IschemicHD_RxPrep Book 2022_11-7-23.pdf

CHAPTER 29 ISCHEMIC HEART DISEASE BACKGROUND Angina is chest pain, pressure, tightness or discomfort, usually caused by ischemia of the heart muscle or spasm of the coronary arteries. The chest pain is described as "squeezing," "grip-like," "heavy" or "suffocating," and typically does not vary with...

CHAPTER 29 ISCHEMIC HEART DISEASE BACKGROUND Angina is chest pain, pressure, tightness or discomfort, usually caused by ischemia of the heart muscle or spasm of the coronary arteries. The chest pain is described as "squeezing," "grip-like," "heavy" or "suffocating," and typically does not vary with position or respiration. Stable angina, also known as stable ischemic heart disease (SIHD}, is associated with predictable chest pain, often brought on by exertion or emotional stress and relieved within minutes by rest or with nitroglycerin. Unstable angina (UA) is a type of acute coronru·y syndrome (ACS); this is a medical emergency where the chest pain nitroglycerin or rest (see Acute Coronary Syndromes chapter} . The classic symptoms of SIHD may not be present in women, elderly patients or those with diabetes; this can lead to misdiagnosis (e.g., GERD) or a delay in treatment. When chest pain is caused by vasospasm of the coronary arteries, it is called Prinzmetal's (variant or vasospastic} angina. This type of angina can occur at rest and can be caused by illicit drug use, particularly cocaine. PATHOPHYSIOLOGY Chest pain occurs when there is an imbalance between myocardial oxygen demand (workload) and supply (blood flow}. In SIHD, myocardial oxygen supply is often decreased due to plaque build up (atherosclerosis) within the inner walls of the coronary arteries. This is known as coronary artery disease (CAD}; it causes narrowing of the arteries and reduced blood flow to the heaL't. Myocardial oxygen demand increases when the heart is working harder due to an increased heart rate, contractility or left ventricular wall tension [caused by increased preload (volume of blood returning to the heart} and/or afterload (systemic vascular resistance, or SVR)]. 458 Rx PREP 20 2 2 CO UR SE BOO K I RxPREP ©202 1 , © 20 22 DIAGNOSIS DRUG TREATMENT The risk factors for SIHD are similar to other types of heart disease, vascular disease and stroke, and include hypertension, smoking, dyslipidemia, diabetes, obesity and physical inactivity. To assess the likelihood of CAD and diagnose SIHD, a cardiac sti·ess test is performed. The treatment goals for SIHD are to improve function (by eliminating chest pain), prevent future cardiovascular events (e.g., Ml, heart failure) and reduce the risk of cardiovascular death. An antiplatelet and an antianginal drug regimen are used together. Antiplatelet treatment prevents platelets from sticking together and forming a clot that can block an artery and reduce blood flow to the heart. Aspirin is the recommended antiplatelet; clopidogrel (Plavix) is used when there is an allergy or other contraindication to aspirin. The cardiac stress test increases myocardial oxygen demand with either exercise (e.g., walking on a treadmill or pedaling a stationary exercise bicycle) or intravenous medications [adenosine, dipyridamole, dobu tamine or regadenoson (Lexiscan)] . As myocardial oxygen demand increases, the patient is monitored for the development of symptoms (e.g., chest pain, dyspnea, lightheadedness), changes in heart rate and blood pressure, transient rhythm disturbances or ST segment abnormalities on an ECG. When the diagnosis of SIHD is certain, coronary angiography can be performed to assess the extent of atherosclerosis and need for revascularization. EVALUATION OF SIHD History and physical CBC, CK-MB, troponins (I orT), aPTT, PT/INR, lipid panel, glucose ECG (at rest and during chest pain) Cardiac stress test/stress imaging Cardiac