Unstable Angina Medication

Updated: Nov 22, 2015
  • Author: Walter Tan, MD, MS; Chief Editor: Eric H Yang, MD  more...
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Medication

Medication Summary

Medications that provide symptomatic relief but have not been found to have an effect on long-term major events include nitrates, diltiazem or verapamil, and heparin. Medications that have been convincingly shown to reduce short- or long-term adverse events are as follows:

  • Aspirin
  • P2Y12 inhibitors
  • Lipid-lowering agents (statins)
  • Glycoprotein (GP) IIb/IIIa antagonists
  • Beta-adrenergic blocking agents
  • Angiotensin-converting enzyme (ACE) inhibitors
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Antiplatelet agents

Class Summary

Antiplatelet agents prevent the formation of thrombi associated with myocardial infarction (MI) and inhibit platelet function by blocking aggregation. Antiplatelet therapy has been shown to reduce mortality by reducing the risk of fatal MIs, fatal strokes, and vascular death.

Aspirin (Anacin, Bayer Buffered Aspirin, Ecotrin)

Aspirin prevents the formation of thrombi associated with MI and inhibits platelet function by blocking aggregation. Antiplatelet therapy has been shown to reduce mortality by reducing the risk of fatal MIs, fatal strokes, and vascular death.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to platelet receptors and subsequent ADP-mediated activation of GP llb/llla complex, thereby inhibiting platelet aggregation. This agent is used as an alternative to aspirin or in addition to aspirin after coronary stenting.

Ticagrelor (Brilinta)

Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. This agent is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS)—that is, unstable angina, non-ST elevation MI (NSTEMI), or ST-elevation MI (STEMI). It also reduces the rate of stent thrombosis in patients who have undergone stent placement for treatment of ACS, and is indicated in patients with a history of MI more than 1 year previously. Patients can be transitioned from clopidogrel to ticagrelor without interruption of the antiplatelet effect.

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Lipid-Lowering Agents, Statins

Class Summary

Lipid lowering agents, specifically the HMG-CoA reductase inhibitors, also known as the statins, are used to treat hypercholesterolemia; they are highly efficacious and very well tolerated. The statins are highly effective in reducing low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides, and they also increase high-density lipoprotein cholesterol (HDL-C) levels.

Simvastatin (Zocor)

Simvastatin inhibits HMG-CoA reductase, and this, in turn, inhibits cholesterol synthesis and increases cholesterol metabolism. This agent is used to decrease increased cholesterol levels associated with nephrotic syndrome.

Atorvastatin (Lipitor)

Atorvastatin can provide up to 60% reduction in LDL-C. It inhibits HMG-CoA reductase, thereby inhibiting cholesterol synthesis and increasing cholesterol metabolism. The half-life of atorvastatin and its active metabolites is longer than those of all the other statins (ie, approximately 48 hours, as opposed to 3-4 hours). Atorvastatin is one of the most extensively studied statins, and many long term evidence-based medicine trials support its benefits.

Pitavastatin (Livalo)

Pitavastatin is an HMG-CoA reductase inhibitor (statin) indicated for primary or mixed hyperlipidemia. In clinical trials, pitavastatin 2 mg/day achieved reductions in total cholesterol and LDL-C similar to those seen with atorvastatin 10 mg/day and simvastatin 20 mg/day.

Pravastatin (Pravachol)

Pravastatin competitively inhibits HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol synthesis. This agent is a good alternative if other statins are not tolerated.

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Antiplatelet Agent, Cardiovascular

Class Summary

Specific cardiovascular antiplatelet agents work via GP IIb/IIIa receptor antagonists to reversibly prevent fibrinogen, von Willebrand factor (vWF), and other adhesion ligands from binding to the GP IIb/IIIa receptor, thereby inhibiting platelet aggregation. Up to 80,000 copies of these integrins on the platelet cell surface serve as ligands for fibrinogen cross-linkage, the final common pathway for platelet aggregation and thrombus formation, even under arterial shear stress conditions.

Tirofiban (Aggrastat)

Tirofiban is a nonpeptide antagonist of the platelet GP IIb/IIIa receptor; it reversibly prevents vWF, fibrinogen, and other adhesion ligands from binding to the receptor, thus inhibiting platelet aggregation. Effects persist over the duration of maintenance infusion and are reversed after the infusion ends. Tirofiban is approved by the US Food and Drug Administration (FDA) to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

Eptifibatide (Integrilin)

Eptifibatide is a cyclic heptapeptide antagonist of the platelet GP IIb/IIIa receptor; its effects are the same as those of tirofiban. This agent has been approved by the FDA for use in combination with heparin for patients with ACS, patients who are being managed medically, and patients undergoing PCI.

Abciximab (ReoPro)

Abciximab is a chimeric human-murine monoclonal antibody approved for use in elective, urgent, and emergency PCI. Abciximab binds to receptors with high affinity and reduces platelet aggregation by 80% for up to 48 hours following infusion.

