Acute Coronary Syndrome Medication
- Author: David L Coven, MD, PhD; Chief Editor: Eric H Yang, MD more...
Medication Summary
The goals of treatment are to preserve patency of the coronary artery, augment blood flow through stenotic lesions, and reduce myocardial oxygen demand. All patients should receive antiplatelet agents, and patients with evidence of ongoing ischemia should receive aggressive medical intervention until signs of ischemia, as determined by symptoms and ECG, resolve.
Antiplatelet agents
Class Summary
Antiplatelets inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, which is a potent platelet activator. Antiplatelet therapy reduces mortality by reducing the risk of fatal strokes and fatal myocardial infarctions.
Aspirin (Anacin, Ascriptin, Bayer Aspirin)
Early administration of aspirin (eg, Anacin, Ascriptin, Bayer Aspirin) in patients with acute myocardial infarction may reduce cardiac mortality in the first month. The adult dose is 160-324 mg PO or chewed. It can be administered as a suppository if the patient is unable to take PO medications. Aspirin reduces morbidity and mortality and is continued indefinitely. If administered with ticagrelor (Brilinta), do not exceed 100 mg/day after a one-time loading dose of 325 mg.
Nitrates
Class Summary
Nitrates oppose coronary artery spasm and reduce myocardial oxygen demand by reducing preload and afterload.
Nitroglycerin topical (Nitro-Bid)
Nitroglycerin (Nitro-Bid) causes relaxation of the vascular smooth muscle via stimulation of intracellular cyclic guanosine monophosphate production, causing a decrease in blood pressure. Nitrates do not improve mortality.[56] However, they provide symptomatic relief by means of several mechanisms, including coronary vasodilation, improved collateral blood flow, decrease in preload (venodilation and reduced venous return), and decrease in afterload (arterial vasodilation). Care should be taken to avoid hypotension, because this can potentially reduce coronary perfusion pressure (diastolic BP - LV diastolic pressure).
Analgesics
Class Summary
These agents reduce pain which decreases sympathetic stress, in addition to providing some preload reduction.
Morphine sulfate (Duramorph, Astramorph, MS Contin)
Morphine sulfate (Duramorph, Astramorph, MS Contin) is the drug of choice for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered intravenously may be dosed in a number of ways and commonly titrated until the desired effect is obtained.
Beta-adrenergic blockers
Class Summary
Beta blockers have antiarrhythmic and antihypertensive properties, as well as the ability to reduce ischemia. They minimize the imbalance between myocardial supply and demand by reducing afterload and wall stress. In patients with acute MI, they decrease infarct size as well as short- and long-term mortality, which is a function of their anti-ischemic and antiarrhythmic properties. These drugs may prevent mechanical complications of myocardial infarction, including rupture of the papillary muscle, left ventricular free wall, and ventricular septum. Beta blockers ameliorate dynamic obstruction of the left ventricular outflow tract in patients with apical infarct and hyperdynamic basal segments. They should not be used acutely in patients with cardiogenic shock or signs of heart failure on presentation.
Metoprolol (Lopressor)
Metoprolol (Lopressor) is a selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions. During IV administration, blood pressure, heart rate, and ECG should be carefully monitored. The goal of treatment is to reduce the patient's heart rate to 60-90 beats/min.
Esmolol (Brevibloc)
Esmolol (Brevibloc) is an excellent drug for use in patients at risk for complications from beta blockers, particularly reactive airway disease, mild to moderate LV dysfunction, and peripheral vascular disease. Its short half-life of 8 min allows for titration to desired effect with the ability to stop quickly prn.
Glycoprotein IIB/IIIA inhibitors
Class Summary
Glycoprotein IIb/IIIa receptor antagonists include abciximab[69, 70] , eptifibatide[71] , and tirofiban[72] . Glycoprotein IIb/IIIa antagonists prevent the binding of fibrinogen, thereby blocking platelet aggregation. These drugs inhibit the glycoprotein IIb/IIIa receptor, which is involved in the final common pathway for platelet adhesion and aggregation. Currently, GP IIb/IIIb receptor antagonists in combination with aspirin are considered standard antiplatelet therapy for patients at high risk for unstable angina.