catheterization/angiography NON-DRUG TREATMENT Patients should be encouraged to follow a heart healthy diet (e.g., saturated fats< 7% and trans fats< 1% of total calories, adequate intake of fresh fruits and vegetables, low-fat dairy products), maintain a BMI of 18.5 - 24.9 kg/ m2 , and maintain a waist circumference < 35 inches in females and< 40 inches in males. Patients should engage in 30 - 60 minutes of moderateintensity aerobic activity 5 - 7 days per week, supplemented by an increase in daily lifestyle activities (e.g., walking breaks at work, gardening). Medically supervised programs, such as cardiac rehabilitation, are encouraged for at-risk patients at first diagnosis. Patients who smoke should quit, and secondhand smoke should be avoided. Alcohol intake should be limited to 1 drink/day (4 oz wine, 12 oz beer or 1 oz of spirits) for women and 1- 2 drinks/day for men. The combination of aspirin and clopidogrel is only beneficial in SIHD when there is a history of stent placement or recent CABG (see Dual Antiplatelet Therapy section on next page). Low-dose rivaroxaban (Xarelto) in combination with aspirin is FDA-approved to reduce the risk of cardiovascular events in patients with CAD or peripheral artery disease (PAD) . Antianginal treatment decreases myocardial oxygen demand or increases myocardial oxygen supply (see Antianginal Treatment table). Beta-blockers are first line; calcium channel blockers (CCBs) , both dihydropyridine (DHP) and non-dihydropyridine (non-DHP), or long-acting nitrates should be used when beta-blockers are contraindicated or when additional symptomatic relief is needed. Ranolazine can be used as a substitute for, or in addition to, betablockers. Short-acting nitroglycerin, as a sublingual (SL) tablet, powder or translingual (TL) spray, is recommended for immediate relief of angina in all patients. SIHD is one of the atherosclerotic cardiovascular diseases (ASCVD) . Patients should be treated with a high-intensity statin (see Dyslipidemia chapter) . Hypertension, heart failure and diabetes should be aggressively managed with guideline-recommended treatments, including the use of an ACE lnMbi tor or ARB to manage hypertension in patients with SIHD and diabetes. An annual influenza vaccine is recommended; pneumococcal vaccines should be administered per ACIP recommendations (see Immunizations chapter). A- Anti platelet and antianginal drugs B - Blood pressure and beta-blockers C- Cholesterol (statins) and cigarettes (cessation) D - Diet and diabetes ~ - Exercise and education 459 29 I ISCHEMIC HE A RT D ISEASE ANTIPLATELET DRUGS Aspirin irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in deo•eased prostaglandin (PG) and thromboxane A2 (TXA2) production. TXA2 is a potent vasoconstrictor and inducer of platelet aggregation. Clopidogrel is a prodrug that irreversibly inhibits .P2Yl2 ADP-mediated platelet activation and aggregation. Refer to the Acute Coronary Syndromes chapter for an image depicting anti platelet drug mechanisms of action. DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING Aspirin (Bayer, Bufferln, Ecotrln, Ascriptin, 75-162 mg daily CONTRAINDICATIONS NSAID or salicylate allergy; children and teenagers with viral infection due to the risk of Reye's syndrome (symptoms include somnolence, N/V, confusion); rhinitis, nasal polyps or asthma (due to risk of urticaria, angioedema or bronchospasm) Durlaza, others) + omeprazole (Yosprala) OTC: tablet, chewable tablet, enteric-coated tablet, suppository 70-100 mg daily when used in combination with rivaroxaban 2.5 mg BID (see Notes) Rx: ER capsule (Durlaza), delayed-release tablet WARNINGS Bleeding [including GI bleed/ulceration, i risk with heavy alcohol use or use with other drugs with bleeding risk (e.g., NSAIDs, anticoagulants, other antiplatelets)], tinnitus (salicylate overdose) SIDE EFFECTS