Chapter

Management of acute coronary syndrome

Keith A.A. Fox and Nicholas L. Mills

in Oxford Textbook of Medicine

Fifth edition

Published on behalf of Oxford University Press

Published in print May 2010 | ISBN: 9780199204854
Published online November 2011 | e-ISBN: 9780199570973 | DOI: http://dx.doi.org/10.1093/med/9780199204854.003.161305_update_002

Series: Oxford Textbooks

Management of acute coronary syndrome

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The acute coronary syndrome (ACS) is precipitated by an abrupt change in an atheromatous plaque, resulting in increased obstruction to perfusion and ischaemia or infarction in the territory supplied by the affected vessel. The clinical consequences of plaque rupture can range from an entirely silent episode, through to unstable symptoms of ischaemia without infarction, to profound ischaemia complicated by progressive infarction, heart failure, and risk of sudden death.

The choice and timing of management strategy is critically dependent on the extent and severity of myocardial ischaemia, with the spectrum of ACS broken down into three elements: (1) Unstable angina: typical ischaemic symptoms without ST elevation on ECG and without elevated biomarkers of necrosis. (2) Non-ST-elevation myocardial infarction (MI): typical ischaemic symptoms without ST elevation on ECG but with biomarkers of necrosis above the diagnostic threshold. (3) ST-elevation MI: typical ischaemic symptoms with ST elevation on ECG and with biomarkers of necrosis above the diagnostic threshold.

An acute reperfusion strategy (primary percutaneous coronary intervention (PCI) or thrombolysis) is of proven benefit only in ST segment elevation infarction (or MI with new bundle branch block).

Prompt relief of pain is important, not only for humanitarian reasons, but also because pain is associated with sympathetic activation, vasoconstriction, and increased myocardial work. Effective analgesia is best achieved by the titration of intravenous opioids, with concurrent administration of an antiemetic. High-flow oxygen should be given, especially to those who are breathless or those with any features of heart failure or shock.

The management of prehospital cardiac arrest requires special attention: at least as many lives can be saved by prompt resuscitation and defibrillation as by reperfusion. Patients may also require management of arrhythmic and haemodynamic complications, including heart failure.

Acute coronary syndromes without ST elevation (unstable angina/non-ST elevation MI)

Patients without ST elevation or left bundle branch block can be triaged into low, intermediate, and high-risk categories. (1) High-risk—patients with typical clinical features of ischaemia and ST-segment depression or transient ST-segment elevation, or with troponin elevation and a high-risk score (Risk calculator downloadable from http://www.outcomes.org/grace or http://www.timi.org/). Patients are also at high risk when ischaemia provokes arrhythmias or haemodynamic compromise. (2) Intermediate or low risk—patients with clinical features of acute coronary syndrome and nonspecific ECG changes (T wave inversion, T wave flattening, minor conduction abnormalities, etc.). (3) Low risk or an alternative diagnosis—patients with a normal ECG, normal biomarkers, normal cardiac examination, and normal echo.

Patients at high risk—(1) High-risk patients with acute ischaemia at initial presentation, or those who develop such features after hospital admission, and especially those with haemodynamic compromise, require emergency assessment for revascularization and potentially benefit from glycoprotein IIb/IIIa inhibition. (2) Those proceeding to emergency revascularization should receive (a) aspirin; (b) thienopyridine, e.g. clopidogrel; (c) glycoprotein IIb/IIIa inhibition, e.g. abciximab, eptifibatide, and tirofiban; and (d) unfractionated or low molecular weight heparin (LMWH), or a direct thrombin inhibitor, e.g. bivalirudin. (3) Some patients should receive anti-ischaemic therapy (e.g. nitrates, β-blockers, calcium entry blockers, potassium channel activators, etc.), and some will require antiarrhythmic management or haemodymamic support (e.g. intra-aortic balloon pump to reduce ischaemia and stabilize the patient for revascularization).

Patients developing ST elevation require emergency reperfusion by primary percutaneous coronary intervention (PCI), or—if PCI is not available—by thrombolysis (see below).

Patients at intermediate or low risk—patients with non-ST-elevation ACS and an intermediate risk score require dual antiplatelet therapy (aspirin plus thienopyridine, e.g. clopidogrel) plus anticoagulation (e.g. heparin, LMWH, fondaparinux, or bivalirudin). They are candidates for an early elective revascularization strategy (within c.72 h).

Clinically stable patients with minor or nonspecific ECG abnormalities and a low risk score (including negative repeat troponin) are at very low risk for in-hospital, major cardiac events. Such patients may, nevertheless, have significant underlying coronary artery disease. They require stress testing or perfusion scanning, ideally prior to discharge.

Specific interventions—anti-ischaemic therapies—(1) nitrates—effective in reducing ischaemia in the in-hospital management of non-ST elevation ACS, but there is no evidence that they improve mortality; (2) β-blockers—patients with suspected acute coronary syndromes should be initiated on β-blocker therapy unless contraindicated; (3) dihydropyridine calcium entry blockers—should be employed with β-blockers in acute coronary syndromes to avoid reflex tachycardia. In patients unable to tolerate β-blockers, a heart-rate-slowing calcium antagonist, e.g. diltiazem or verapamil, may be appropriate. Short-acting dihydropyridines should not be used in isolation in ACS.

