Chapter 29 - Ischemic Heart Disease Flashcards
- What is another term for ischemic heart dx?
- How is it described?
- Angina
- 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.
What are the types of angina?
1- Stable angina, Stable ischemic heart dx (SIHD)
- Predictable chest pain
- Often triggered by exertion or emotional stress
- Relieved within minutes by rest or with nitroglycerin
2- Unstable angina (UA):
- A type of acute coronary syndrome (ACS);
- A medical emergency
- Chest pain increases (in frequency, intensity or duration)
- Not relieved with nitroglycerin or rest
3- Prinzmetal’s (variant or vasospastic) Angina:
- Chest pain caused by vasospasm of the coronary arteries
- Can occur at rest
- Can be caused by illicit drug use, particularly cocaine.
When are the classic symptoms of SIHD not present?
The classic symptoms of SIHD may not be present in:
- Women
- Elderly
- Diabetes
This can lead to misdiagnosis (GERD) or a delay in ttmt.
PATHOPHYSIOLOGY
- Imbalance between myocardial O2 demand (workload) and supply (blood flow)
- In SIHD, myocardial O2 supply is often decreased due to plaque build up (atherosclerosis) within the inner walls of the coronary arteries.
– This is known as coronary artery dx (CAD); it causes narrowing of the arteries and reduced blood flow to the heart - Myocardial O2 demand inc when the heart is working harder due to an inc HR, contractility or L ventricular wall tension [caused by inc preload (volume of blood returning to the heart) and/or afterload (systemic vascular resistance, or SVR)].
Risk factors for SIHD
- Hypertension
- Smoking
- Dyslipidemia
- Diabetes
- Obesity
- Physical inactivity.
To assess the likelihood of CAD and diagnose SIHD, a CARDIAC STRESS TEST is performed.
Diagnosis
Cardiac stress test increases myocardial oxygen demand with either:
- Exercise (walking on a treadmill or pedaling a stationary exercise bicycle) or
- IV meds (adenosine, dipyridamole, dobutamine or regadenoson (Lexiscan)
As myocardial O2 demand inc, the pt is monitored for:
- Development of sx (chest pain, dyspnea, lightheadedness)
- Changes in HR and BP
- Transient rhythm disturbances
- ST segment abnormalities on an ECG
- When the diagnosis of SIHD is certain, coronary angiography can be performed to assess the extent of atherosclerosis & need for revascularization.
EVALUATION OF SIHD
What should you monitor
- History and physical
- CBC, CK-MB, troponins (I or T), aPTT, PT/INR, lipid panel, glucose
- ECG (at rest and during chest pain)
- Cardiac stress test/stress imaging
- Cardiac catheterization/ angiography
NON-DRUG TREATMENT
1) Heart healthy diet
- Saturated fats < 7 % and trans fats < 1 % of total calories
- Adequate intake of fresh fruits and vegetables
- Low-fat dairy products
2) Maintain a BMI of 18.5 - 24.9 kg/m2, and maintain a waist circumference < 35 inches in females and < 40 inches in males.
3) Patients should engage in 30 - 60 min of moderate- intensity aerobic activity 5 - 7 d/w
4) Medically supervised programs, such as cardiac rehabilitation, are encouraged for at-risk patients at 1st diagnosis.
5) Patients who smoke should quit, and secondhand smoke should be avoided.
6) 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.
What are the treatment goals for SIHD?
- Improve function (by eliminating chest pain)
- Prevent future cardiovascular events (MI, HF)
- Reduce the risk of cardiovascular death
Drug treatment
- Antiplatelet + antianginal drug regimen
- Antiplatelet ttmt prevents platelets from sticking together & forming a clot that can block an artery & reduce blood flow to the heart.
- Antianginal ttmt dec myocardial O2 demand or inc myocardial O2 supply
- Aspirin is the recommended antiplatelet; clopidogrel (Plavix) is used when there is an allergy or other CI to aspirin.
- When do you combine aspirin with clopidogrel?
- When do you combine low dose rivaroxaban with aspirin?
- Aspirin + clopidogrel: history of stent placement or recent CABG
- Low-dose rivaroxaban (Xarelto) + aspirin is FDA-approved to reduce the risk of cardiovascular events in patients with CAD or peripheral artery disease (PAD)
What drugs are first line? What do you use other drugs?
1) BB are 1st line
2) If BB are CI or when additional Sx relief is needed use:
– CCBs (DHP and non-DHP), or
– Long-acting nitrates
3) Ranolazine is used as a substitute or in addition to BB
4) Short-acting nitroglycerin (SL) powder or translingual (TL) spray, is recommended for immediate relief of angina in all patients.
2) With what should pts be treated with also?
4) What vaccine should you do
1) SIHD is one of the atherosclerotic cardiovascular diseases (ASCVD).
2) Patients should be treated with a high-intensity statin.
3) Hypertension, heart failure and diabetes should be aggressively managed with guideline-recommended treatments, including the use of an ACE inhibitor or ARB to manage hypertension in patients with SIHD and diabetes.
