Coronary Artery Atherosclerosis Medication
- Author: F Brian Boudi, MD; Chief Editor: Yasmine Subhi Ali, MD, MSCI, FACC, FACP more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and mortality and to prevent complications. Prevention and treatment of atherosclerosis requires risk factor control, including the medical treatment of hypertension, diabetes mellitus, and cigarette habituation.
Advances in the understanding of the vascular biology of atherosclerosis raise the possibility of novel therapies that address more directly the various aspects of endothelial dysfunction and the role of endothelial dysfunction in atherogenesis. Potential cellular targets include vascular smooth muscle cells, monocyte/macrophage cell lines, platelets, and endothelial cells. Evidence shows that antiplatelet agents, antioxidant therapies, amino acid supplementation, ACE inhibitors, and angiotensin-receptor blockers may be able to prevent or slow the progression of atherosclerosis.
Combination therapy in the future may allow for the achievement of greater LDL-C lowering, with associated cardiovascular benefit. In one example of such therapy, however, treatment with Vytorin, which combines ezetimibe (decreases small intestinal absorption of cholesterol) with simvastatin, has produced no incremental benefit in cardiovascular morbidity and mortality over and above that demonstrated for simvastatin alone.
Another cholesteryl ester transfer protein inhibitor that raises HDL while reducing LDL is anacetrapib. Patients with coronary heart disease or those who are at high risk for coronary heart disease who were treated with this drug had few adverse side effects and few adverse cardiovascular effects.[72]
Patients who are discharged on antilipid medications that were begun in the hospital tend to stay on the therapy and to derive significant reduction in the recurrent cardiac event rate. The AHA has promulgated its Get With the Guidelines program, which involves an Internet-based checklist of discharge medications to ensure that CAD patients are started on aspirin, beta-blockers, ACE inhibitors, and statins (if needed) in the hospital.[73]
HMG-CoA Reductase Inhibitors
Class Summary
These agents lower LDL-C levels by reducing the production of mevalonic acid from HMG-CoA and by stimulating LDL catabolism. They also lower triglyceride levels and raise serum HDL-C levels, and they have a low incidence of adverse effects, the most common being hepatotoxicity and myopathy. Aspirin and HMG-CoA reductase inhibitors may reduce plaque inflammation.[68]
HMG-CoA reductase inhibitors include the following:
- Atorvastatin (Lipitor)
- Pravastatin (Pravachol)[68, 24, 74]
- Simvastatin (Zocor)[75, 76]
- Rosuvastatin (Crestor)
- Pitavastatin (Livalo)
- Lovastatin (Mevacor, Altocor)[77]
- Fluvastatin (Lescol)
Atorvastatin, pravastatin, simvastatin, and rosuvastatin competitively inhibit HMG-CoA, which catalyzes the rate-limiting step in cholesterol synthesis. One study suggests that the maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Although rosuvastatin resulted in lower LDL cholesterol levels and higher HDL cholesterol levels, a similar degree of regression of percent atheroma value (PAV) was observed in the two groups.[78] Before initiating therapy, place patients on a cholesterol-lowering diet for 3-6 months, and continue diet indefinitely. Holdaas et al suggest the use of rosuvastatin for patients with diabetes mellitus because it may better reduce the risk of fatal and nonfatal cardiac events.[79]
Pitavastatin is indicated for primary or mixed hyperlipidemia. Lovastatin is an adjunct to dietary therapy in reducing serum cholesterol; immediate-release (Mevacor) and extended-release (Altocor) versions are available. Fluvastatin is also used as an adjunct to dietary therapy in decreasing cholesterol levels.
Atorvastatin (Lipitor)
Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.
Pravastatin (Pravachol)
Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.
Simvastatin (Zocor)
Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.
Rosuvastatin (Crestor)
Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.
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.
Lovastatin (Mevacor, Altocor)
Adjunct to dietary therapy in reducing serum cholesterol. Immediate-release (Mevacor) and extended-release (Altocor) are available.