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Beta-Blockers, Beta-1 Selective

Class Summary

Selective beta1-adrenergic blocking agents limit heart rate, reduce blood pressure, and exert antiarrhythmic effects by targeting beta1 receptor sites. All beta-adrenergic blocking agents thus decrease myocardial oxygen demand and oppose the effects of elevated catecholamines. Infrequent situations in which beta-blocker therapy should be avoided in patients with unstable angina include nonischemic exacerbation of heart failure, cocaine-induced coronary vasoconstriction, and vasospastic angina.

Atenolol (Tenormin)

Atenolol (Tenormin)

Atenolol blocks beta1 receptors but has little or no effect on beta2 types. Beta blockers affect blood pressure via multiple mechanisms, including a negative chronotropic effect that decreases heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the central nervous system (CNS), and suppression of renin release. Atenolol improves and preserves hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure.

Metoprolol (Lopressor, Toprol XL)

Metoprolol is a selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions. During intravenous (IV) administration, carefully monitor blood pressure, heart rate, and the electrocardiogram (ECG).

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Beta-Blockers, Beta-1 Selective; Antidysrhythmics, II

Class Summary

Esmolol acts as a beta-adrenergic blocking agent to limit heart rate and reduces blood pressure by selectively targeting beta1 receptor sites; this drug also has class II antiarrhythmic properties. All beta-adrenergic blocking agents decrease myocardial oxygen demand and oppose the effects of elevated catecholamines. Infrequent situations in which beta-blocker therapy should be avoided in patients with unstable angina include nonischemic exacerbation of heart failure, cocaine-induced coronary vasoconstriction, and vasospastic angina.

Esmolol (Brevibloc)

Esmolol has been shown to reduce episodes of chest pain and clinical cardiac events. Its very short half-life (8 minutes) allows a large degree of dosing flexibility, so that its cardiovascular benefits are comparable to those of oral propranolol, yet its adverse effects can be managed promptly. Esmolol is particularly useful for patients at risk for complications with beta blockade (eg, reactive airway disease or chronic obstructive pulmonary disease [COPD], severe bradycardia, or poor left ventricular function).

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Beta-Blockers, Nonselective

Class Summary

Nadolol is a nonselective beta-adrenergic blocking agent that limits heart rate, reduces blood pressure, and have antiarrhythmic properties. All beta-adrenergic blocking agents thus decrease myocardial oxygen demand and oppose the effects of elevated catecholamines. Infrequent situations in which beta-blocker therapy should be avoided in patients with unstable angina include nonischemic exacerbation of heart failure, cocaine-induced coronary vasoconstriction, and vasospastic angina.

Nadolol (Corgard)

Nadolol competitively blocks beta1 and beta2 receptors. It does not exhibit membrane-stabilizing activity or intrinsic sympathomimetic activity.

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Beta-Blockers, Nonselective; Antidysrhythmics, II

Class Summary

Propranolol is a beta blocker that limits heart rate and reduces blood pressure by nonselectively targeting beta receptor sites; it also has class II antiarrhythmic properties. All beta-adrenergic blocking agents thus decrease myocardial oxygen demand and oppose the effects of elevated catecholamines. Infrequent situations in which beta-blocker therapy should be avoided in patients with unstable angina include nonischemic exacerbation of heart failure, cocaine-induced coronary vasoconstriction, and vasospastic angina.

Propranolol (Inderal)

Propranolol is a nonselective beta blocker that is lipophilic (ie, penetrates the CNS). Although it is generally a short-acting agent, long-acting preparations are also available.

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Anticoagulant

Class Summary

Thrombin, the end product of the coagulation mechanism, initiates transformation of fibrinogen to a fibrin clot and activates platelets. Its antagonist, antithrombin III, is the major endogenous inhibitor of the coagulation cascade and is the essential cofactor for heparin.

Heparin

Heparin catalyzes the effect of antithrombin III on coagulative proteinases (eg, factors II, XII, XI, IX, and X, along with tissue factor VIIa). It prevents clot reaccumulation after endogenous fibrinolysis. When unfractionated heparin (UFH) is used, the activated partial thromboplastin time (aPTT) should not be checked until 6 hours after the initial heparin bolus.

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Low Molecular Weight Heparins

Class Summary

Low-molecular-weight heparin (LMWH) represents an anticoagulation option for unstable angina. The many potential benefits of using LMWH include lower rates of bleeding, cost savings, and reduced incidence of heparin-induced thrombocytopenia (HIT). LMWH is prepared by selectively treating UFH to isolate the low-molecular-weight (< 9 kDa) fragments. Its activity is measured in units of factor X inactivation; monitoring of aPTT is not required, and the dose is weight-adjusted.

