STABLE ANGINA



STROKE & TIA | |

|Signs |Symptoms |

|no specific signs but ↑ |speech difficulties (temporary loss, or trouble |

|BP/glucose levels are |understanding speech) |

|“indirect” signs |sudden blindness in one eye |

| |diplopia |

|Note: neurologic |headache (sudden/severe) |

|manifestations differ |seizure |

|depending on: |unsteadiness or sudden falls |

|1) stroke type, |sudden weakness, numbness and/or tingling of the face,|

|2) location of insult |arms or leg (may be transient) |

|(area of brain affected),|hemiplegia (facial/body paralysis of one side of body,|

|3) extent of ischemia, |opposite side of lesion) |

|infarct or hemorrhage |abrupt personality changes (confusion, disorientation)|

| |difficulty swallowing |

| |*these sx often occur early in the morning or at rest |

|Left-Brain Injury: |Right-Brain Injury |

|affects speech, right hand, |affects left hand, music, artistic |

|reasoning, # skills, written |abilities, creativity, insight, spatial |

|language |tasks, perception |

Definitions

Stroke ( syndrome caused by the disruption of blood flow to the brain resulting in sudden onset of a focal neurological deficit that persists for at least 24 hours

TIA ( episode of focal ischemic neurologic deficit lasting < 24 hrs (usually 5-10 minutes); may have the same sx of a stroke; reversible, temporary, no permanent damage; due to a 2º clot

Diagnosis

• CT Scan ( confirms ischemic stroke

• dx of TIA is difficult b/c it is over before pt can be examined

• usu. based on patient recollection of event

Pathophysiology

|Ischemic Stroke (85%) |Hemorrhagic Stroke (15%) |

|lasts 5-10 mins |lasts >1 hr |

|largely caused by either: |escape of blood from a ruptured |

|a) atherosclerosis or thrombosis of |cerebral vessel to surrounding brain |

|cerebral vessels (carotid arteries) ( |tissue ( mass formation ( brain tissue |

|can occur while sleeping or after |is compressed/displaced ( impaired |

|rising |brain function |

|b) cerebral embolism b/c clot, plaque |BLEED |

|or platelet aggregate blocks an artery | |

|( occurs while pt is awake | |

|CLOT | |

Cerebro Vascular Disease (80%)

Infarction (85%)

Cardiogenic Embolism (15%)

Stroke

Brain tissue & Subarachnoid hemorrhage (15%)

• intracranial atherosclerosis (20%)

• carotid plaque with arteriogenic emboli (60%)

• cardiogenic emboli (20%) of which AF (10%)

Similar Signs & Sx

|Drug-Related |Disease-Related |

|oral contraceptives |tumor/trauma to the brain |

|illicit drug use (cocaine, heroin, |Multiple Sclerosis |

|amphetamines, LSD, PCP, etc.) |seizure disorder |

|ASA |electrolyte abnormalities |

|antihypertensives |diabetes (neuropathies) |

Risk Factors

|Non-Modifiable |Modifiable |

|age (risk doubles > 55 yrs) |HTN (a factor in 70% of strokes)* |

|♂ |diabetes |

|family hx |heart disease (↑ risk 2x) |

|Blacks/Asians/ Hispanics |AF |

|Sickle cell disease (clumps RBC, |dyslipidemia |

|restricts blood flow) |mitral stenosis |

|prior stroke/ TIA* |left atrial enlargement |

| |structural abnormalities |

| |MI |

| |migraine (due to VC) ??? |

| |fibrinogen/( elevated hematocrit |

| |lifestyle factors |

| |alcohol |

| |diet |

| |smoking (↑ risk 2-3x) |

| |obesity |

| |physical inactivity |

| |acute triggers – emotional stress |

| |illicit drug use |

Risk Classification – Framingham Profile (( RF (stroke)

• systolic BP

• serum cholesterol

• glucose intolerance

• cigarette smoking

• LVH

Need to Treat?