Fluvastatin (Lescol)
Used as an adjunct to dietary therapy in decreasing cholesterol levels.
ACE Inhibitors
Class Summary
Hypertension and atherosclerosis may be intimately linked through their effects on vascular endothelial dysfunction, which are mediated by the renin-angiotensin system (RAS). Angiotensin II (A-II), a potent vasoconstrictor and the principal active peptide of the RAS, can produce structural changes in the vessel wall associated with atherosclerosis. The ACE inhibitors ramipril (Altace) and quinapril (Accupril) prevent conversion of angiotensin I (A-I) to A-II, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. Examples of other commonly used ACE inhibitors are captopril (Capoten), enalapril (Vasotec), and lisinopril (Zestril).
Ramipril (Altace)
Prevents conversion of A-I to A-II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Quinapril (Accupril)
Prevents conversion of A-I to A-II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Captopril (Capoten)
Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
Rapidly absorbed, but bioavailability is significantly reduced with food intake. It achieves a peak concentration in an hour and has a short half-life. The drug is cleared by the kidney.
Impaired renal function requires reduction of dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.
Can be started at low dose and titrated upward as needed and as patient tolerates.
Enalapril (Vasotec)
Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Helps control blood pressure and proteinuria. Decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. Has favorable clinical effect when administered over a long period. Helps prevent potassium loss in distal tubules. Body conserves potassium; thus, less oral potassium supplementation needed.
Lisinopril (Zestril)
Prevents conversion of Angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Calcium Channel Blocker
Class Summary
Calcium channel blockers inhibit calcium ions from entering slow channels, select voltage-sensitive areas, and vascular smooth muscle. The calcium-channel blocker amlodipine (Norvasc) relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery. Because the atherosclerotic plaque is marked by changes in calcium regulation, the potential antiatherosclerotic role for calcium antagonists has piqued interest.
Amlodipine (Norvasc)
Relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery.
Nifedipine (Procardia, Procardia XL, Adalat, Adalat CC, Nifedical XL)
Relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery. Sublingual administration is generally safe, despite theoretical concerns.
Verapamil (Calan, Calan SR, Covera-HS, Verelan)
During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of the vascular smooth muscle and myocardium.
Felodipine (Plendil)
Relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery.
Benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. Can be used during pregnancy if indicated clinically.
Calcium channel blockers potentiate ACE inhibitor effects. Renal protection is not proven, but these agents reduce morbidity and mortality rates in congestive heart failure. Calcium channel blockers are indicated in patients with diastolic dysfunction. Effective as monotherapy in black patients and elderly patients.
Calcium channel blockers potentiate ACE inhibitor effects. Renal protection is not proven, but these agents reduce morbidity and mortality rates in congestive heart failure. Calcium channel blockers are indicated in patients with diastolic dysfunction. Effective as monotherapy in black patients and elderly patients.
Diltiazem (Cardizem, Cardizem LA, Cardizem CD, Tiazac, Dilacor)
During depolarization, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged. The resultant decrease in intracellular calcium inhibits the contractile processes of myocardial smooth muscle cells, resulting in dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.
Decreases conduction velocity in AV node. Also increases refractory period via blockade of calcium influx. This, in turn, stops reentrant phenomenon.
Decreases myocardial oxygen demand by reducing peripheral vascular resistance, reducing heart rate by slowing conduction through SA and AV nodes, and reducing LV inotropy. Slows AV nodal conduction time and prolongs AV nodal refractory period, which may convert SVT or slow the rate in atrial fibrillation. Also has vasodilator activity but may be less potent than other agents. Total peripheral resistance, systemic blood pressure, and afterload are decreased.
Calcium channel blockers provide control of hypertension associated with less impairment of function of the ischemic kidney. Calcium channel blockers may have beneficial long-term effects, but this remains uncertain.
Platelet Aggregation Inhibitors
Class Summary
Platelet aggregate inhibitors may have a positive influence on several hemorrhagic parameters and may exert protection against atherosclerosis through inhibition of platelet function and through changes in the hemorrhagic profile.