4) An annual influenza vaccine is recommended; pneumococcal vaccines should be administered per ACIP recommendations
Ttmt approach for SIHD
A- Anti platelet and antianginal drugs
B- Blood pressure and beta-blockers
C - Cholesterol (statins) and cigarettes (cessation)
D - Diet and diabetes
E- Exercise and education
Antiplatelet drugs MOA
1- Aspirin:
- Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes
- This results in dec prostaglandin (PG) and thromboxane A2 (TXA2) production.
– TXA2 is a potent vasoconstrictor & inducer of platelet aggregation.
2- Clopidogrel:
- Prodrug that irreversibly inhibits P2Yl2 ADP-mediated platelet activation and aggregation
Aspirin
- Brands
- Dose
- Bayer, Bufferin, Ecotrin
+Omeprazole (Yosprala)
- Rx: ER capsule (Durlaza), delayed-release tablet (Yosprala)
- Dose: 75-162 mg daily
Aspirin CI
- NSAID or salicylate allergy
- Children & teens with VIRAL INFECTION
—> Due to the risk of Reye’s syndrome (sx: somnolence, N/V, confusion) - Rhinitis, nasal polyps or asthma (due to risk of urticaria, angioedema or bronchospasm)
Warnings with aspirin
- Bleeding
– Including GI bleed/ulceration
– Inc risk with heavy alcohol use or use with other drugs with bleeding risk (NSAIDs, anticoagulants, other antiplatelets) - Tinnitus (salicylate overdose)
Aspirin SE & Monitoring
- SIDE EFFECTS
Dyspepsia, heartburn, bleeding, nausea - MONITORING
Symptoms of bleeding, bruising
Aspirin:
1) Do we use it for SIHD? Why?
2) Why is aspirin used with low-dose xarelto?
3) What dosage form is preferred in ACS?
5) What is a risk with chronic nsaid use?
6) What is yosprala indicated for?
1) Used indefinitely in SIHD (unless contraindicated); dec incidence of Ml, CV events and death
2) Used with low-dose rivaroxaban to reduce the risk of major cardiovascular events (Ml, stroke)
3) Non-enteric coated, chewable aspirin is preferred in ACS; if only enteric-coated (EC) aspirin is available, it should be chewed (325 mg)
4) Durlaza and Yosprala should not be used when rapid onset is needed (ACS, pre-PCI)
To dec nausea, use EC or buffered product or take with food
5) PPls may be used to protect the gut with chronic NSAID use; consider the risks from chronic PPI use (dec bone density, inc infection risk)
6) Yosprala is indicated for those at risk of developing aspirin-associated gastric ulcers
Clopidogrel Brand & Dose
- Plavix
- 75 mg daily
Used in SIHD when there is a CI to aspirin; can be used in combination with aspirin
BBW with clopidogrel
Poor cyp 2c19 metabolizers
- 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.
CI with clopidogrel
Active serious bleeding (GI bleed, intracranial hemorrhage)
Warning with clopidogrel
- What should you do if the pt had an elective surgery and is on clopidogrel
- DDI?
- Bleeding risk
- Stop 5 days prior to elective surgery
- Do not use with omeprazole or esomeprazole
- Premature discontinuation (inc risk of thrombosis), thrombotic thrombocytopenic purpura (TTP)
SE & monitoring with clopidogrel
SE: Generally well tolerated, unless bleeding occurs
Monitoring: Sx of bleeding, Hgb/Hct as necessary
Dual Antiplatelet Therapy
- SIHD is usually treated with a single antiplatelet drug (aspirin or clopidogrel}.
- Dual antiplatelet therapy (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)
– Post-CABG (DAPT for 12 months) - Clopidogrel is the only P2Yl2 inhibitor recommended in SIHD.
- Aspirin is dosed at 81mg daily in DAPT regimens and is continued indefinitely at 75 - 162 mg daily after the course of DAPT is complete.
Antiplatelet Drug Interactions
■ Most drug interactions are due to additive effects with other drugs that can inc bleeding risk (anticoagulants, NSAIDs, SSRis,SNRis, some herbals).
■ Aspirin: use caution in combination with other ototoxic drugs
■ Clopidogrel: avoid in combination with CYP2Cl9inhibitors omeprazole and esomeprazole (other PPis interact less) and use caution with other CYP2Cl9inhibitors.
ANTIANGINAL TREATMENT
1) Beta-Blockers: 1st line in SIHD
2) CCB: Preferred for Prinzmetal’s (variant) angina
3) Nitrates
4) Ranolazine (Ranexa)
Beta-Blockers moa and clinical notes
- Should you titrate? Can you stop abruptly?
- What beta blocker is preferred?
- When should you avoid them?
Reduce myocardial oxygen demand:
- Dec HR
- Dec contractility
- Dec left ventricular wall tension
CLINICAL NOTES
- Start low, go slow
- Titrate to resting HR of 55-60 BPM
- Avoid abrupt withdrawal
- Beta-blockers without ISA are preferred (metoprolol, carvedilol);
- Can be used as monotherapy or in combination with DHP CCBs, long-acting nitrates and/or ranolazine
- Provide mortality reduction and sx improvement
- More effective than nitrates and CCBs in silent ischemia;
- Avoid in Prinzmetal’s angina
Beta blockers without ISA:
- Atenolol
- Bisoprolol
- Metoprolol
- Nebivolol
- Esmolol
CCB:
- When are they preferred?
