular-weight heparin. ARD = absolute risk difference; ESSENCE = Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events; No. = number; NNT = number needed to treat.
Algorithm for initial invasive strategy. ASA = acetylsalicylic acid (aspirin); GP IIb/IIIa= glycoprotein IIb/IIIa; IV = intravenous; LOE = level of evidence; UA/NSTEMI = unstable angina/non–ST-segment elevation myocardial infarction; UFH = unfractionated heparin. (Adapted from 2007 ACC/AHA UA/NSTEMI Guidelines.)
Algorithm for initial conservative strategy. ASA = acetylsalicylic acid (aspirin); EF = ejection fraction; GP IIb/IIIa= glycoprotein IIb/IIIa; IV = intravenous; LOE = level of evidence; LVEF = left ventricular ejection fraction; UA/NSTEMI = unstable angina/non–ST-segment elevation myocardial infarction. (Adapted from 2007 ACC/AHA UA/NSTEMI Guidelines.)
Rate and timing of revascularization for patients with unstable angina using invasive versus conservative approach (FRagmin during InStability in Coronary artery disease [FRISC] II).
Time course of elevations of serum markers after acute myocardial infarction. CK = creatine kinase; CK-MB = creatine kinase MB fraction; LDH = lactate dehydrogenase.

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Table 1. Patient Characteristics, GUARANTEE Versus CRUSADE Trials

Characteristics	GUARANTEE, 1995-96 ^[12]	CRUSADE, 2001-06 ^[13]
Mean age (y)	62	69
Patients >65 y (%)	44	–
Female (%)	39	40
Hypertension (%)	60	73
Diabetes mellitus (%)	26	33
Current smoker (%)	25	–
Hypercholesterolemia (%)	43	50
Previous stroke (%)	9	–
Previous MI (%)	36	30
Previous angina (%)	66	–
CHF (%)	14	18
Previous coronary intervention (%)	23	21
Previous coronary bypass surgery (%)	25	19
CHF = congestive heart failure; CRUSADE = Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines; GUARANTEE = Global Unstable Angina Registry and Treatment Evaluation; MI = myocardial infarction.

Table 2. Demographic Characteristics of Patients in International OASIS-2 Registry

Characteristics ^[15]		Australia	Brazil	Canada	Hungary	Poland	United States
General	Number of patients	1899	1478	1626	931	1135	918
	Mean age (y)	65	62	66	65	63	66
	Women (%)	37	42	37	45	40	37
Clinical	NQMI presentation (%)	7	7	14	22	17	16
Clinical	Abnormal ECG (%)	74	91	82	95	97	87
Select treatments	Beta blocker (%)	67	53	73	67	59	57
Select treatments	Calcium blocker (%)	59	51	53	52	43	59
Invasive procedures (index hospitalization)	Cardiac catheterization (%)	24	69	43	20	7	58
	PCI (%)	7	19	16	5	0.4	24
	CABG (%)	4	20	10	7	0.4	17
CABG = coronary artery bypass grafting; ECG = electrocardiographic; NQMI = non-Q wave myocardial infarction; OASIS = Organization to Assess Strategies for Ischemic Syndromes; PCI = percutaneous coronary intervention.

Table 3. Thirty-Day Clinical Outcome in Patients With Acute Coronary Syndromes in Clinical Trials

Study	Year	Number of Patients	Death (%)	Myocardial Infarction (%)	Major Bleed (%)
TIMI-3	1994	1,473	2.5	9.0	0.3
GUSTO-IIb	1997	8,011	3.8	6.0	1.0
ESSENCE	1998	3,171	3.3	4.5	1.1
PARAGON-A	1998	2,282	3.2	10.3	4.0
PRISM	1998	3,232	3.0	4.2	0.4
PRISM-PLUS	1998	1,915	4.4	8.1	1.1
PURSUIT	1998	10,948	3.6	12.9	2.1
TIMI-11B	1999	3,910	3.9	6.0	1.3
PARAGON-B	2000	5,225	3.1	9.3	1.1
Pooled		40,167	3.5	8.5	1.5
ESSENCE = Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events; GUSTO-IIb = Global Utilization of Streptokinase and TPA (tissue plasminogen activator) for Occluded Coronary Arteries; PARAGON-A = Platelet IIb/IIIa Antagonism (lamifiban) for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network; PARAGON-B = Platelet IIb/IIIa Antagonism (lamifiban) for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network; PRISM = Platelet Receptor Inhibition in Ischemic Syndrome Management; PRISM-PLUS = Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Angina Signs and Symptoms; PURSUIT = Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy; TIMI-11B = Thrombolysis in Myocardial Infarction Clinical Trial 11B; TIMI-3 = Thrombolysis in Myocardial Infarction Clinical Trial 3.