Platelet aggregate inhibitors include the following:
- Clopidogrel (Plavix)
- Abciximab (ReoPro)
- Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)
Clopidogrel selectively inhibits ADP binding to platelet receptors and subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex, thereby inhibiting platelet aggregation.
Abciximab is a chimeric human-murine monoclonal antibody approved for use in elective/urgent/emergent PCI. It binds to receptors with high affinity and reduces platelet aggregation by 80% for up to 48 hours following infusion. Abciximab prevents acute cardiac ischemic complications in patients with unstable angina that is unresponsive to conventional therapy.
Aspirin inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2. Aspirin may be used in low doses to inhibit platelet aggregation and to improve complications of venous stases and thrombosis.
Clopidogrel
Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein IIb/IIIa complex, thereby inhibiting platelet aggregation.
Abciximab (ReoPro)
Chimeric human-murine monoclonal antibody approved for use in elective/urgent/emergent percutaneous coronary intervention. Binds to receptor with high affinity and reduces platelet aggregation by 80% for up to 48 h following infusion. Prevents acute cardiac ischemic complications in patients with unstable angina unresponsive to conventional therapy.
Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)
Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.
Polyunsaturated Fatty Acids
Class Summary
Long-chain omega-3 polyunsaturated fatty acids (PUFAs) possess several properties that may positively influence vascular function. These include favorable mediator profiles (nitric oxide, eicosanoids), which influence vascular reactivity, change vascular tone via actions on selective ion channels, and maintain vascular integrity. In addition to direct effects on contractility, omega-3 PUFAs may affect vascular function and the process of atherogenesis via inhibition of vascular SMC proliferation at the gene expression level and modification of expression of inflammatory cytokinesis and adhesion molecules.
Omega-3 polyunsaturated fatty acid (Fish oil)
Possible benefits in the treatment of atherosclerosis include effects on lipoprotein metabolism, hemostatic function, platelet/vessel wall interactions, anti-arrhythmic actions and also inhibition of proliferation of smooth muscle cells and therefore growth of the atherosclerotic plaque. Fish oil feeding has also been found to result in moderate reductions in blood pressure and to modify vascular neuroeffector mechanisms.
Fibric Acid Derivatives
Class Summary
The precise mechanism of action of fibric acid derivatives, which includes fenofibrate (Tricor) and gemfibrozil (Lopid), is complex and incompletely understood. These agents increase the activity of lipoprotein lipase and enhance the catabolism of triglyceride-rich lipoproteins, which is responsible for an increase in the HDL-C fraction. A decrease in hepatic VLDL synthesis and an increase in cholesterol excretion into bile also appear to occur. The fibrates typically reduce triglyceride levels by 20-50% and increase HDL-C levels by 10-15%.
Fenofibrate is used as an adjunct to dietary therapy in treating hyperlipidemias (including types IV and V) associated with hypertriglyceridemia. It has not been proven to be of use in the prevention of CAD.
Gemfibrozil is used as an adjunct to dietary therapy in adult patients with type IV and V hyperlipidemias who present at risk for pancreatitis. It is also employed in adjunctive therapy in coronary heart disease prevention in patients with type IIb hyperlipidemia (low HDL, elevated LDL and triglycerides) who do not respond to other agents or to diet modifications.
The effect on LDL-C is variable. levels may be expected to decrease by 10-15%. In patients with marked hypertriglyceridemia, LDL-C levels may increase, which likely reflects the ability of the LDL receptor to clear the increased LDL generated by increased VLDL catabolism. Fibrate therapy may also be responsible for a decrease in the clotting ability of platelets and fibrinogen levels, which may account for some of the reported clinical benefits.
Fenofibrate (Tricor)
Adjunct to dietary therapy in treating hyperlipidemias associated with hypertriglyceridemia, including type IV and type V. Not proven to be of use in prevention of coronary artery disease.