Enoxaparin (Lovenox)

Enoxaparin (Lovenox)

Enoxaparin is the only LMWH now approved by the FDA for treatment of and prophylaxis for deep venous thrombosis and pulmonary embolism. LMWH has been widely used in pregnancy, although clinical trials are not yet available to demonstrate that it is as safe as UFH. Except in overdoses, checking the prothrombin time (PT) or aPTT is not useful, because aPTT does not correlate with the anticoagulant effect of fractionated LMWH.

Dalteparin (Fragmin)

Dalteparin enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases inhibition of factor Xa. Except in overdoses, checking PT or aPTT is not useful, because aPTT does not correlate with the anticoagulant effect of fractionated LMWH. The average duration of treatment is 7-14 days.

Tinzaparin (Innohep)

Tinzaparin enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases inhibition of factor Xa. Average duration of treatment is 7-14 days.

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Thrombin inhibitors

Class Summary

Direct thrombin inhibitors, such as hirudin, lepirudin (recombinant hirudin), and bivalirudin, are potential alternatives to heparin. Their advantages over heparin are efficacy against clot-bound thrombin, resistance to inactivation by platelet factor 4 and thrombospondin, and nondependence on antithrombin III pathways. Although direct thrombin inhibitors should not be routinely used in the treatment of unstable angina, they may be of clinical benefit in special circumstances, such as HIT.

Bivalirudin (Angiomax)

Bivalirudin is a synthetic analogue of recombinant hirudin. It is used for anticoagulation in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA).

With provisional use of an GP IIb/IIIa inhibitor, bivalirudin is indicated for use as an anticoagulant in patients undergoing PCI. Its 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 and heparinase), and continued efficacy after clearance from plasma (because of binding to thrombin).

Lepirudin (Refludan)

Lepirudin is recombinant hirudin derived from yeast cells; it is a highly specific direct inhibitor of thrombin. Natural hirudin is produced in trace amounts as a family of highly homologous isopolypeptides by the leech Hirudo medicinalis. Biosynthetic lepirudin is identical to natural hirudin except for the substitution of leucine for isoleucine at the N-terminal end of the molecule and the absence of a sulfate group on the tyrosine at position 63. Lepirudin has been approved by the FDA for use in patients with HIT and associated thrombotic disease.

Desirudin (Iprivask)

Desirudin is a selective inhibitor of free circulating and clot-bound human thrombin, with protein structures similar to those of naturally occurring hirudin (an anticoagulant present in medicinal leeches). It prolongs thrombin-dependent coagulation assays (eg, activated partial thromboplastin time [aPTT] and thrombin time [TT]).

Argatroban

Argatroban is used as an anticoagulant for prophylaxis or treatment of thrombosis in HIT. This agent inhibits fibrin formation, platelet aggregation, and activation of coagulation factors V, VIII, and XIII, as well as protein C.

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Nitrates, Angina

Class Summary

Nitrates are vasodilators that relieve chest discomfort (angina) by improving myocardial oxygen supply, thereby, in turn, dilating epicardial and collateral vessels and thus improving blood supply to the ischemic myocardium. Vasodilators oppose coronary artery spasm, which augments coronary blood flow and reduces cardiac work by decreasing preload and afterload.

These drugs are effective in the management of symptoms in acute MI but may reduce mortality only slightly. Nitroglycerin can be administered sublingually by tablet or spray, topically, or intravenously (IV). In acute MI, topical administration is a less desirable route because of unpredictable absorption and the onset of clinical effects.

Nitroglycerin IV

Nitroglycerin causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. Whether administered topically, sublingually, orally, or IV, nitrates ameliorate several pathways of unstable angina and reduce the incidence of symptomatic ischemia. Nitrates lower systemic arterial pressure and decrease venous return to the heart, both of which reduce myocardial wall stress. Similarly, nitrates are excellent coronary vasodilators.

Other possible beneficial effects include a transient inhibition of platelet aggregation, an increase in coronary collateral blood flow, and a favorable redistribution of regional flow. Notably, induction of heparin resistance has been reported.

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ACE Inhibitors

Class Summary

ACE inhibitors reduce angiotensin II levels, thus decreasing aldosterone secretion. They are of particular benefit in patients with large anterior infarctions, especially those with compromised left ventricular function (eg, from STEMI) but without hypotension. The benefit in patients with unstable angina is less clear. Currently, ACE inhibitors are recommended in patients with left ventricular dysfunction or congestive heart failure, diabetes, and hypertension.

Captopril (Capoten)

Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Lisinopril (Zestril)

Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Enalapril (Vasotec)

Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. This agent helps to control blood pressure and proteinuria.

Enalapril decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. It has a favorable clinical effect when administered over a long period. Enalapril helps to prevent potassium loss in distal tubules. The body conserves potassium; thus, less oral potassium supplementation is needed.

Ramipril (Altace)

Ramipril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

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