STABLE ANGINA - University of Toronto



|STABLE ANGINA |

|Symptoms |Signs of CAD and CSA |

|pain in anterior chest, left upper arm,|ischemia detected by ECG (normal in 50%|

|left lower arm, neck |CSA pts) |

|tightness, pressure on chest |( HR or BP |

|burning sensation |valvular disease |

|SOB |pulmonary edema |

|weakness |abdominal aortic aneurysm |

|arrhythmia |peripheral vascular vascular disease |

|dizziness |cardiomegaly |

|palpitations |heart failure |

|asymptomatic (**diabetics) | |

*** in CSA, sx are relieved with rest or NTG (45 sec – 5 mins)

Definition (Typical Angina)

- substernal chest discomfort with characteristic quality and duration

- provoked by exertion or emotional stress

- relieved by rest or NTG

***atypical = 2 of above criteria; noncardiac CP = 1

Pathophysiology

- chronic stable angina (CSA) is initial presentation of ischemic ( disease

- ischemia results from fixed atherosclerotic plaque, coronary artery vasospasm, or both

- plaques ( narrowing of coronary arteries and gradually occlude vessel ( imbalance b/w O2 supply and demand

- does not occur at rest; artery adequately supply (

Determinants of Myocardial O2 Demand

1. Heart rate

2. Contractility

3. Intramyocardial wall tension during systole (BP)

** exercise/stress causes ( in these parameters

** tachycardia ( diastolic filling time ( ( blood flow to coronary arteries ( ischemia

Risk Factors

|Modifiable |Non-Modifiable |

|age (male>45; female>55) |smoking |

|premature menopause w/out HRT |HTN |

|gender (male, postmenopausal women) |( total cholesterol |

|family history |( HDL cholesterol |

| |DM |

Differential Diagnosis (Other causes of CP)

|pericarditis |pleuritis |sternoclavicular arthritis|

|PE |cholecystitis |rib fracture |

|pneumonia |herpes zoster |biliary colic |

|GERD |PUD |anxiety disorder |

|pleuritis |pancreatitis |depression |

|esophagitis |fibrositis | |

Precipitating Conditions

|( O2 Demand |( O2 Supply |

|hyperthermia |anemia |

|hyperthyroidism |pneumonia |

|cocain use |asthma/COPD |

|HTN |pulmonary HTN |

|anxiety |sleep apnea |

|hypertrophic cardiomyopathy |interstitial pulmonary fibrosis |

|aortic stenosis |sickle cell disease/polycythemia |

|dilated cardiomyopathy |leukemia/thrombocytosis |

|tachycardia |aortic stenosis |

| |cocaine use |

Diagnosis

|History of anginal sx |Lab Tests |

|quality, severity |to assess risk factors |

|location, radiation |fasting glucose – diabetes |

|precipitating, relieving factors |Hgb – anemia |

|effect of NTG |fasting lipid – dyslipidemia |

| |thyroid function - hyperthyroidism |

| |exercise tolerance test |

CCS Classification System (Grading of AP)

|Class |Description |

|I |sx with strenuous, prolonged work |

|II |slight limitation on physical activity |

|III |marked limitation on physical activity |

|IV |sx at rest |

Goals of Therapy

- ( symptoms

- ( exercise tolerance

- tx other conditions that may worsen angina

- slow disease progression by modifying RFs

- prevent complications (MI, death)

Initial Treatment

A ( ASA and antianginal tx

B ( (-blocker and BP

C ( cigarette smoking and cholesterol

D ( diet and diabetes

E ( exercise and education

Non-pharmacological Options

1. Cholesterol control

2. BP control

3. Smoking cessation

4. Exercise

Pharmacological Options

- use least amt of treatment necessary to minimize sx enough to allow pts to live their life as they wish

- aimed at reversing pathophysiologic and hemodynamic events leading to angina

Stable Angina

ASA 80 – 325 mg/d

Non-Pharms

NTG – SL tab or spray

Yes Effective No

Yes

HTN

No

Nitrates – PO, transdermal

No

Adequate Response ADD BB or long-acting CCB

Yes

Continue Nitrates Adequate response

No Yes

Combination tx Continue

(BB and CCB

or add nitrate)

Cardiovascular Prophylaxis

ASA

Efficacy

- ( risk of subsequent vascular events by 33%

- should be used in all pts

MOA

- anti-platelet: inhibits COX enzyme and synthesis of thromboxane A2

Dosing

- 80 – 325 mg OD

Side Effects

- GI intolerance, ulceration

- ( risk of bleeding

Drug Interactions

- heparin, warfarin

- other NSAIDs

Clopidogrel (Plavix)

Efficacy

- used in pts who can’t tolerate ASA

- CAPRIE trial showed clopidogrel better than chronic ASA

MOA

- ( plasma fibrinogen and ( RBC deformability

- anti-platelet: prevents ADP-mediated platelet activation

- They inc. O2 supply by preventing narrowing of arteries (prevent thrombus formation)

Dosing

- 75 mg OD ($$ - section 8)

Side Effects

- fewer GI S/E than ASA

- nausea, diarrhea, abdominal cramps

- hemorrhage

- h/a, dizziness, cough

- arthralgia

- rash/itch

Drug Interactions

- heparin. warfarin

- ASA and other NSAIDs

- thrombolytics

Note: warfarin is effective but involves too many SE, DI, and requires monitoring.

ACE INHIBITORS

Efficacy

- used in pts with CHF and post-MI LV dysfunction

- HOPE trial showed ( coronary events by 22%

- recommended for pts > 55 y.o. with stable ischemic ( disease

- not effective for symptomatic relief.

