Ischemic Heart Disease Pharmacotherapy

• Ischemic Heart Disease pharmacotherapy was presented on April 8, 2025 by James Nawarskas, PharmD, PhC, BCPS

Learning Objectives

• Understand the mechanisms of action of drugs used to treat ischemic heart disease
• Identify common adverse reactions associated with these drugs
• Be able to recommend an appropriate treatment regimen for a patient with ischemic heart disease

Oxygen Supply and Demand

• Oxygen supply depends on arterial pO2, hemoglobin concentration, coronary blood flow/distribution, and coronary microcirculation
• Oxygen demand depends on heart rate, wall force, contractile state, and other minor factors

Platelet Activation

• Platelets, tissue factor, and fibrin are key components in clot formation
• Aspirin, thienopyridines, ticagrelor, eptifibatide, and tirofiban are drugs that affect platelet activity

Aspirin

• Aspirin is a gold standard, inexpensive, and generally effective antiplatelet drug
• A diminished response to aspirin's antiplatelet effect (aspirin resistance) occurs in 5-45% of patients

P2Y12 Receptor Inhibitors

• Clopidogrel (Plavix®) is an irreversible P2Y12 receptor inhibitor with a steady-state IPA of 40-62% and a maximum of ~50%, requiring two-step P450 activation, with an offset of action of 5-7 days; dose is oral, once daily
• Prasugrel (Effient®) is an irreversible P2Y12 receptor inhibitor with a steady-state IPA of ~70% and a maximum of ~80%, requiring one-step P450 activation, with an offset of action of 5-7 days; dose is oral, once daily
• Ticagrelor (Brilinta®) is a reversible P2Y12 receptor inhibitor with a steady-state IPA of 80-90% and a maximum of 88%, not requiring metabolism for effect, with an offset of action of 3-5 days; dose is oral, twice daily

Antiplatelet Drugs

• Clopidogrel (75-325 mg/d, once daily) is indicated for recent MI/stroke and established peripheral arterial disease and has few contraindications, clinical efficacy is +, and bleeding risk is +
• Prasugrel (75-325 mg/d, once daily) is indicated for ACS with PCI and is contrainidcated for prior transient ischemic attack or stroke, clinical efficacy is ++, and bleeding risk is ++
• Ticagrelor (< 100 mg/d, twice daily) is indicated for ACS post-MI and is contrainidcated for prior intracranial hemorrhage/severe hepatic impairment, clinical efficacy is ++, and bleeding risk is ++

Antiplatelet Drug Recommendations

• Aspirin 162-325 mg should be administered ASAP for acute treatment then 81-162 mg indefinitely
• Clopidogrel: 300-600 mg loading dose, then 75 mg once daily
• Prasugrel: 60 mg loading dose, then 5-10 mg once daily
• Ticagrelor: 180 mg loading dose, then 60-90 mg twice daily

Beta-Blockers

• Beta-blockers lower heart rate and cardiac contractility
• Beta-blockers limit myocardial damage and mortality

Beta-Blocker Treatment Algorithm

• Administer beta-blockers for at least a year post-MI
• Give carvedilol, metoprolol succinate, or bisoprolol as soon as heart failure is stabilized and continue indefinitely
• Do not give beta-blockers to patients who have signs of heart failure, risk factors for cardiogenic shock, HR < 50 bpm, heart block, hypotension (SBP < 100 mm Hg), or severe COPD/asthma
• Long-acting oral nitrates can be used to treat or prevent ischemic symptoms
• Verapamil or diltiazem can be used instead of long-acting nitrate

Nitroglycerin

• Nitroglycerin causes venodilation, dilates epicardial vessels, increases blood flow to collateral vessels, and alleviates coronary spasm
• Nitroglycerin is primarily used for symptomatic relief

Nitrate Products

• Intravenous nitroglycerin is used for acute relief of angina and the dose is 10 mcg/min continuous IV infusion up-titrated in 10 mcg/min intervals every 3-5 min as needed, and has a onset of 1-2 minutes
• Sublingual nitroglycerin (Nitrostat) is used for acute relief of angina and the dose is 0.3–0.6 mg prn every 5 min (up to 3 doses) or 0.4-0.8 mg prn q 5 min, up to 0.12 mg over 15 min, and has a onset of 1-3 minutes due to rapid absorption through mucosa
• Oral nitrates (isosorbide dinitrate [ISDN], isosorbide mononitrate [ISMN]) are used for chronic prophylaxis of angina pectoris

