Unstable Angina Medication

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, among others.

Medications that have compelling evidence for reducing short- or long-term adverse events are as follows:

• Aspirin
• Clopidogrel
• Lipid-lowering agents (statins)
• Glycoprotein IIb/IIIa antagonists
• Beta-adrenergic blocking agents
• ACE inhibitors

Class Summary

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

Aspirin (Anacin, Bayer Buffered Aspirin, Ecotrin)

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

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to platelet receptors and subsequent ADP-mediated activation of glycoprotein llb/llla complex, thereby inhibiting platelet aggregation. This agent is used as an alternative to aspirin or in addition to aspirin after coronary stenting.^{[13, 24]}

Class Summary

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 LDL, total-C, and triglycerides and they increase HDL levels. Examples of statins are atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol), and pitavastatin (Livalo).

Simvastatin (Zocor)

Inhibits HMG-CoA reductase, which, in turn, inhibits cholesterol synthesis and increases cholesterol metabolism. Used to decrease increased cholesterol 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 active metabolites is longer than that of all the other statins (ie, approximately 48 h, compared with 3-4 h).

Pitavastatin (Livalo)

HMG-CoA reductase inhibitor (statin) indicated for primary or mixed hyperlipidemia. In clinical trials, 2 mg/d reduced total cholesterol and LDL cholesterol similar to atorvastatin 10 mg/d and simvastatin 20 mg/d.

Pravastatin (Pravachol)

Competitively inhibits HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol synthesis.

Class Summary

Glycoprotein IIb/IIIa receptor antagonists reversibly prevent fibrinogen, von Willebrand factor, 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 the GP IIb/IIIa receptor; it reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor, in this way inhibiting platelet aggregation. The drug effects persist over the duration of maintenance infusion and are reversed after the infusion ends. Tirofiban has been approved by the FDA for use in combination with heparin for patients with ACS, patients who are being managed medically, and patients who are undergoing PCI.

Eptifibatide (Integrilin)

Eptifibatide is a cyclic heptapeptide antagonist of the platelet GP IIb/IIIa receptor; its effects are the same as those for tirofiban. It 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)

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

Class Summary

These agents limit heart rate, reduce blood pressure, and have antiarrhythmic properties; they 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. Examples of beta-blockers are metoprolol (Lopressor, Toprol XL), esmolol (Brevibloc), propranolol (Inderal, Inderal LA), nadolol (Corgard), and atenolol (Tenormin).

Atenolol (Tenormin)

Selectively blocks beta1-receptors with little or no affect on beta2 types. Beta-adrenergic blocking agents affect blood pressure via multiple mechanisms. Actions include negative chronotropic effect that decreases heart rate at rest and after exercise, negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure.

Metoprolol (Lopressor, Toprol XL)

Selective beta-1 adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.

Esmolol (Brevibloc)

Esmolol has been shown to reduce episodes of chest pain and clinical cardiac events compared with placebo. The very short half-life (8 min) of this agent allows a large degree of dosing flexibility, such that cardiovascular benefits are comparable to PO propranolol, yet adverse effects can be managed promptly. It 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).

Propranolol (Inderal)

Propranolol is a nonselective beta-blocker that is lipophilic (penetrates the central nervous system). Although it is generally a short-acting agent, long-acting preparations of the drug are also available.

Nadolol (Corgard)

This agent competitively blocks beta-1 and beta-2 receptors. It does not exhibit membrane-stabilizing activity or intrinsic sympathomimetic activity.

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; tissue factor VIIa). It prevents clot reaccumulation after endogenous fibrinolysis. When unfractionated heparin is used, the aPTT should not be checked until 6 hours after the initial heparin bolus.

Class Summary

Low molecular weight heparin (LMWH) is an anticoagulation treatment 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. LMWH is prepared by selectively treating UFH to isolate the low-molecular-weight (< 9000 Da) 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)

Only LMWH now approved by the FDA for the treatment of and prophylaxis for deep venous thrombosis (DVT) 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 unfractionated heparin. Except in overdoses, checking PT or aPTT is not useful because aPTT does not correlate with the anticoagulant effect of fractionated LMWH.

Dalteparin (Fragmin)

Dalteparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the 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.

Class Summary

Direct thrombin inhibitors, such as hirudin, lepirudin (recombinant hirudin), and bivalirudin, are potential alternatives to heparin. 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 heparin-induced thrombocytopenia.

Bivalirudin (Angiomax)

Bivalirudin is a synthetic analogue of recombinant hirudin. It is used for anticoagulation in patients with unstable angina undergoing PTCA. With provisional use of GP IIb/IIIa inhibitor indicated for use as anticoagulant in patients undergoing PCI. 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).

Lepirudin (Refludan)

Lepirudin is recombinant hirudin derived from yeast cells and 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 heparin-induced thrombocytopenia and associated thrombotic disease.

Desirudin (Iprivask)

Selective inhibitor of free circulating and clot-bound human thrombin, with protein structures similar to naturally occurring hirudin (an anticoagulant present in medicinal leeches). Prolongs thrombin-dependent coagulation assays (eg, aPTT, thrombin time [TT]).

Argatroban

Used as an anticoagulant for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT). Inhibits fibrin formation, platelet aggregation, and activation of coagulation factors V, VIII, XIII, and protein C.

Class Summary

These agents relieve chest discomfort by improving myocardial oxygen supply, which in turn dilates epicardial and collateral vessels, 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 myocardial infarction but may reduce mortality only slightly. Nitroglycerin can be administered sublingually by tablet or spray, topically, or by IV. In acute myocardial infarction, 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, SL, PO, 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 transient inhibition of platelet aggregation, increase in coronary collateral blood flow, and a favorable redistribution of regional flow. Of note, induction of heparin resistance has been reported.

Class Summary

These agents are competitive inhibitors of angiotensin-converting enzyme (ACE). They reduce angiotensin II levels, thus decreasing aldosterone secretion. ACE inhibitors are of particular benefit in patients with large anterior infarctions, especially 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. It helps 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. It helps 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.