Abciximab (ReoPro)
Abciximab (ReoPro) is a chimeric human-murine monoclonal antibody. It binds to receptors with high affinity and reduces platelet aggregation by 80%. Inhibition of platelet aggregation persists for up to 48 hours after the end of infusion. Abciximab has been approved for use in elective/urgent/emergent percutaneous coronary intervention.
Eptifibatide (Integrilin)
Eptifibatide (Integrilin) is an antagonist of the platelet GP IIb/IIIa receptor; it reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor. The end effect is the inhibition of platelet aggregation. The effects persist over the duration of maintenance infusion and are reversed when infusion ends. Use eptifibatide (or tirofiban, see below) in patients with high-risk features in whom invasive treatment is not planned.
Tirofiban (Aggrastat)
Tirofiban (Aggrastat) is a nonpeptide antagonist of the GP IIb/IIIa receptor. It is a reversible antagonist of fibrinogen binding. When administered intravenously, more than 90% of platelet aggregation is inhibited. Tirofiban has been approved for use in combination with heparin for patients with unstable angina who are being treated medically and for patients undergoing percutaneous coronary intervention.
Anticoagulants
Class Summary
Anticoagulants are used to prevent recurrence of clot after a spontaneous fibrinolysis.
Heparin
Heparin augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. This agent prevents recurrence of a clot after spontaneous fibrinolysis.
Low molecular weight heparins
Class Summary
LMWH is indicated for treatment of ST-segment elevation myocardial infarction (STEMI) managed medically or with subsequent PCI. It is also indicated as prophylaxis for ischemic complications caused by unstable angina and non–Q-wave myocardial infarction.
Aside from the possible medical benefits of using LMWH in place of unfractionated heparin, advantages of LMWH include ease of administration, absence of need for anticoagulation monitoring, and potential for overall cost savings. Although 3 LMWHs are approved for use in the United States, only enoxaparin is currently approved for use in unstable angina.
Enoxaparin (Lovenox)
Low-molecular-weight heparin (enoxaparin; Lovenox), which is produced by partial chemical or enzymatic depolymerization of unfractionated heparin, binds to antithrombin III, enhancing its therapeutic effect. The heparin–antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). LMWH differs from unfractionated heparin by having a higher ratio of antifactor Xa to antifactor IIa than does unfractionated heparin. Maximum antifactor Xa and antithrombin activities occur 3-5 hours after administration.
Direct thrombin inhibitors
Class Summary
Direct thrombin inhibitors bind directly to the anion binding site and the catalytic sites of thrombin to produce potent and predictable anticoagulation.
Hirudin (Lepirudin, Refludan)
Hirudin (Lepirudin, Refludan) is the prototype of direct thrombin inhibitors. Hirudin binds directly to the anion binding site and the catalytic sites of thrombin to produce potent and predictable anticoagulation. Currently, hirudin is indicated only in patients who are unable to receive heparin because of heparin-induced thrombocytopenia.
Bivalirudin (Angiomax)
Bivalirudin (Angiomax) is a synthetic analogue of recombinant hirudin. It inhibits thrombin and is used for anticoagulation in unstable angina in patients undergoing PTCA. Potential advantages over conventional heparin therapy include more predictable and precise levels of anticoagulation, activity against clot-bound thrombin, absence of natural inhibitors (eg, platelet factor 4, heparinase), and continued efficacy following clearance from plasma (because of binding to thrombin).
