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Management of acute coronary syndrome 

Management of acute coronary syndrome

Chapter:
Management of acute coronary syndrome
Author(s):

Keith A.A. Fox

and Rajesh K. Kharbanda

DOI:
10.1093/med/9780199204854.003.161305_update_003

Update:

Role of anti-Xa inhibitors (Fondaparinux) and bivalirudin in ACS management. This chapter now includes content from retired Chapter 16.13.8.

Updated on 29 Oct 2015. The previous version of this content can be found here.
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date: 28 March 2017

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. Clinical presentation with an ACS identifies a patient at high risk of further cardiovascular events requiring a defined acute and long-term management strategy.

The choice and timing of acute 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 is recommended in those patients with evidence of desaturation, particularly in those who are breathless or who have 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 ACS 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) P2Y12 receptor inhibitor, e.g. ticagrelor, parsugrel, or clopidogrel; (c) unfractionated or low molecular weight heparin (LMWH), or a direct thrombin inhibitor, e.g. bivalirudin; and (d) glycoprotein IIb/IIIa inhibition, e.g. abciximab, eptifibatide, and tirofiban. (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 haemodynamic support (e.g. intra-aortic balloon pump to reduce ischaemia and stabilize the patient for revascularization).

Where the clinical features support a diagnosis of a primary ACS, patients developing ST elevation require emergency assessment with coronary angiography and where appropriate reperfusion by primary PCI, or—when a primary angioplasty service 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 P2Y12 receptor inhibitor, e.g. ticagrelor, parsugrel, or 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 assessment of the cardiovascular risk and stress testing or perfusion scanning to identify the presence and extent of inducible ischaemia, 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 only be employed with β‎-blockers in ACS 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 ACS unless there is good evidence of aspirin allergy or evidence of active bleeding; (2) P2Y12 receptor inhibitor��patients with non-ST-elevation ACS should be given a loading dose of either ticagrelor 180 mg, prasugrel 60 mg, or clopidogrel 300–600 mg, followed by continued treatment, in combination with aspirin. Dual antiplatelet therapy (DAPT) should be maintained for 12 months, unless the risks of bleeding exceed potential benefits. Following PCI, the duration of DAPT administration should take account of the type of stent implanted (bare metal or drug-eluting) and the risks of bleeding/thrombosis; Ticagrelor, a nonthienopyridine P2Y12 platelet antagonist, 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-coronary artery bypass grafting (CABG) bleeding was increased. 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. They should be administered with oral antiplatelet agents (aspirin and P2Y12 receptor inhibitor) and anticoagulants (see next paragraph).

Anticoagulation—this is required in addition to antiplatelet therapy. Indirect thrombin inhibitors: LMWH is better than unfractionated heparin (UFH) 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. Bilvalirudin is the only direct thrombin inhibitor currently used in ACS management.

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 PCI 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, reinfarction, 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 120 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 prehospital 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 ACS unless there is good evidence of aspirin allergy or evidence of active bleeding. (2) P2Y12 receptor inhibitors (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) Anticoagulants—bivalirudin is indicated in patients managed with primary PCI. Patients treated with fibrinolytic therapy should receive LMWH or fondaparinux (a factor Xa inhibitor). (4) GPIIb/IIIa inhibitors-e.g. abciximab, eptifibatide, tirofiban—are indicated in patients managed with primary PCI, but not in those managed with fibrinolysis.

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. (5) Aldostrone blockade (e.g. epleronone) in those with left vntricular ejection fraction (LVEF) <35% and diabetes or clinical features of heart failure.

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