Case 2: Angina - Coronary Artery Disease Flashcards
Risk factors for development of ischaemic heart disease
Modifiable
- Obesity
- Diabetes mellitus
- Dyslipidaemia (^TC, ^LDL, ^TG) : decreased HDL
- Cigarette smoking
- Hypertension
- Physical inactivity
Non-modifiable
- Age (<45 men, <55 women), 1/5 in older people
- Gender (men 4-5 x in mid 30s, postmenopausal women)
- Family history of premature CAD
- Race
Major determinants of myocardial O2 demand & factors that control coronary blood flow
○ Hypertension leads to increase in afterload which causes increase in myocardial oxygen demand
- Atheromatous plaques (buildup of cholesterol) –> cause narrowing of lumen of arteries –> limit blood flow to myocardium = increased myocardium oxygen demand
Factors that control coronary blood flow
- In arteries or cardiac chambers: turbulence = key cause
○ Narrowing (caused by atherosclerosis)
○ Aneurysms
○ Infarcted myocardium
○ Abnormal cardiac rhythm or valvular heart disease
- In veins, statis = important cause ○ Failure of right side of heart ○ Immobilisation ○ Compressed veins ○ Varicose veins ○ Blood viscosity (e.g. sickle cell anaemia, dehydration)
Differentiate btwn pathophys of stable CAD and ACS
Stable coronary artery disease (CAD)
- Plaque builds up in arteries
- Angina: atherosclerotic plaque –> narrowing coronary arteries –> ischemia –> chest pain
- Atherosclerotic plaque building up - obstructing oxygen supply to myocardium of heart
- Chest pain - mismatch of demand and supply
- Plaque —> ACS
Acute coronary syndrome (ACS)
- Myocardial dysfunction due to infarction or ischemia
- Plaque ruptures and form thrombus –> break off and form embolism —> obstruct blood flow in coronary arteries
- STEMI or non-STEMI
Clinical presentation of stable CAD : symptoms, signs
○ Chest pain - often but not always
- Constricting discomfort, pressure/ tightness in front of chest
- May radiate to neck, lower jaw/teeth, arms (wrist/fingers) and epigastrium (upper abdominal area)
○ Precipitated by activities that increase HR and BP —> increase MO2 demand
- E.g. exercise, emotion, stress
○ Pain is relieved by rest or GTN <5 minutes
Treatment options in angina (symptom control)
- antiplatelet therapy
- Beta blockers
- CCB
- Nitrates
Medical therapy:
- Antianginal therapy: First line = BB or CCB (dihydropyridine) if low HR or intolerance of BB
Second line: Long acting nitrates - ivabradine
Short acting nitrate: pain relief
Lifestyle management:
- diet, exercise, weight reduction, smoking cessation
Risk factor management
- BP control
- diabetes control
- sleep apnoea treatment
Goals of therapy - angina
i) Short term goals of therapy (acute management)
- Relieve symptoms and prevent/reduce episodes of angina
- Goal: improve supply and or reduce demand, exercise tolerance (exercise induced ischemia) and QoL
ii) Long term goals (secondary prevention)
- Prevent complications/progression
- MI, HF, cardiac arrhythmia, stroke, mortality associated w CAD
- Extend patient’s life and QoL
Role of revascularization in angina
- PCI or CABG
Early revascularisation is selected high risk patients may be considered
Angina: Nitrates
- MOA, S/E
○ Stop/ relieve symptoms
○ Short acting (e.g. GTN SL-spray or SL-tab)
- Immediate relief of symptoms/pain
- Most commonly used
○ Long acting (e.g. nitroglycerin, isosorbide mono/dinitrate)
- Second line
- Prophylactic/ prevention of angina
→ MOA: provide exogenous source of NO
- Mediates vasodilator effect
- NO = EDRF (endothelial derived relaxing factor) –> vascular smooth muscle relaxants - veins + arteries
- Venodilator (predominantly)
- Dilates veins
- Decrease venous return + preload to heart = reduced LVEDP = reduced workload
- Decrease myocardial oxygen requirement
- Arterial dilation (at higher doses)
- Flow past stenosis + increased collateral flow
- Increased O2 supply
→ S/E
- Tolerance (continuous exposure)
- Hypotension
- Headache
- Flushing
- May induce tachycardia
→ Have nitrate free period (~10-14 hrs)
Should coincide w period of lowest risk of infarction
Angina: BB
- MOA, S/E
○ First line for exertional angina after MI - limit heart rate response to exercise
○ Benefit in those with stable CAD is less certain
○ Prevent symptoms occurring
○ Cardioselective (Beta 1 receptors)
○ E.g. bisoprolol, metoprolol
→ MOA: decrease HR + force of contraction
- Decrease HR = increase diastole time = increase oxygen supply to myocardium - Decreases workload --> decrease O2 demand
→ Monotherapy or in combo w Nitrates or CCB
- Choice depends on comorbidities - If BB not successful --> try combo (e.g. BB + CCB), or CCB + long acting nitrates if BB C/I
→ S/E
Fatigues, slow heartbeat, hypotension (vasodilation effect), impotence, depression
Angina: CCB
- MOA, S/E
First line option for treatment (as well as BB)
- Indicated for those who cant tolerate/ insufficient control of ischaemic symptoms on BB alone
Non-dihydropyridine
- Affect conducting tissues
- E.g. diltiazem/verapamil
Dihydropyridine
- No effect on conducting tissues
E.g. amlodipine, felodipine, nifedipine
