Acute Treatment and Prevention of ACS

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

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 as 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}

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 is associated with 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}