Lecture 9,10 Stable Ischemic Heart Disease Flashcards
What is ischemic heart disease?
term used to describe narrowing of coronary arteries that affects the blood supply to the heart
this = coronary artery disease with ischemia
not all pt with this have sx of angina
pain with exertion/emotional stress, ECG changes +/- at rest (non-specific) present with exertion
Why does IHD only cause chest pain some of the time (coronary blood flow)?
blood flow to myocardium is controlled microcirculation (dilating/constricting) rather than large coronary arteries (under normal conditions)
> 50-75% occlusion is required to cause ischemia with exertion
> 90% occlusion is required to affect resting blood flow
What tests aid in the diagnosis of SIHD?
ECG and exercise stress test (EST)
Myocardial Perfusion Imaging - nuclear medicine scan, MIBI/PET scan: radiotracers, uptake in muscle, images heart at rest and during stress (difference in uptake)
Coronary Angiography - gold standard, direct visualization of arteries (2D, not inside lumen), access through femoral or radial artery, contrast dye + x-ray, invasive ⇒ risk of MI, stroke, arrhythmia, perforation, bleeding
What are some invasive revascularization procedures that can be used for IHD?
percutaneous coronary intervention (PCI) (aka stenting)
Coronary artery bypass graft (CABG) surgery
What are risk factors which can be modified in tx of IHD?
healthy weight, exercise, smoking cessation, HTN, dyslipidemia, DM
What are tx for thrombosis prevention in IHD patients?
antiplatelet agents: ASA
ALL patients unless contraindicated should be on one (is first line)
Dosage: 80-325 mg QD (low dose preferred)
AE: increases risk of major intracranial and GI hemorrhage
Clopidogrel: should be used if ASA intolerance/contra
Dosage: 75 mg QD
AE: increases risk of major intracranial and GI hemorrhage
When should dual antiplatelet agents be used in IHD?
not indicated in most patients for STABLE disease (benefit = harm)
can use if: high risk pt with low risk of bleeding where benefits thought to outweigh risks, multiple events occurred already, younger age, disease in multiple vascular beds (CAD, CVA, PAD)
is common post ACS (12 months (can be up to 36) and post PCI 6-12 months)
What treatment should be used for vascular protection in IHD?
ACEi - rationale: decrease progression of atherosclerosis and neo-intimal formation, plaque stabilization, ventricular remodeling, endothelial fxn, fibrinolysis
consider in ALL patients with this disease in the absence of chronotropic incompetence (CI), especially those with other indications: post-MI, systolic HF (HFrEF)
can also use ARBs
What are contraindications for ACEi/ARBs?
pregnancy, bilateral renal artery stenosis, hypersensitivity, hx of angioedema with prior agent
What are some things which should be noted when thinking about if symptom control is needed in IHD?
severity of attacks, impact on exercise tolerance, impact of ADLs and on QoL,, frequency of attacks
What treatments are indicated for symptom control in IHD?
First Line: beta-blockers
Second-Line: CCBs, long acting nitrates
Third Line: ranolazine
How do beta-blockers enact their anti-ischemic effects?
reduce HR and contractility = lowering MvO2
slight decrease in BP (through reducing CO, inhibition of renin) = reduced afterload, lowering myocardial wall stress and MvO2
doesn’t generally improve O2 supply
Cardiac Effects: decrease sympathetic tone ⇒ chronotropy (HR), inotropy (contractility), dromotropy (electrical conduction), lusitropy (relaxation)
Vascular Effects (Minor): mild vasoconstriction (unopposed alpha effects), blocking B2Rs removes vasodilatory influence that normally opposes the alpha mediated vasoconstriction
What are the clinical effects of beta-blockers in IHD?
delays or eliminates angina during exercise - limits in HR and BP during exercise
decreases needs for short acting NTG
decrease frequency of angina
no specific agent is superior, however avoid acebutolol in pt with intrinsic sympathomimetic activity (ISA) and sotalol (anti-arrhythmic)
may worsen vasospastic angina (unopposed alpha blockade)
How should beta-blockers be initiated in IHD symptomatic control?
Baseline: BP (SBP > 100), HR (> 60), euvolemic (HF), no contras
Titration: to HR (55-60 or lower if no sx of bradycardia) or sx relief, avoid abruptly stopping due to risk of rebound tachycardia
What are contraindications for the usage of beta-blockers?
reactive airway disease (ex. asthma) - caution in COPD (use B1 selective)
secondary or tertiary heart block
decompensated HF
severe PAD
pheochromocytoma (without alpha blockade), hypersensitivity
What are AEs of beta-blockers?
fatigue, insomnia, vivid dreams, depression
bradycardia, hypotension, decreased exercise tolerance, heart block
bronchospasm (> non-selective agents)
mask hypoglycemia, increased BG and TG, lower HDL-C
impotence, decreased libido, cold extremities
What beta-blockers are B1 selective?
metoprolol, atenolol, bisoprolol
How does cardio-selectivity work with beta-blockers and where can we benefit with it?
can minimize (via not blocking B2): bronchospasm, potential hyperglycemia, blunt recovery from hypoglycemia, potential aggravation of intermittent claudication or Raynaud’s phenomenon
is dose dependent and at higher doses the selective agents lose their relative selectivity
the dose at which this happens varies from pt to pt
How do CCBs enact their anti-ischemic effects?