Angina: Antiplatelet therapy (secondary prevention)
- MOA
→ Inhibiting platelet activation, aggregation –> reduce thrombus formation + risk of HA
→ Platelet activation and aggregation = driver for symptomatic coronary thrombosis
○ Aspirin - inhibit Cox-1 –> thromboxane production
- Protective effect in people w increased risk of occlusive vascular events/ have CVD events already
○ Oral P2Y12 inhibitors
- Inhibit P2Y12 receptor (plays key role in platelet activation + amplification of thrombus formation)
- E.g. Clopidogrel (alternative to aspirin)
- Adjunct therapy following PCI/stenting
- Glycoprotein IIb/IIIa inhibitors
- Adjunct therapy to PCI
Differences in pharmacological effects, including side effects and potential for drug-drug interactions, between non-dihydropyridine and dihydropyridine CCB’s
Benefits of CCB
- Increase exercise duration
- Reduce episodes of angina + frequency of nitroglycerin use
- Not shown to have mortality benefit in patients with stable CAD
Non-dihydropyridine
○ Less selective, reduce cardiac conduction + HR + act on vascular smooth muscle
○ Blocks AV node
○ Slow HR –> decrease demand + increase supply
○ Decrease myocardial contractility = decrease demand
○ Dilate peripheral blood vessels = decrease afterload = decrease cardiac work = decrease oxygen demand
○ Dilate coronary arteries = increase myocardial oxygen supply
→ Affects conducting tissues
→ S/E: bradycardia, hypotension
Verapamil
- Avoid in patients taking BB due to risk of heart block
- Avoid in those with heart failure bc of negative inotropic effect
Diltiazem:
- Low adverse effect profile - modest negative inotropic effect
- Care in combo w BB in patients with left ventricular dysfunction
Dihydropyridine
○ Act selectively on vascular smooth muscle to cause vasodilation, little effect on myocardial cells
○ Dilate peripheral blood vessels = decrease afterload = decrease cardiac work = decrease O2 demand
○ Dilate coronary arteries = increase myocardial O2 supply
→ Greater vascular selectivity + minimal negative inotropic properties
→ SAFER for those with left ventricular dysfunction
Amlodipine
- Effective od antianginal drug - can use in combo with BB
Long acting Nifedipine
- Antianginal drug + most effect when used in conjunction w BB
- CI: severe aortic stenosis, obstructive cardiomyopathy and heart failure
Short acting Nifedipine
- Rarely used as monotherapy due to reflex tachycardia –> worsen ischaemia + associated w dose related increase in mortality
- Should AVOID
S/E: hypotension
Formulation options for glyceryl trinitrate
Glyceryl trinitrate (GTN)
- Nitroglycerin
- Low oral bioavailability and unpredictable
- Sublingual route: avoids first pass metabolism (goes straight into blood)
Formulation options
○ Sublingual tablets (lycinate)
- Treatment of choice for rapid relief of acute symptoms and anticipated angina
- Tmax: 4.9 min
- Absorbed in sublingual mucosa
- Take effect within couple of minutes
- Can be discarded w resolution of chest pain to minimise adverse effects - headache
○ Spray (Nitrolingual pump spray)
- Equally effective as tablets
- Rapidly absorbed from mouth mucosa (tmax 4 min)
- Plasma t1/2 = 2.5-4.5 min
- Route: sublingually
- Longer shelf life –> more convenient for those w infrequent symptoms of angina
Transdermal patch
Role of revascularisation in ischaemic heart disease
○ Patients with stable angina - not common procedure
○ Not pharmacotherapeutic interventions –> not within the scope of pharmacists’ practice
Revascularization of ischemic myocardium
- Improves left ventricular regional and global mechanical and metabolic function
Patients who may benefit from revascularization include:
▪ Those at high-risk, e.g. patients with symptomatic multi-vessel disease, proximal left anterior descending or left main artery disease, left ventricular systolic dysfunction, diabetes or a large ischaemic burden (referring to all angina episodes, including silent angina).
▪ Those who have failed to respond to pharmacological treatment, i.e. patient is still experiencing symptoms while on two antianginal drugs
.
CABG:
• A section of blood vessel from another part of the body (usually chest, arms or legs) is removed and used to re-route blood around a narrowed or blocked artery to improve blood flow and oxygen supply to the heart.
• The blood vessel is attached or grafted to the coronary artery above and below the narrowed area. This creates a detour or bypass around the blocked artery leading to the heart.
PCI:
• Procedure used to open blocked coronary arteries caused by coronary artery disease. It restores blood flow to the heart muscle without open-heart surgery
• Can be done in an emergency setting, such as a heart attack
A long, thin tube (catheter) is put into a blood vessel and guided to the blocked coronary artery. The catheter has a tiny balloon at its tip. Once the catheter is in place, the balloon is inflated at the narrowed area of the heart artery. This presses the plaque or blood clot against the sides of the artery, making more room for blood flow.
