Download A4 Stable Angina

STABLE ANGINA
Symptoms
Signs of CAD and CSA
- pain in anterior chest, left
- ischemia detected by ECG
(normal in 50% CSA pts)
upper arm, left lower arm,
neck
-  HR or BP
- tightness, pressure on chest - valvular disease
- burning sensation
- pulmonary edema
- SOB
- abdominal aortic aneurysm
- weakness
- peripheral vascular vascular
- arrhythmia
disease
- dizziness
- cardiomegaly
- palpitations
- heart failure
- asymptomatic (**diabetics)
*** in CSA, sx are relieved with rest or NTG (45 sec – 5 mins)
Diagnosis
History of anginal sx
- quality, severity
- location, radiation
- precipitating, relieving
factors
- effect of NTG
Lab Tests
to assess risk factors
fasting glucose – diabetes
Hgb – anemia
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
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
Goals of Therapy
-  symptoms
-  exercise tolerance
- tx other conditions that may worsen angina
- slow disease progression by modifying RFs
- prevent complications (MI, death)
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 
Initial Treatment
A  ASA and antianginal tx
B  -blocker and BP
C  cigarette smoking and cholesterol
D  diet and diabetes
E  exercise and education
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
- age (male>45; female>55)
- premature menopause w/out HRT
- gender (male, postmenopausal
women)
- family history
-
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
Non-Modifiable
smoking
HTN
 total cholesterol
 HDL cholesterol
DM
Differential Diagnosis (Other causes of CP)
- pericarditis
- pleuritis
- PE
- cholecystitis
- pneumonia
- herpes zoster
- GERD
- PUD
- pleuritis
- pancreatitis
- esophagitis
- fibrositis
-
sternoclavicular
arthritis
rib fracture
biliary colic
anxiety disorder
depression
Stable Angina
ASA 80 – 325 mg/d
Non-Pharms
NTG – SL tab or spray
Yes
Effective
No
Yes
HTN
No
Precipitating Conditions
 O2 Demand
-
hyperthermia
hyperthyroidism
cocain use
HTN
anxiety
hypertrophic cardiomyopathy
aortic stenosis
dilated cardiomyopathy
tachycardia
Ada Seto – October 2002
 O2 Supply
-
anemia
pneumonia
asthma/COPD
pulmonary HTN
sleep apnea
interstitial pulmonary fibrosis
sickle cell disease/polycythemia
leukemia/thrombocytosis
aortic stenosis
cocaine use
Nitrates – PO, transdermal
No
Adequate Response
Yes
Continue Nitrates
ADD
BB or long-acting CCB
Adequate response
No
Combination tx
(BB and CCB
or add nitrate)
Yes
Continue
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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
Ada Seto – October 2002
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, 2 nd
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
-2-
- 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
 CCB + nitrate (if BB contraindicated)
- revascularization procedures (PTCA and CABG) should be
considered if pt fails to respond to tx
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)
Ada Seto – October 2002
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