- Ramipril has the most evidence.

MOA

- inhibits conversion AT-I ( AT-II

- ( vasoconstriction, ( aldosterone/NE release

- ( degradation of bradykinin (vasodilation)

Dosing

- OD – BID ($$-$$$)

Side Effects

- cough

- hypotension; dizziness

- angioedema (rare but fatal)

- rash

- altered taste

- ( K, ( SCr, ( glucose

Drug Interactions

- ( proteinuria: antiarrhythmics, allopurinol, steroids

- ( hyperkalemia: K-sparing diuretics, K supplements

- lithium

- antacids

Acute Therapy/Short-Term Prophylaxis

Nitroglycerin (NTG)

Efficacy

- sx relief only; but no pain relief

MOA

- rapid systemic and coronary vasodilation (onset ~ 1min)

- ( preload and afterload

- ( O2 supply; ( O2 demand

Dosing

- SL is tx of choice (avoids 1st-pass metabolism)

- take 1 dose at onset of sx; if sx not relieved w/in 5 mins, 2nd dose may be used, and likewise for 3rd

- if sx still not relieved after 3 doses or w/in 15 mins, go to ER

Side Effects

- (BP, (HR, dizziness, h/a, lightheadedness, flushing. Concern with tolerance. Over time, drug does not work as well. Need 10-12 hour nitrate free interval.

Drug Interactions

- sildenafil

Isosorbide Dinitrate (ISDN)

Efficacy

- relieve acute sx with ( duration (60 mins), slower onset

MOA - same as NTG

Dosing

- SL preferred (same sig as NTG spray/tab)

- PO – extensive 1st-pass metabolism (( doses needed)

- TID taken on QID schedule (to ( tolerance)

Side Effects

- (BP, (HR, dizziness, h/a

Drug Interactions

- other nitrates

- sildenafil

Long-Term Prophylaxis – Monotherapy

- started when pt has regular sx or when sx causing ( activity

(-Blockers

Efficacy

- 1st line tx (80 – 90% pts improved anginal sx)

- the only tx shown to affect CAD mortality

- cardioprotective, antiHTN effects

- ideal for pts with concomitant HTN, ( resting HR, supraventricular tachycardia, atrial fibrillation, post-MI angina, stable CHF

MOA

- ( HR, BP, contractility ( ( O2 requirements and less work for the heart.

- They mostly affect demand (not much of an effect on supply)

- ( diastolic filling time ( ( coronary blood flow

Classes

1. Cardioselective (B2-selective)

- atenolol, metoprolol, acebutolol, bisoprolol, betaxolol

2. ISA

acebutolol, carteolol, penbutolol, pindolol. In Stable Angina it is OK to use ISA beta-blockers.

Dosing

- OD – BID ($)

Side Effects

- lethargy, fatigue

- bronchospasm

- bradycardia; hypotension

- sleep disorders

Contraindications

- severe asthma

- severe vascular disease

- Raynaud’s phenomenon

- sinus bradycardia, ( block, cardiogenic shock

- caution in CHF, DM (masks hypoglycemia except sweating), COPD

- ( HR (synergistic) w/ CCB (verapamil, diltiazem), amiodarone, digoxin

Monitoring

- BB dosage – titrated to achieve resting HR of 50 – 60 bpm

- do NOT stop BB abruptly (hyperadrenergic state); taper over 3-4 weeks

Calcium Channel Blockers

Efficacy

- verapamil is 1st choice in pts who can’t tolerate BB

- as effective as other tx when used as monotherapy

- heterogeneous group of agents which differ from each other in MOA and conformation

- but all CCBs equally effective

MOA

- ( Ca entry into smooth muscles ( coronary and peripheral vasodilation

- dihydropyridines – potent vasodilators of peripheral and coronary arteries. No HR lowering effects.

- non-dihydropyridines – moderately potent arterial vasodilators; directly ( AV nodal conduction and have negative chronotropic (HR) and inotropic (contractility) actions

Dosing

- BID – QID ($$$)

Side Effects

- hypotension

- flushing

- h/a, edema

- constipation (especially with Verapamil)

Drug Interactions

- BB, digoxin, amiodarone

- P450 interaction (i.e. cimetidine, rifampin, phenobarbital, digoxin, cyclosporine)

Contraindications

- avoid non-dihydropyridines in pts with conduction disorders or LV dysfunction

- amlodipine is the only one safe in CHF

Nitroglycerin

Efficacy

- topical, oral, transdermal products to ( sx and ( exercise duration

MOA

- same as NTG above

Dosing

- patch – on in am, off in pm

- ISDN – take TID on QID schedule (duration 4-6 hrs)

- ISMN – OD – BID

- isosorbide-5-mononitrate is active metabolite of ISDN

- cannot be used x 24 hrs (nitrate-free 12 hrs to ( tolerance); therefore usually combined with BB or CCB

Side Effects

- same as NTG above

Long-term Prophylaxis – Combination Therapy

- always try monotherapy with alternate agents before trying combination therapy

- little data to support combination

- caution if combining 2 rate-limiting agents (e.g. BB and verapamil) or 2 agents with additive antiHTN effects

• dihydropyridine/nitrate + BB (BB ( reflex tachycardia)

• nitrate + verapamil (verapamil blunts NTG-induced tachycardia)

• CCB + nitrate (if BB contraindicated)

- revascularization procedures (PTCA and CABG) should be considered if pt fails to respond to tx

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