Dyspepsia, heartburn, bleeding, nausea (Yasprala) MONITORING Symptoms of bleeding, bruising See Pain chapter for more information on aspirin products NOTES Used indefinitely in SIHD (linless contraindicated); .J, incidence of Ml, CV events and death Used with low-dose rivaroxaban to reduce the risk of major cardiovascular events (e.g., Ml, stroke) Non-enteric coated , chewable aspirin is preferred in ACS; if only en terlc-coated (EC) aspirin is available, it should be chewed (325 mg) Durlaza and Yosprala should not be used when rapid onset is needed (e.g., ACS, pre-PCI) To .J, nausea, use EC or buffered product or take with food PPls may be used to protect the gut with chronic NSAID use; consider the risks from chronic PPI use ( bone density, infection risk) Yosprala is indicated for those at risk of developing aspirin-associated gastric ulcers Clopidogrel (Plavlx} 75 mg daily Tablet Indicated for ACS (in combination with aspirin), or in patients with recent Ml, stroke or PAD BOXED WARNING Clopidogrel is a prodrug. Effectiveness depends on the conversion to an active metabolite, mainly by CYP450 2C19. Poor metabolizers of CYP2C19 exhibit higher cardiovascular events than patients with normal CYP2C19 function. Tests to check CYP2C19 genotype can be used as an aid in determining a therapeutic strategy. Consider alternative treatments in patients identified as CYP2C19 poor metabolizers. See the Pharmacogenomics chapter. CONTRAINDICATIONS Active serious bleeding (e.g., GI bleed, intracranial hemorrhage) WARNINGS Bleeding risk, stop 5 days prior to elective surgery, do not use w ith omeprazole or esomeprazole (see Drug Interactions section), premature discontinuation (i risk of thrombosis), thrombotic thrombocytopenic purpura (TTP) SIDE EFFECTS Generally well tolerated, unless bleeding occurs MONITORING Symptoms of bleeding, Hgb/Hct as necessary NOTES Used in SIHD when there is a contraindication to aspirin; can be used in combination with aspirin (see Dual Anti platelet Therapy section) Dual Antiplatelet Therapy SIHD is usually treated with a single antiplatelet drug (aspirin or clopidogrel). Dual antiplatelet t herapy (DAPT) with aspirin and clopidogrel is reserved for those who have had placement of a bare metal stent (DAPT for at least one month), a drug-eluting stent (DAPT for at least six months) or post-CABG (DAPT for 12 months). Clopidogrel is the only P2Y12 inhibitor recommended in SIHD. Aspirin is dosed at 81 mg daily in DAPT regimens and is continued indefinitely at 75 - 162 mg daily after the course of DAFT is complete. Refer to the Acute Coronary Syndromes chapter for a discussion of DAFT in ACS. 460 RxPREP 2022 COURS E BOOK I RxPREP ©2021, ©2022 Antiplatelet Drug Interactions Most drug interactions are due to additive effects with other drugs that can't bleeding risk (e.g., anticoagulants, NSAIDs, SSRis, SNRis, some herbals). See the Drug Interactions chapter. Aspirin: use caution in combination with other ototoxic drugs (see the Drug Interactions chapter). Clopidogrel: avoid in combination with CYP2Cl9 inhibitors omeprazole and esomeprazole (other PPls interact less) and use caution with other CYP2C19 inhibitors. ANTIANGINAL TREATMENT DRUG MECHANISM OF CLINICAL BENEFIT CLINICAL NOTES Beta-Blockers Reduce myocardial oxygen demand: -l- HR, -l- contractility and -l- left ventricular ~ension Start low, go slow; titrate to resting HR of SS-60 BPM; avoid abrupt withdrawal 1st line in SIHD See the Hypertension chapter for a complete review of betablockers Beta-blockers without ISA are preferred (e.g., metoprolol, carvedilol); can be used as monotherapy or in combination with DHP CCBs, long-acting nitrates and/or ranolazine Provide mortality reduction and symptom improvement More effective than nitrates and CCBs in silent ischemia; avoid in Prinzmetal's angina Calclum Channel Blockers Preferred for