Nitrate Prescribing Considerations

• Development of nitrate tolerance is major prescribing consideration
• Headache is a common adverse effect

Nitroglycerin Recommendations

• All patients should be given sublingual nitroglycerin and instructed to take one in response to chest discomfort/pain
• If chest discomfort/pain is unimproved or worsening 5 minutes after 1 sublingual nitroglycerin, the patient or family member/friend should call 911 immediately
• While activating EMS, additional sublingual nitroglycerin (at 5-min intervals x 2) can be taken while lying down or sitting

ACE Inhibitors/ARBs

• ACE inhibitors/ARBs limit post-infarction left ventricular dilatation and hypertrophy
• ACE inhibitors/ARBs decrease progression to CHF, reinfarction, and mortality
• Patients with left ventricular ejection fraction (LVEF) < 40% derive the most benefit
• Begin therapy ASAP

RAAS Inhibitor Treatment Algorithm

• ACE inhibitors should be given and continued indefinitely
• Eplerenone can be added to ACE inhibitors for patients with LVEF < 40%

Calcium Channel Blockers

• Calcium channel blockers reduce vascular resistance, dilate coronary arteries, and reduce heart rate and cardiac contractility
• Calcium channel blockers relieve chest pain

Calcium Channel Blocker Treatment Algorithm

• Non-dihydropyridines may be used to treat or prevent ischemic symptoms
• A dihydropyridine may be used to treat or prevent ischemic symptoms

Statins

• Statins block cholesterol synthesis and reduce circulating concentrations of atherogenic lipid particles
• Statins lower the risk of coronary heart disease, death, recurrent MI, stroke, and the need for coronary revascularization

Ranolazine (Ranexa)

• Ranolazine is the last-line antianginal drug in patients with angina refractory to beta-blockers, nitrates, and calcium channel blockers
• Dosage is 500 mg BID, increasing as needed to 1000 mg BID

SGLT2 Inhibitor & GLP-1 Agonists

• SGLT2 inhibitors reduce CV mortality and incident and worsening heart failure
• GLP-1 agonists primarily reduce atherosclerotic events, such as MI and stroke
• Benefits are currently restricted to those with type 2 diabetes unless heart failure is present
• SGLT2 inhibitors or GLP-1 agonists can be given for CAD or type 2 diabetes if LVEF is less than 40%

Case Questions

• Tachycardia is most likely to occur with nitrate therapy
• Nitroglycerin sublingual is used to treat acute chest pain
• Nitrostat 0.4 mg, one tablet every 10 minutes as needed for chest pain is the most appropriate nitrate regimen
• Blockade of beta receptors does all of the following EXCEPT cause vasodilation
• Nicardipine is preferred for treating ischemic heart disease in a patient already taking a beta-blocker
• Verapamil blocks both Ca and Beta receptors and should be avoided in systolic heart failure
• A patient who develops an increase in serum creatinine, a cough, or angioedema while on ACE inhibitors is best suited for an ARB instead of an ACE inhibitor
• Aspirin + clopidogrel for 12 months is the most appropriate antiplatelet regimen for a 62-year-old male who just received a drug-eluting stent during hospitalization for a non-ST-elevation myocardial infarction and not considered high risk for bleeding
• Sublingual nitroglycerin tablets alone is the best nitrate regimen to recommend for a patient that is about to be discharged from the hospital following coronary stent placement for a non-STEMI that is chest pain-free ever since the stent was placed
• Carvedilol is recommended for treating a patient with a non-STEMI and reduced left ventricular function
• An ACE inhibitor should be recommended (Class I recommendation) as part of chronic therapy in all unstable angina patients except those patients that have peripheral vascular disease
• Isosorbide mononitrate is used for pressure-like CP
• Dulaglutide/Tirzepatide is/are recommended for a patient with CAD, diabetes, and an LVEF of 50%
• Rosuvastatin 20 mg daily for lipid-lowering regimens is most appropriate (i.e. Class I recommendation) for a 66 year old STEMI patient