Ischemic Heart Disease (IHD) Flashcards
Coronary Artery Disease (CAD) = Coronary Heart Disease (CHD)
Any vascular disorder that narrows or occludes coronary arteries
Usually a manifestation of atherosclerosis
Ischemic Heart Disease (IHD)
Blanket term for a number of syndromes
Occurs due to increase myocardial O2 demand or decrease in O2 supply to heart
Angina Pectoris
Clinical syndrome, characterized by pain or discomfort primarily in the chest, but may also be described in the jaw, shoulder, back or arm
Most commonly due to ischemic heart disease; a symptom of IHD
Subsets of Angina
Prinzmetal’s “Variant” Angina
Silent myocardial ischemia
Prinzmetal’s “Variant” Angina
Occurs at rest
Due to coronary spasm
Reversed with nitroglycerin and calcium channel blockers
Silent myocardial ischemia
Type I (Less common)
–> Defective anginal warning system
Type II (more common)
–> Angina may be a poor indicator of ischemia
–> Autonomic neuropathy, higher threshold for pain, excess endorphins
–> Indicates higher risk patient
Stable or Exertional Angina
Exertional pain lasting < 20 min, relieved by rest
ACS (unstable Angina, STEMI, or NSTEMI)
Pain occurring at rest lasting > 20 minutes
Modifiable Risk Factors
Cigarette smoking Dyslipidemia (elevated LDL or total; reduced HDL) Diabetes mellitus Hypertension Physical inactivity Obesity (BMI >30 kg/m2) Low daily fruit and vegetable consumption Alcohol overconsumption
Non-modifiable Risk Factors
Gender (men and postmenopausal women)
Age (Men >45; Women >55)
Family History (1st degree relative Father <55; Mother <65)
Environment (climate, air pollution, drinking water)
Signs and symptoms associated with angina (Subjective)
Shortness of breath (SOB), dyspnea on exertion
(DOE), diaphoresis, palpitations, chest pain (CP),
lightheadedness
Signs and Symptoms associated with angina (Objective)
BP, HR, decreased oxygen saturation on ABG,
ECG changes: ST segment elevation or
depression, or T wave inversions, troponins
PQRST
Precipitating factors and palliative measures
Quality of pain
Region and radiation of pain
Severity of pain
Temporal pattern
Non-invasive measure of MVO2:
Double product (DP) = HR x SBP
IHD is the result of an _____ in myocardial
oxygen demand and _____ supply
increase, decreased
IHD oxygen supply
decrease arterial PO2
decrease diastolic filling time
decrease coronary blood flow
IHD oxygen demand
increase HR
increase myocardial contractility
increase ventricular wall tension
increased demand (non-cardiac)
Hyperthermia Hyperthyroidism Sympathomimetic toxicity Hypertension Anxiety B- agonists
increased demand (cardiac)
Hypertrophic cardiomyopathy Aortic stenosis Dilated cardiomyopathy Tachycardia
decreased supply (non-cardiac)
Anemia Hypoxemia Sickle cell disease Sympathomimetic toxicity Hyperviscosity
decreased supply (cardiac)
Aortic stenosis
Hypertrophic
cardiomyopathy
Short term treatment goals
Reduce or prevent
symptoms that limit
exercise capability and
impair quality of life
Long term treatment goals
Prevent CHD events (MI,
HF, stroke, death) and
extend the patient’s life
Treatment outcomes
Prevent ACS and death Alleviate acute symptoms of myocardial ischemia Prevent progression of the disease Reduce complications of IHD Avoid or minimize adverse treatment effects
Class 1
is recommended/is indicated
Class 2 a
should be considered
Class 2 b
may be considered
Class 3
is not recommended
Level of Evidence A
Data derived from multiple randomized clinical trials or meta-
analysis
Level of Evidence B
Data derived from a single randomized clinical trial or large non-
randomized studies
Level of Evidence C
Consensus of opinion of the experts and/or small studies,
retrospective studies, registries
Non-pharm treatment options
Lifestyle modification
PCI (symptom relief no mortality benefit)
CABG (symptom relief and mortality benefit)
Medication treatment
Acute pain relief