Prinzmetal's (variant) angina -l- HR and contractility; DHPs -l- SVR (afterload) Generally used when beta-blockers are contraindicated or as add-on therapy to beta-blockers if continued symptoms Increase myocardial oxygen supply: all CCBs blood flow through coronary arteries Slow-release or long-acting DHPs and non-DHPs are effective; avoid short-acting DHPs (e.g., nifedipine IR) Reduce myocardial oxygen demand: non-DHPs See the Hypertension chapter for a complete review of calcium channel blockers i Nitrates Reduce myocardial oxygen demand: -l- preload (free radical nitric oxide produces vasodilation of veins more than arteries) SL tablets, SL powder or spray Recommended for all patients for fast relief of angina Increases myocardial oxygen supply: i blood flow through collateral (non-atherosclerotic) arteries Long-acting nitrates Long-acting nitrates are used when beta-blockers are contraindicated or as add-on therapy, if continued symptoms; a nitrate-free interval is required to prevent tolerance (see Nitroglycerin Formulations table on next page) Selectively inhibits the late phase Na current and -l- intracellular Ca; can decrease myocardial oxygen demand by decreasing ventricular tension and oxygen consumption CONTRAINDICATIONS Liver cirrhosis, do not use with strong CYP3A4 inhibitors or inducers Ranolazine (Ranexa) DHPs are preferred when CCBs are used in combination with beta-blockers (due to the risk of excessive bradycardia when non-DHPs are used with beta-blockers) n WARNINGS Can cause QT prolongation Acute renal failure observed when CrCI < 30 ml/min SIDE EFFECTS Dizziness, headache, constipation, nausea MONITORING ECG, K, renal function NOTES Not for acute treatment of chest pain Can use in place of beta-blockers or as add-on treatment Has little to no clinical effects on HR or BP 461 29 I ISCHEMIC HEART DISEASE Nitroglycerin Formulations Used in SIHD FORMULATIONS* SAFETY/SIDE EFFECTS/MONITORING Short-Acting Nitrates CONTRAINDICATIONS Nitroglycerin SL tablet (Nltrostat) Hypersensitivity to organic nitrates, do not use with PDE-5 inhibitors or riociguat (see Nitrate Drug Interactions) 0.3 mg, 0.4 mg, 0.6 mg Short-acting nitrates: i intracranial pressure, severe anemia, circulatory failure and shock (SL powder only) Nitroglycerin TL spray (NitroMist, Nitrolinsual) WARNINGS 0.4 mg/spray Hvpotension, headache, tachyphylaxis (J, effectiveness/tolerance with long-acting products), can aggravate angina caused by hypertrophic cardiomyopathy Nitroglycerin SL powder (GoNitro) SIDE EFFECTS Headache, flushing, syncope, dizziness 0.4 mg/packet MONITORING BP, HR, chest pain Long-Acting Nitrates NOTES Short-acting nitrates Nitroglycerin ointment 2% (Nitro-Bid) Used PRN for immediate relief of chest pain Store nitroglycerin SL tablets in the original amber glass bottle and keep tightly capped after each use (to maintain potency) Nitroglycerin transdermal patch (Minitran, Nitro-Dur) Nitrate tolerance does not develop with SL/TL products 0.1, 0.2, 0.3, 0.4, 0.6, 0.8 mg/hr Long-acting nitrates . Require a 10-12 hour nitrate-free interval to J, tolerance (longer for some I products) Nitroglycerin ER capsule (Nitro-Time) I 2.5 mg, 6 mg, 9 mg lsosorblde mononltrate IR/ER tablet I Patch: wear on for 12-14 hours, off for 10-12 hours; rotate sites; dispose of safely, away from children and pets -------- _ J Ointment: dosed BID, 6 hours apart with a 10-12 hour nitrate-free interval (Monoket, lmdur**) lsosorbide mononitrate: IR dosed BID, 7 hours apart (e.g., 8 AM and 3PM) IR: 10 mg, 20 mg ER: 30 mg, 60 mg, 120 mg lsosorbide dinitrate IR/ER (Dilatrate-SR, lsordil Titradose) IR: 5 mg, 10 mg, 20 mg, 30 mg, 40 mg ER: 40 mg I lsosorbide di nitrate: IR dosed BID (same as above) or TIO, take at 8 AM, 12 PM and 4 PM for a 14-hour nitrate-free interval (or similar) Take ER daily in the morning or BID with an 18-hour