Gemfibrozil (Lopid)
Adjunct to dietary therapy in adult patients with type IV and V hyperlipidemias presenting at risk for pancreatitis. Adjunctive therapy in coronary heart disease prevention in patients with type IIb hyperlipidemia (low HDL, elevated LDL and triglycerides) not responding to other agents or diet modifications.
Adjunct to dietary therapy in adult patients with type IV and V hyperlipidemias presenting at risk for pancreatitis. Adjunctive therapy in coronary heart disease prevention in patients with type IIb hyperlipidemia (low HDL, elevated LDL and triglycerides) not responding to other agents or diet modifications.
Bile Acid Sequestrants
Class Summary
The bile acid sequestrants block enterohepatic circulation of bile acids and increase the fecal loss of cholesterol. This results in a decrease in intrahepatic levels of cholesterol. The liver compensates by up-regulating hepatocyte LDL-receptor activity. The net effect is a 10-25% reduction in LDL-C, but no consistent effect on triglycerides or HDL-C exists. Bile acid sequestrants include cholestyramine (Questran, LoCholest, Prevalite) and colestipol (Colestid).
Cholestyramine can be used as an adjunct in primary hypercholesterolemia. It forms a nonabsorbable complex with bile acids in the intestine, which in turn inhibits enterohepatic reuptake of intestinal bile salts.
Colestipol forms a soluble complex after binding to bile acid, increasing fecal loss of bile acid–bound LDL-C.
Colestipol (Colestid)
Forms a soluble complex after binding to bile acid, increasing fecal loss of bile acid-bound LDL cholesterol.
Cholestyramine (Questran, LoCholest, Prevalite)
May use as adjunct in primary hypercholesterolemia. Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.
May use as adjunct in primary hypercholesterolemia.
Antioxidants
Class Summary
Protect polyunsaturated fatty acids in membranes from attack by free radicals and protect red blood cells against hemolysis. Antioxidants have beneficial effects on cell functions and protective properties that are pivotal in atherogenesis and cardiovascular disease. Antioxidants may inhibit platelet aggregation and proinflammatory activity of monocytes.
Vitamin E (Vita-Plus E, Softgels, Aquasol E)
Protects polyunsaturated fatty acids in membranes from attack by free radicals.
Nicotinic Acid Derivatives
Class Summary
The nicotinic acid derivative niacin (Niaspan, Niacor, Slo-Niacin), or vitamin B-3, inhibits the hepatic secretion of VLDL-C. Used in tissue respiration, lipid metabolism, and glycogenolysis, niacin is effective in most categories of hyperlipidemia. It has been demonstrated to lower LDL-C and triglyceride levels by 32% and 20-50%, respectively, and to raise the HDL-C level by 43%. Niacin also lowers lipoprotein(a) levels; this may be of some clinical importance, because lipoprotein(a) levels have been associated with coronary heart disease in numerous epidemiologic studies. The clinical benefit of lowering lipoprotein(a) levels has not been determined.
The extended-release formulation of niacin may reduce flushing, an unpleasant adverse effect that causes 30-40% of patients to discontinue niacin therapy.
Niacin (Niaspan, Niacor, Slo-Niacin)
Used in tissue respiration, lipid metabolism, and glycogenolysis. Available in immediate- and extended-release formulations. Extended-release formulation may reduce flushing, an unpleasant adverse effect that causes 30-40% of patients to discontinue therapy.
Antianginal Agent
Class Summary
Ranolazine is a novel antianginal agent believed to relieve ischemia by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current of the cardiac action potential.
Ranolazine (Ranexa)
Cardioselective anti-ischemic agent (piperazine derivative) that partially inhibits fatty acid oxidation. Also inhibits late sodium current into myocardial cells and prolongs QTc interval. Indicated for chronic angina unresponsive to other antianginal treatments. Used in combination with amlodipine, beta-blockers, or nitrates. Unlike beta-blockers, calcium channel blockers, and nitrates, does not reduce blood pressure or heart rate. Effect on angina rate or exercise tolerance appears to be smaller in women than in men. Absorption is highly variable but unaffected by food.
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