STABLE ANGINA
|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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