NDHP: decrease inotropy (demand, contractility), decrease chronotropy (supply and demand, HR), decrease dromotropy (supply and demand, conduction velocity), all together = decrease MvO2
competitive antagonists of L-type Ca2+ channels = decreased Ca2+ for contractile elements (SA and AV node) ⇒ SM relaxation and vasodilation
DHP: vasodilation for coronary and systemic (supply and demand), decrease arterial resistance and afterload = lowering myocardial wall stress and MvO2, coronary artery dilation = improved O2 supply (mainly in vasospastic angina)
How should CCBs be initiated in IHD symptomatic control?
short acting DHPs may increase risk of adverse CV events from rapid BP drops, long acting are effective at relieving sx
Baseline: NDHP - BP (SBP > 100), HR (> 60), no contras,, DHP - ensure adequate BP to start agent
Titration: NDHP - to HR (55-60 or lower if no sx of bradycardia) or sx relief
DHP - sx relief, while monitoring BP
What are the different doses for CCBs in angina/HTN?
NDHP: Verapamil - RR 80-120 mg TID-QID (short acting, avoid), SR 180-480 mg QD
Diltiazem - RR 30-90 mg TID-QID (short acting, avoid), SR 90-180 mg BID, CD 120-360 mg QD
DHP: Nifedipine - PA 20-40 mg BID, XL 30-90 mg QD
Amlodipine - 2.5-10 mg QD
Felodipine - 2.5-10 mg QD
What are AEs of CCBs?
dizziness, fatigue, H/A,, hypotension, brady/tachycardia, heart block, decreased exercise tolerance
constipation (verapamil)
rash (diltiazem), flushing (DHP)
peripheral edema (DHP, dose related, 20%)
What are contraindications and drug interactions noted with CCBs?
Contra: 2nd or 3rd degree heart block or sick sinus syndrome without pacemaker (NDHP), hypotension, bradycardia (NDHP), HFrEF (except amlodipine)
Intx: digoxin ⇒ decreased HR and increased digoxin (verapamil/diltiazem) ⇒ monitor HR, monitor digoxin
beta-blockers ⇒ decreased HR (verapamil/diltiazem), lower BP ⇒ avoid use, monitor HR, BP
Diltiazem is CYP3A4 substrate and inhibitor
Verapamil is CYP3A4 substrate and inhibitor, 1A2 and 2C substrate, P-glycoprotein,, Felodipine is CYP3A4 inhibitor
How do nitrates enact their anti-ischemic effects, whats its MOA, and clinical effects?
Effects: venous dilation ⇒ decreased preload = decreased myocardial wall tension = decreased MvO2
lower preload = decreased diastolic wall stress = improved subendocardial blood flow = improved regional flow distribution
mild coronary vasodilation ⇒ may improve O2 supply
mild afterload reduction
MOA: vasodilation, converted to NO by endothelium, activates cGMP = decreased cellular Ca2+ = SM relaxation and vasodilation
Clinical: improved exercise tolerance, time to onset of angina, ischemic threshold
How should rapid acting NTG be used?
stop and sit down (avoid presyncope/syncope), after one dose if NO relief or gets worse ⇒ call 911
if improves but doesn’t resolve wait 5 minutes and take second dose, if NOT resolved in 5 minutes ⇒ call 911 and take another dose
can continue to take every 5 min until EMS arrives
What are AEs of nitrates?
H/A, dizziness
hypotension, reflex tachycardia, palpitations, syncope
N/V, diarrheh
weakness
flushing, rash
What are contraindications and drug intx with nitrates?
Contra: severe aortic stenosis (preload dependent)
Intx: sildenafil, vardenafil, tadalafil ⇒ inhibits breakdown of NO by PDE5i, if coadmin = increase risk of life-threatening hypotension ⇒ contra at least 24 hours with sildenafil and vardenafil, and at least 3-4 days with tadalafil
Ranolazine for IHD (indication, MOA, dose, AE, intx)
Indication: approve second-line anti-anginal for add-on tx of sx pt with angina
MOA: inhibits late Na+ influx during repolarization in myocytes ⇒ reduces IC Na+ conc ⇒ lowers Ca2+ influx ⇒ lowers ventricular diastolic wall tension = lowering of MvO2
doesn’t impact HR r BP (ideal add-on), can prolong QT at higher doses
Dose: ER 500 mg BID, increased to max 1000 mg BID in 2-4 weeks based on sx
AE: constipation, nausea, dizziness, H/A, prolong QT, use with caution in CrCl < 50, contra in hepatic cirrhosis
Intx: avoid with concomitant QT prolonging agents,, is substrate or CYP3Ar and p-glycoprotein ⇒ contra with strong CYP3A4 inducers (phenytoin, carbamazepine, rifampin) and strong inhibitors (ketoconazole, clarithromycin, antiretrovirals)
is also weak inhibitor of CYP3A4 and p-glycoprotein
Colchicine for IHD (MOA, AE, intx)
MOA: anti-inflammatory, inhibition of tubulin polymerization, alterations in leukocyte responsiveness
used the LoDoCo2 trial
can potentially be used as add-on to standard tx (ASA, statins, ACEi)
AE: neuropathy, bone marrow suppression, diarrhea, N/V, myalgia, myositis, rhabdo
Intx: narrow index, is a CYP3A4 substrate and p-glycoprotein
should be dosage adjusted in mild-moderate cirrhosis and CrCl < 30 (some suggest < 60)