Adenosine diphosphate receptor antagonists
Class Summary
Thienopyridine adenosine 5'-diphosphate (ADP) antagonists approved for antiplatelet activity in the United States include clopidogrel, ticlopidine, prasugrel, and ticagrelor. All but ticagrelor have irreversible antiplatelet activity and take several days to manifest an effect, whereas, ticagrelor is a reversible P2Y12 receptor inhibitor. A potential additive benefit exists when ADP antagonists are used in conjunction with aspirin. These drugs may be considered alternatives to aspirin in patients with aspirin intolerance or who are allergic to aspirin.
Clopidogrel (Plavix)
Clopidogrel (Plavix) inhibits ADP-dependent activation of the glycoprotein IIb/IIIa complex, a necessary step for platelet aggregation. This process results in intense inhibition of platelet function, particularly in combination with aspirin.
Clopidogrel can be considered an alternative to aspirin in patients with aspirin intolerance or who are allergic to aspirin. The CURRENT-OASIS 7 trial suggests that a 7-day double-dose clopidogrel regimen can be considered for patients with acute coronary syndromes, as the efficacy and safety did not differ from that of a high- and low-dose aspirin regimen. However, there is no benefit in the double-dose treatment for patients who are undergoing an early invasive strategy.[90]
Clopidogrel is a class I recommendation for patients when an early noninterventional approach is planned in therapy.[91] When percutaneous coronary intervention (PCI) is planned, clopidogrel is started and continued for at least 1 month and for up to 9 months, if the patient is not at high risk for bleeding.
Clopidogrel is generally preferred over ticlopidine (Ticlid), because it more rapidly inhibits platelets and appears to have a more favorable safety profile.
Clopidogrel has been suggested to be less effective in reducing the rate of cardiovascular events in individuals who carry the loss-of-function CYP2C19 alleles. However, a 2010 study concluded that patients with ACS or atrial fibrillation respond well to clopidogrel, regardless of CYP2C19 loss-of-function carrier status.[92]
Ticlopidine (Ticlid)
Beneficial effects were noted in patients with UA after 2 wk of use in one randomized trial. When compared to controls, ticlopidine use decreased vascular deaths and nonfatal MIs.
Prasugrel (Effient)
Thienopyridine drug that inhibits platelet activation and aggregation through the irreversible binding of its active metabolite to ADP platelet receptors (specifically the P2Y12 receptor). Platelet inhibition is the result of this action.
Indicated to reduce thrombotic cardiovascular (CV) events (including stent thrombosis) with acute coronary syndrome (ACS) that is managed with percutaneous coronary intervention (PCI). Specifically for unstable angina or non – ST-elevation myocardial infarction (NSTEMI) or with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.
Reduces rate of combined endpoint of CV death, nonfatal MI, or nonfatal stroke compared with clopidogrel.
Ticagrelor (Brilinta)
Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. Indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS (unstable angina, non-ST elevation MI, or ST elevation MI).
Clinical trial results showed a reduced rate of combined endpoint of cardiovascular death, MI, or stroke compared to clopidogrel. Difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with PCI, ticagrelor also reduces the rate of stent thrombosis.
The drug is administered with aspirin (loading dose of 325 mg PO once, then 75-100 mg/day). Note that exceeding an aspirin dose of 100 mg/day decreases ticagrelor effectiveness.
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| Characteristic | Risk Score |
| History | |
| Age ≥65 years | 1 |
| At least 3 risk factors for coronary heart disease | 1 |
| Previous coronary stenosis ≥50% | 1 |
| Use of aspirin in previous 7 days | 1 |
| Presentation | |
| At least 2 anginal episodes in the previous 24 hours | 1 |
| ST-segment elevation on admission ECG | 1 |
| Elevated levels of serum biomarkers | 1 |
| Total Score | 0-7 |
| Note: Event rates significantly increased as the TIMI risk score increased in the test cohort in the TIMI IIB study. Rates were 4.7% for a score of 0/1, 8.3% for 2, 13.2% for 3, 19.9% for 4, 26.2% for 5, and 40.9% for 6/7 (P < .001, χ2 test for the trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P < .001). | |
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