SL NTG
Medication treatment
Maintenance
Nitrates
B-blockers with prior MI
CA blockers or long-acting nitrates
Ranolazine
Aspirin or clopidogrel if aspirin is contraindicated
ACE inhibitor to pts w/ CAD and DM or LV systolic dysfunction
LDL lowering therapy
Treatment Algorithm:
Lipid lowering therapy
Consider in all patients; especially those with elevated LDL/ASCVD risk: statin
Treatment Algorithm:
Lifestyle modification
Diet, exercise, weight loss, smoking cessation
Treatment Algorithm:
Immediate release nitrate
NTG SL or spray
Treatment Algorithm:
Select appropriate anti-platelet therapy
Aspirin 81 mg +/- clopidogrel
Treatment Algorithm:
Assess Comorbidities
If DM, HTN, and/or CKD
ACEi or ARB
Treatment Algorithm:
Assess Comorbidities
If prior MI and/or LV dysfunction
ACEi or ARB +BB
Treatment Algorithm:
Assess Comorbidities
if prinzmetal or variant angina
consider CCB or LA nitrate
Treatment Algorithm:
Select Antianginal therapy
BB, CCB, or LA nitrate
if ineffective, add CCB or BB (if not first line) or LA nitrate or ranolazine
if still ineffective, consider triple therapy
Effect of Drug Therapy on MVO2: Nitrates
HR: increase
contractility: 0
systolic pressure: decrease
LV volume: large decrease
Effect of Drug Therapy on MVO2: BB
HR: large decrease
contractility: decrease
systolic pressure: decrease
LV volume: increase
Effect of Drug Therapy on MVO2: Nifedipine
HR: increase
contractility: 0 or decrease
systolic pressure: 0 or decrease
LV volume: 0 or decrease
Effect of Drug Therapy on MVO2: Verapamil
HR: decrease
contractility: decrease
systolic pressure: decrease
LV volume: 0 or decrease
Effect of Drug Therapy on MVO2: Diltiazem
HR: large decrease
contractility: 0 or decrease
systolic pressure: decrease
LV volume: 0 or decrease
Ways to reduce Myocardial Ischemia/Angina
Pharmacotherapy with Anti-Ischemics
• Reduce workload of heart
Three major categories:
• Nitrates, Beta-blockers, Calcium Channel Blockers
–> Additionally, Ranolazine
Ways to reduce Myocardial Ischemia/Angina
Improve Coronary Blood Flow Mechanically
Percutaneous Coronary Intervention (PCI) • Placement of coronary stent --> Bare-metal (BMS) --> Drug-eluting (DES) • Bypass Graft Surgery (CABG)
Nitrates (O2 supple and demand)
O2 supply
–> increase coronary blood flow
O2 demand
- -> no charge HR
- -> no change contractility
- -> decrease ventricular wall tension
Nitrates immediate use
Nitroglycerin (Nitrostat)
Formulation SL tab, spray
Nitrates Immediate Release
ISDN (isordil)
ISMN (Ismo Monoket)
Nitrates Sustained Release
ISDN (Isordil Titradose Dilatreate- SR)
ISMN (Imdur)
ISMN has (high/low) bioavailability and a longer/shorter half-life than ISDN
high
longer (4-6 hours)
Rationale for Nitrate use
Restore balance between supply and demand
Prevent morbidity and mortality
Isosorbide third line for chronic prophylaxis/treatment
Use BB and CCB first
May use in combination with BB or CCB
Should not be used as monotherapy due to the lack of 24-hour coverage
Nitrate mechanism of action
Converted to nitric oxide
Venous vasodilation predominantly
Coronary artery vasodilation
May increase supply and reduce demand
Nitrates ADR/monitoring
ADR: Hypotension, headaches, flushing
Monitor: BP, HR, PRN usage, anginal symptoms
Nitrates drug interactions
Contraindicated with PDE5 inhibitors
- -> within 24 hours of sildenafil, vardenafil
- -> within 48 hours of tadalafil
Nitrate-free interval
for chronic use with isosorbide
dinitrate or mononitrate due to loss of effectiveness with
continuous exposure
Nitrate free period: at least 10-14 hours
Typically dosed ~7am and no later than 5pm
NTG is the only anti-ischemic used for ____outpatient relief
immediate
Nitrate Acute treatment
Sublingual tablet or Lingual spray
Nitrates
For non-trauma-related chest discomfort/pain:
One NTG dose, if pain unimproved or worsening after
5 minutes, call 911. May take second dose of NTG.