Table 4. Braunwald Classification of Unstable Angina

Characteristic	Class/Category	Details
Severity	I	Symptoms with exertion
	II	Subacute symptoms at rest (2-30 days prior)
	III	Acute symptoms at rest (within prior 48 hr)
Clinical precipitating factor	A	Secondary
	B	Primary
	C	Postinfarction
Therapy during symptoms	1	No treatment
	2	Usual angina therapy
	3	Maximal therapy

Table 5. Recommendations for Selection of Preferred Management Strategy

Preferred Strategy	Patient Characteristic/Clinical Risk
Immediate Invasive Strategy (< 2 hours)	Refractory angina
	Signs/symptoms of heart failure or new or worsening mitral regurgitation
	Hemodynamic instability or cardiogenic shock
	Recurrent angina/ischemia at rest or with low-level activities despite intensive medical therapy
	Sustained ventricular tachycardia or ventricular fibrillation
Ischemia-Guided Strategy	Low-risk score (eg, TIMI 0 or 1, GRACE < 109)
	Low-risk Tn-negative female
	Patient or physician preference in the absence of high-risk features
Early Invasive Strategy (< 24 hours)	GRACE score >140
	Rise or fall in Tn compatible with myocardial infarction
	New or presumably new ST-segment depression
Delayed Invasive Strategy (24-72 hours)	Diabetes mellitus
	Renal insufficiency (GFR < 60 mL/min/1.73m²)
	Reduced LV systolic function (LVEF < 40%)
	Early postinfarction angina
	PCI within 6 months
	Prior CABG
	GRACE score 109-140; TIMI Score ≥2
ACC/AHA = American College of Cardiology/American Heart Association; CABG = coronary artery bypass grafting; GFR = glomerular filtration rate; GRACE = Global Registry of Acute Coronary Events; LV = left ventricle; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis in Myocardial Infarction Clinical Trial; Tn = troponin.

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Author

Walter Tan, MD, MS Associate Professor of Medicine, Wake Forest University School of Medicine; Director of Cardiac Cath Labs, Wake Forest Baptist Medical Center

Walter Tan, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American College of Cardiology, American Heart Association, American Stroke Association, National Stroke Association, Society for Vascular Medicine, Society of Interventional Radiology

Disclosure: Nothing to disclose.

Coauthor(s)

David J Moliterno, MD Professor of Medicine, Jefferson Morris Gill Professor of Cardiology, Chief, Division of Cardiovascular Medicine, University of Kentucky; Vice Chairman of Internal Medicine, Chandler Medical Center; Medical Director, Gill Heart Institute

David J Moliterno, MD is a member of the following medical societies: American College of Cardiology, European Society of Cardiology, Association of Professors of Cardiology, American College of Physicians, American Heart Association, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Richard A Lange, MD, MBA President, Texas Tech University Health Sciences Center, Dean, Paul L Foster School of Medicine

Richard A Lange, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, Association of Subspecialty Professors

Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD Associate Professor of Medicine, Director of Cardiac Catherization Laboratory and Interventional Cardiology, Mayo Clinic ArizonA

Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Acknowledgements

Steven James Filby, MD Fellow in Interventional Cardiology, The Cleveland Clinic Foundation

Disclosure: Nothing to disclose.

Justin D Pearlman, MD, ME, PhD, FACC, MA Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Director of Cardiology Quality Program KMC, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School

Justin D Pearlman, MD, ME, PhD, FACC, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Unstable Angina Guidelines

Acute Coronary Syndromes Clinical Practice Guidelines (ESC, 2020)

2014 AHA/ACC and 2015 ESC Guidelines for the Management NSTE-ACS

Evaluation

Selection of management strategy

Initial hospital care

Antiplatelet therapy

Dual antiplatelet therapy

Hospital discharge and follow-up

Diabetes

References

Tables

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