Antiplatelet therapies—(1) aspirin 75–325 mg daily—indicated in all patients with acute coronary syndromes unless there is good evidence of aspirin allergy or evidence of active bleeding; (2) thienopyridine—patients with non-ST-elevation ACS should be given clopidogrel as an initial 300-mg loading dose, followed by continued treatment at a dose of 75 mg daily, in combination with aspirin. Clopidogrel should be given alone to patients with contraindications to aspirin (same regimen). Clopidogrel should be maintained for 12 months, unless the risks of bleeding exceed potential benefits. In patients undergoing PCI, a loading dose of 600 mg of clopidogrel may be used to achieve more rapid inhibition of platelet function. Following PCI, the duration of clopidogrel administration should take account of the type of stent implanted (bare metal or drug-eluting) and the risks of bleeding/thrombosis; Prasugrel is a more potent thienopyridine than clopidogrel (TRITON Study) and has improved outcomes (mainly reduced MI), especially in diabetics. It results in fewer stent thromboses. However there is more bleeding, and it should be avoided in patients with previous intracerebral bleeding or transient ischaemic attack. (3) GPIIb/IIIa inhibitors—e.g. abciximab, eptifibatide, tirofiban—result in improved outcome in patients requiring urgent percutaneous intervention for non-ST-segment-elevation ACS and in those at intermediate to high risk. Should be administered with oral antiplatelet agents (aspirin and thienopyridines) and anticoagulants (heparin or LMWH). Ticagrelor, a non thienopyridine P2Y12 platelet antagonist also has improved outcomes compared with clopidogrel (fewer infarctions and fewer deaths and fewer stent thromboses) (PLATO study). Overall rates of bleeding were not increased but non-CABG bleeding was increased. It has been approved by the European Medicines Agency, but has not yet been approved for use in the United States.

Anticoagulation—this is required in addition to antiplatelet therapy. LMWH is better than unfractionated heparin and is most commonly used. In the absence of an urgent/early invasive strategy, fondaparinux (a synthetic pentasaccharide that selectively binds antithrombin and causes inhibition of factor Xa) has the most favourable efficacy/safety profile.

ST-segment-elevation myocardial infarction

Patients with clear-cut evidence of ST-elevation infarction (STEMI) require immediate triage to reperfusion therapy. ‘Fast-track’ systems have been developed to minimize in-hospital delay to reperfusion: these aim to achieve clinical assessment and electrocardiography within 15 min of arrival and rapid transfer for percutaneous coronary intervention or the institution of thrombolytic therapy within 30 min. Audit programmes and continuous training are necessary for centres to achieve this 30-min median ‘door-to-needle’ time.

PCI—Randomized clinical trials of primary PCI vs thrombolysis have shown consistent findings: primary PCI is better, providing more effective restoration of vessel patency, achieving better ventricular function, and improving important clinical outcomes with lower rates of death, re-infarction, stroke, major bleeding, and recurrent ischaemia. Particular gains are seen in haemodynamically compromised patients. In consequence, primary PCI is the preferred therapeutic option in national and international guidelines.

Thrombolysis—prehospital thrombolysis is the next best option if a primary PCI programme is not available, or if transfer times are sufficiently prolonged that reperfusion may not be achieved within 90 min of patient call.

The current reference standard for the comparison of fibrinolytic agents is the accelerated infusion regimen of alteplase (tPA), or—for simplicity—the single-bolus administration of tenecteplase (TNK), which does not require an infusion pump or refrigeration and hence is particularly suited for pre-hospital administration. Internationally, streptokinase remains the most widely used fibrinolytic agent, principally because it is relatively inexpensive.

Antiplatelet agents and anticoagulants—(1) Aspirin 75–325 mg daily—indicated in all patients with acute coronary syndromes unless there is good evidence of aspirin allergy or evidence of active bleeding. (2) Thienopyridine—clopidogrel (regimen as described above) should be given to all patients, continuing for at least 1 month in patients managed with fibrinolysis (or as determined by the type of stents implanted). (3) GP IIb/IIIa inhibitors—e.g. abciximab, eptifibatide, tirofiban—are indicated in patients managed with primary PCI, but not in those managed with fibrinolysis. (4) Anticoagulants—patients treated with fibrinolytic therapy should receive LMWH or fondaparinux (a factor Xa inhibitor).

Secondary prevention measures in patients with ACS

Patients require advice and help regarding cessation of smoking (including the avoidance of passive smoking), dietary modification, exercise, rehabilitation, and management of obesity.

The following therapies have been shown to reduce the risk of subsequent cardiovascular events: (1) antiplatelet therapy—aspirin in a dose of 75 mg/day, clopidogrel 75 mg/day; (2) β-blockers in those without contraindications; (3) lipid lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins); (4) angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB), especially in those with left ventricular dysfunction and heart failure, and benefit is also possible in other patients with vascular disease.

Chapter.  21639 words.  Illustrated.

Subjects: Cardiovascular Medicine

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