Store in original container
Nitrate
Prophylaxis
Take immediately before planned exercise/exertion
Limited evidence to support use of long-acting nitrates
Tolerance → oxidative stress, endothelial
dysfunction, and sympathetic activation
NTG storage considerations
keep in original container Do not store in bathroom Remove cotton plug prior to use Keep with patient at all times Take 1, if not working within 5 minutes call 911, take second
Beta Blockers (O2 supply and O2 demand)
O2 supply --> no change in coronary blood flow O2 demand --> decrease HR --> decrease contractility --> decrease ventricular wall tension
rationale for BB
Decrease mortality
Effective in improving anginal symptoms
Decreased silent ischemia episodes
First line for post-MI as well as no prior MI
BB mechanism of action
Decrease cardiac workload
Reduce heart rate by β-1 blockade
BB ADR/monitoring
ADR: Hypotension, bradycardia, impaired glucose
metabolism, bronchospasm, peripheral
vasoconstriction/intermittent claudication
Monitor: HR, BP, PRN nitrate usage, anginal
symptoms, rescue inhaler use (asthmatics), glucose
intolerance (DM)
____ reduction is the best predictor of efficacy
as an anti-ischemic agent (50-60 bpm resting HR, ≤
100 bpm exercise HR)
Heart Rate
Non-selective beta-blockers additionally block β-2
receptors in the periphery
May result in blood vessel vasoconstriction and
pulmonary bronchospasm
Maximum doses of β-1 selective agents can also
cause these effects
Beta-blockers with intrinsic sympathomimetic activity
(ISA) are inappropriate for chronic ischemia
Stimulate β-1 receptors (increase HR)
All beta-blockers are INAPPROPRIATE for
Prinzmetal’s (variant) angina
Not vasodilators. Inappropriate for vasospasms
Caution in cocaine induced angina
All beta-blockers are INAPPROPRIATE for
Prinzmetal’s (variant) angina
Not vasodilators. Inappropriate for vasospasms
Caution in cocaine induced angina
Abrupt discontinuation of beta-blockers should be
avoided
May result in reflex tachycardia and ischemia
Calcium Channel Blockers (O2 supple and O2 demand)
O2 supply
–> increase coronary blood flow
O2 demand
–> decrease HR (Verapamil/Ditilazem only)
–> decrease contractility (Verapamil/Ditilazem only)
–> decrease Ventricular wall tension
Rationale for CCB
Second line to beta-blocker use if they are contraindicated or stopped due to ADR
May use in combination with BB when BB alone is not effective
Drug of choice in Prinzmetal’s (variant) angina
CCB mechanism of action
Decrease coronary vasospasm via blocking calcium receptors in vascular smooth muscle
CCB ADR/Monitoring
ADR: Constipation, lower extremity edema, hypotension, bradycardia
Monitor: HR (non-dihydropyridine CCBs), BP, PRN nitrate usage, anginal symptoms
Non-dihydropyridines are more likely to ___ HR
bradycardia
slow
Verapamil, Diltiazem
Rationale for Ranolazine
Inadequate response with other anti-anginal agents
In combination with standard therapy
Ranolzaine MOA
Reduces calcium overload through inhibition of the late
sodium current
Minimal effects on HR and BP
Ranolzaine Dosing
Start: 500 mg po BID & may titrate up to 1000 mg po BID
Ranolazine ADR/monitoring
ADR: Constipation, headache, nausea, dizziness
Monitor: QT interval, hepatic function
Ranolazine contraindications
Contraindications:
Significant hepatic disease
Potent CYP 3A4 inhibitors
(ketoconazole, clarithromycin, protease inhibitors)
Potent CYP3A4 inducers
(rifampin, phenobarb, phenytoin, carbamazepine, St. Johns wort)
Caution w/ potent/ moderate potent CYP3A4 inhibitors
Diltiazem or verapamil: Limit ranolazine dose to 500mg bid
Simvastatin max dose of 20mg daily
(any ranolazine dose)
Metformin max dose of 1700mg daily
(only for max dose ranolazine 1000mg po bid)
P-glycoprotein substrate
Increased digoxin levels – monitor closely
Rationale for Aspirin
Reduces stroke, MI, or vascular death in patient with ASCVD
First line choice in patients with CAD, Class I recommendation
Aspirin MOA
Irreversibly blocks COX-1 activity for life of platelet
Inhibits thromboxane A2 production
Aspirin dosing
81mg po once daily
Pearl: Rivaroxaban 2.5 mg bid + Asa 81 mg daily led to 24% RR CV death,
MI, stroke vs Asa alone
May consider in patients with vascular disease, HF, DM, moderate renal
impairment
Not in AHA guidelines/in ADA guidelines; clinical updates &uptake slow
Aspirin
Adverse Drug Reactions/Monitoring:
ADR: bleeding, bruising, hemorrhage
Monitoring: hemoglobin, hematocrit, sx of bleeding
NSAID timing
Take ibuprofen/ naproxen at least 30 minutes after ASA dose or at least 8 hours prior to ASA dose
Rationale for clopidogrel
For patients unable to take aspirin due to allergy or intolerance
Reduces stroke, MI, or vascular death in patient with ASCVD
Second line choice in patients with CAD
Clopidogrel MOA
Inhibits ADP receptor-mediated platelet activity
Must be metabolized to active metabolite
Clopidogrel dosing
75mg once daily
Clopidogrel ADR/monitoring
ADR: bleeding, bruising, hemorrhage
Monitoring: hemoglobin, hematocrit, sx of bleeding
Risk factors that increase bleed risk
A history of previous gastrointestinal bleeding or peptic ulcer
disease or bleeding from other sites
Age >70 years
Female sex
Lean body weight
Thrombocytopenia
Coagulopathy
CKD; DM
Warfarin use
ONLY add a third anti-anginal drug if:
2 drugs do not control symptoms
Patient is awaiting revascularization
Revascularization is not appropriate or acceptable
