Acute Treatment and Prevention of ACS

Pharmacologic or interventional treatments, or both, may be used

Acute coronary syndrome (ACS) is triggered by the rupture or ulceration of an intracoronary atherosclerotic plaque. When the endothelium is breached, blood comes in contact with plaque that is rich in tissue-factor, leading to thrombus formation.⁵

Thrombi formed in this manner cause variable degrees of obstruction in the coronary artery and subsequent myocardial ischaemia. Complete coronary artery obstruction generally leads to an ST-elevation myocardial infarction (STEMI).⁸³ The standard of care for this medical emergency is treatment with the goal of achieving reperfusion. This can be attempted pharmacologically, with thrombolytic therapy (ie, fibrinolytic medications, such as tissue plasminogen activator), or mechanically, using percutaneous coronary intervention (PCI) or coronary artery bypass surgery. The decision to attempt immediate reperfusion in patients with non-ST-elevation ACS is based on risk stratification.⁸³

The goal of treatment: stabilisation and prevention of recurrence

For all ACS patients, including patients with unstable angina as well as those suffering a myocardial infarction (MI), principles of care include stabilisation of the acute coronary artery lesion, relief of cardiac ischaemia, and long-term measures to prevent recurrent arterial thrombotic events, such a recurrent ACS or stroke.¹²⁹

Platelet-rich thrombi tend to form under conditions of high-shear stress, as occurs in arterial circulation. For this reason, antiplatelet agents are an essential component in the treatment of ACS to suppress platelet activation as the coronary lesion evolves. The course of recovery in ACS involves spontaneous, mechanical, or pharmacologic thrombolysis. Clot lysis is associated with hypercoagulability, as thrombin molecules are exposed during the process. This sets the stage for recurrent thrombosis and possible vessel reocclusion. For this reason, anticoagulant therapy is critical during the acute phase of treatment. The combination of antiplatelet and anticoagulant therapy is more effective than either strategy alone.^{23, 129}

In patients without contraindications, acute care often includes dual antiplatelet therapy with Aspirin and clopidogrel. Parenteral glycoprotein IIb/IIIa inhibitors provide additional protection against platelet aggregation, particularly in those undergoing PCI. Unfractionated heparin or low-molecular-weight heparin is generally used for anticoagulation. Fondaparinux has also been successfully studied for use in ACS. Other anticoagulant options for use during PCI include the direct thrombin inhibitors bivalirudin and argatroban.^{23, 106}

Secondary prevention is essential

Patients who experience an episode of ACS often have atherosclerosis affecting other coronary arteries or peripheral or cerebral arteries. For this reason, secondary prevention is an important facet of long-term care.¹²⁹ Drugs from several classes have been shown to reduce risk, including antiplatelet agents, ACE inhibitors, statins, and beta-blockers.²³ These medications work by decreasing shear stress in the arteries, affecting the properties of the arterial wall, or slowing the progression of atherosclerosis.

Lifelong therapy with low-dose Aspirin is generally recommended for patients without contraindications (such as GI bleeding). Dual antiplatelet therapy with Aspirin and clopidogrel is recommended for at least one month, and preferably for a year, following the acute event, particularly in those treated with drug-eluting stents.^{83, 95} Long-term oral anticoagulation with a vitamin K antagonist is more effective than Aspirin alone, but it has a greater risk of bleeding, so this treatment is generally limited to patients with atrial fibrillation or to those who develop a left-ventricular thrombus after an MI.^{129, 130}

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Article references

5 - Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol. 2005;46(6):937-954.
83 - Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007;116(7):e148-e304.
129 - Gelfand EV, Cannon CP. Acute Coronary Syndrome. In: Colman RW, Clowes AW, George JN, Goldhaber SZ, Marder VJ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006:1387-1404.
23 - Bassand JP, Hamm CW, Ardissino D, et al; Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28(13):1598-1660.
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95 - Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008;451(7181):914-918.
130 - Smith SC Jr, Allen J, Blair SN, et al; AHA/ACC; National Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113(19):2363-2372.

Acute coronary syndrome: This is an umbrella term used to cover any group of clinical symptoms compatible with acute myocardial ischaemia (chest pain due to insufficient blood supply to the heart muscle that results from coronary artery disease). Acute coronary syndrome covers the spectrum of clinical conditions ranging from unstable angina to STEMI and NSTEMI.
Myocardial infarction: Destruction of heart tissue due to reduced blood flow to the heart. Also known as a heart attack. It usually results from coronary artery disease and is more severe than angina.
Angina: Heart condition characterised by intermittent chest pain. Angina usually results from coronary artery disease and may further be classified as stable or unstable angina. Stable angina refers to the more common understanding of angina related to myocardial ischemia. Unstable angina may occur unpredictably at rest which may be a serious indicator of an impending heart attack.
Hypercoagulability: A potentially dangerous state of an increased tendency for blood to coagulate, even within blood vessels. Hypercoagulability can be an inherited condition (e.g., Factor V Leiden mutation) or acquired through circumstance (e.g., cancer).
Platelet: (Thrombocyte) Cell circulating in the blood that is involved in the cellular mechanisms of primary haemostasis leading to the formation of blood clots. When a blood vessel is injured, platelets gather at the site of injury and stick together to form a plug, thereby preventing blood loss.
Thrombin: Also called Factor IIa, thrombin performs two functions in the coagulation cascade: activating platelets, and catalysing the conversion of soluble fibrinogen into insoluble fibrin. It is formed from prothrombin by a reaction that is catalysed by Factor Xa.
Aspirin: The brand name of acetylsalicylic acid (ASA), an antithrombotic medication that prevents thrombosis by inhibiting the activity of platelets – a component of blood that helps to prevent blood loss.
Clopidogrel: Oral antiplatelet agent used in the treatment of coronary artery disease, peripheral vascular disease and cerebrovascular disease.
Fondaparinux: An indirect Factor Xa inhibitor comprising a synthetic pentasaccharide sequence matching the part of the heparin molecule that binds to antithrombin. It is administered by subcutaneous injection.
Heparin: An anticoagulant that exerts its activity by binding to antithrombin and greatly increasing its activity. The principal coagulation factors inhibited by heparin are Factors IIa and Xa. It is administered by intravenous or subcutaneous injection.
Parenteral: Not through the alimentary canal but rather by injection through another route.
Angiotensin-converting enzyme: Hydrolase enzyme that cleaves angiotensin I (biologically inactive) to form active angiotensin II. The inhibition of ACE is used for the treatment of high blood pressure, heart failure, diabetic nephropathy, and to delay type 2 diabetes mellitus.
Vitamin K: An essential cofactor in the carboxylation of glutamic residues on the procoagulant forms of Factors II, VII, IX, and X. This ultimately leads to increased formation of thrombin and fibrin.