nitrate-free interval lsosorbide dlnltrate In combinati on with hydral<:1zlne is the preferred formulation for H FrEF 'IV nitroglycerin is discussed in the Acute & Critical Care Medicine chapter. **Brand discontinued but name still used in practice. Nitrate Drug Interactions Do not use long-acting nitrates in combination with PDE-5 inhibitors and riociguat; use caution with other antihypertensive medications and alcohol, as these combinations can cause a significant decrease i11 BP. o If only short-acting nitrates are used, they should not be used if a PDE-5 inhibitor was taken recently (avanafil in the past 12 hours, sildenafil or vardenafil in the past 24 hours or tadalafil in the past 48 hours). Occasionally, and with careful monitoring, nitrates can be used in an acute emergency in a patient who has recently taken a PDE-5 inhibitor. Ranolazine Drug Interactions Ranolazine is a major substrate of CYP3A4 and a minor substrate of CYP2D6 and P-gp. It is a weak inhibitor of CYP3A4, 2D6 and P-gp. Do not use with strong CYP3A4 inhibitors or inducers. Limit the dose to 500 mg BID if taking moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil). Limit simvastatin to 20 mg/day if used together. 462 RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 KEY COUNSELING POINTS See the Drug Formulations and Patient Counseling chapter for counseling language/layman's terminology. ASPIRIN Can cause: Bleeding/bruising. Dyspepsia. Allergy. Tinnitus or loss of hearing with overdose. CLOPIDOGREL Cancause: Bleeding/bruising. Thrombotic thrombocytopenic purpura (TTP). ALL NITROGLYCERIN PRODUCTS Cancause: NITROGLYCERIN PATCH The chest is the preferred appHcation site, though any area can be selected except the extremities below the knees or elbows. NITROGLYCERIN OINTMENT Measure the dose of ointment with the dose-measuring applicator (see image below) provided. Place the applicator on a flat surface, squeeze the ointment onto the applicator and place the applicator (ointment side down) on the chest or other desired area of the skin. Spread the ointment, using the dose-measuring applicator, lightly onto the skin. Do not rub into the skin. Tape the applicator into place. Can stain clothing. Cover the applicator completely. Orthostasis. Flushing and headache. Often a sign the medication is working. Usually goes away with time. Nitrate-free interval required with long-acting products. Drug interactions with phosphodiesterase-5 inhibitors. SHORT-ACTING NITRATES Take one dose at first sign of chest pain. Call 911 immediately if chest pain persists after the first dose. Continue to take two additional doses at five minute intervals while waiting for the ambulance to arrive. Do not take more than three doses within 15 minutes. NITRO-BID® (Nitroglycerin Ointment USP, 2%) INCHES I I CENTIMETERS ½ I I 1.25 1 1½ 2 I I I I I I 2.5 3.75 5 the applicator that measures the dose Nitroglycerin SL Tablets • Place the tablet under the tongue or between the inside of the cheek and the gums/teeth, and let it dissolve. Do not chew, crush or swallow. • Slight bul!Il.ing or tingling sensation is not a sign of how well the medication is working. Keep tightly capped in the original amber glass bottle and store at room temperatl.u·e. Shake out one tablet only; do not let the other tablets get wet. Select Guidelines/References 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease. Circulation. 2014;130:1749-1767. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease. Circulation. 2012;126(25):e354-e471. Nitroglycerin TL Spray Prime before first use and if not used within six weeks. • Do not shake. Press the button firmly to release the onto or under the tongue. Close your mouth after the spray. Do not inhale the spray, and try not to swallow too quickly afterward. Do not spit or rinse the mouth for 5 - 10 minutes after the dose. 463