- How do they work?
- When are they used?
- Do we prefer short acting or long acting DHPs?
- Do we prefer combining BB with dhp or non dhp and why?
- Preferred for Prinzmetal’s (variant) angina
- Reduce myocardial oxygen demand:
– non-DHPs dec HR and contractility;
– DHPs dec SVR (afterload) - Increase myocardial O2 supply:
– All CCBs inc blood flow through coronary arteries - Generally used when beta-blockers are CI or as add-on therapy to beta-blockers if continued symptoms
- Slow-release or long-acting DHPs and non-DHPs are effective;
- Avoid short-acting DHPs (Nifedipine IR)
- 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
Nitrates
- Reduce myocardial oxygen demand:
– Dec preload (free radical nitric oxide produces vasodilation of veins more than arteries) - Increases myocardial oxygen supply:
– Inc blood flow through collateral (non-atherosclerotic) arteries - SL tablets, SL powder or TL spray
– Recommended for all patients for fast relief of angina - 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
Ranolazine (Ranexa)
- MOA
- CI
- Warning
- SE
- Monitoring
- Notes
- Selectively inhibits the late phase Na current and dec intracellular Ca;
- Can decrease myocardial oxygen demand by decreasing ventricular tension and oxygen consumption
- CI: Liver cirrhosis, do not use with strong CYP3A4 inhibitors or inducers
- WARNINGS
– Can cause QT prolongation
– Acute renal failure observed when CrCI < 30 mL/min - SE: 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
Nitroglycerin Formulations Used in SIHD:
Short-Acting Nitrates
- Nitroglycerin SL tablet (Nitrostat)
- Nitroglycerin TL spray (NitroMist, Nitrolingual)
- Nitroglycerin SL powder
Nitroglycerin Formulations Used in SIHD:
Long-Acting Nitrates
- Nitroglycerin ointment 2% (Nitro-Bid)
- lsosorbide mononitrate IR/ER tablet
Nitroglycerin Formulations Used in SIHD:
CONTRAINDICATIONS
- Hypersensitivity to organic nitrates,
- Do not use with PDE-5 inhibitors or riociguat
Short-acting nitrates:
- Inc intracranial pressure
- Severe anemia
- Circulatory failure and shock (SL powder only)
Nitroglycerin Formulations Used in SIHD:
WARNINGS
- Hypotension
- Headache
- Tachyphylaxis (dec effectiveness/tolerance with long-acting products)
- Can aggravate angina caused by hypertrophic cardiomyopathy
Nitroglycerin Formulations Used in SIHD:
SE & Monitoring
SIDE EFFECTS
Headache, flushing, syncope, dizziness
MONITORING
BP,HR, chest pain
Short-acting nitrates notes
- 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)
- Nitrate tolerance does not develop with SL/TL products
Long-acting nitrates notes
Require a 10-12 hour nitrate-free interval to dec tolerance (longer for some products)
■ Patch: wear on for 12-14 hours, off for 10-12 hours; rotate sites; dispose of safely, away from children and pets
■ Ointment: dosed BID, 6 hours apart with a 10-12 hour nitrate-free interval
■ lsosorbide mononitrate: IR dosed BID, 7 hours apart (e.g.,8 AM and 3PM)
■ lsosorbide dinitrate: IR dosed BID (same as above) or TID, take at
8 AM, 12 PM and 4 PM for a 14-hour nitrate-free interval (or similar)
■ Take ERdaily in the morning or BID with an 18-hour nitrate-free interval
lsosorbide dinitrate in combination with hydralazine is the preferred formulation for HFrEF
Nitrates DDI
- 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 in BP.
- 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
– 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.
(They both lower BP which is dangerous)
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 (Diltiazem, verapamil).
- Limit simvastatin to 20 mg/day if used together.
ASPIRIN
counseling
■ Can cause:
o Bleeding/bruising
o Dyspepsia
o Allergy
o Tinnitus or loss of hearing with overdose
CLOPIDOGREL
counseling
■ Cancause:
□ Bleeding/bruising.
□ Thrombotic thrombocytopenic purpura (TTP).
ALL NITROGLYCERIN PRODUCTS
counseling
■ Can cause:
o Orthostasis.
o 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
counseling
■ 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 5 min intervals while waiting for the ambulance to arrive.
– Do not take more than three doses within 15 min
Nitroglycerin SL Tablets
counseling
■ 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 burning 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 temperature. Shake out one tablet only; do not let the other tablets get wet
Nitroglycerin TL Spray
■ Prime before first use and if not used within six weeks.
- Do not shake.
- Press the button firmly to release the spray 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 min after the dose.
NITROGLYCERIN PATCH
■ The chest is the preferred application 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 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.