• yes

• TIAs often precede ischemic stroke; if untreated, may develop stroke w/in 5 yrs

• greatest risk of stroke is w/in first few wks of TIA; 20% w/i 1st month; 50% w/i 1 year

• poorest prognosis with intracranial hemorrhage

Treatment Principles

elimination/management of RF is most important aspect of plan when RF occur in combo, tx should be initiated aggressively

management of HTN is essential

every pt who has had stroke/TIA need to receive anti-platelet as 2º prevention unless CI

Stroke Patients may need…

• snap caps

• larger print on labels

• compliance aids

• alternate dosage form (if having trouble swallowing)

Counseling

• educate pt - most patients unaware of stroke warning signs and are unaware that they have RFs that ( their risk for stroke; ( # of TIA = ( risk of stroke

• regular BP check-ups, low-fat diet, smoking cessation, regular exercise, moderate alcohol consumption

• communication – use Y/N questions; pt may have visual field defects and/or impaired judgment

Pharmacological Options for Ischemic Stroke

Anti-Platelet therapy = prevents platelet aggregation and vasoconstriction

1) ASA – 1st Line

Efficacy

• 1º prevention – no evidence showing ASA is useful; trials showed ( risk of hemorrhagic stroke ( benefit DOES NOT outweigh risk ( do not use ASA UNTIL pt experiences a TIA or stroke

• 2º prevention – clinical benefit seen in low doses; no significant improvement with ↑ doses; ↓ risk of stroke & death by 31%

Evidence

• SALT Trial – 75 mg/d ASA vs. placebo (for every 2 people Tx w/ ASA for 2.5 yrs, there was a clinical benefit ( good to take after TIA)

• UKTIA Trial – 1200 mg/d vs 325 mg/d ASA ( higher doses ( SE but same benefit w/ high and low dose

MOA: irreversibly inhibits platelet COX ( inhibits TXA2 (VC and platelet aggregation inducer)

Onset: minutes (if not EC); max platelet effect in a few days

Dosing:81 mg OD not covered by ODB(use 325 mg OD but take every other day (lowest effective dose is 75 mg OD); chew non-EC for faster onset

SE: GI bleed, GI upset, thrombocytopenia (rare), allergy

DI:anticoagulants (( bleed), anti-platelets (( bleed), alcohol (( bleed), NSAIDS (( risk of GI upset), corticosteroids, ACEI, diuretics, βB, MTX, uricosuric agents (probenecid, sulfinpyrazone); hypoglycemics & phenytoin (( ASA levels);

phenobarbital (( ASA levels)

CI: hypersensitivity, NSAID allergy, active PUD, hemophilia, active bleeding, not for children or those with viral infections (risk of Reye’s syndrome)

Cost:$

2) ASA + dipyridamole (Aggrenox®)

Efficacy

ESPS –1 - combo (vs placebo) significantly MORE effective in preventing stroke (fatal/nonfatal), death, and all end points combined

• ESPS –2 - ASA vs dipyridamole vs combo vs placebo; effects of combo are additive and more effective than either agent given alone, however does not ( severity of of recurrent strokes

• monotherapy w/ dipyridamole ( no use in stroke Pt

MOA: not well understood; may (1) ( [cAMP] by inhibiting adenosine uptake into platelets( inhibit platelet aggregation (2) inhibit cGMP phosphodiesterase ( inhibit platelet aggregation/ activation (3) stimulate prostacyclin synthesis (inhibits platelet aggregation)

Dosing: dipyridamole ER 200 mg + ASA 25 mg BID

Onset: ER few days to max effect

SE: GI (dyspepsia, N/D), h/a, dizziness, serious bleeding events. (risk of bleeding is similar to that of ASA alone)

DI w/ Dipyridamole: adneosine cholinesterase inhibitors

Cost: $1.50/day LU coverage by ODB (2º prevention)

3) clopidogrel (Plavix®)

Use: 2nd line for pts who are intolerant to ASA; ASA + Plavix® can be used after stent surgery

Efficacy

• CAPRIE Trial – 75 mg/d vs ASA 325 mg/d ( clopidogrel more effective than ASA b/c there was a RRR of 9.4% in ischemic stroke, MI or vascular death

• 2º Prevention – for pts who are high-risk; further studies to evaluate effect on risk of stroke

MOA: thienopyridine agent inhibits ADP-induced platelet aggregation (ADP induces fibrinogen binding to platelets)

Dosing: 75 mg OD

Onset: 1-2 hrs, lag time of 3-7 d for platelet effect (delayed compared to ASA)

SE: most common is rash & diarrhea, less GI than ASA, rare: thrombocytopenia

DI: no major DI’s, other antiplatelets (but ASA and Plavix® can be combined b/c different MOA), NSAIDs, thrombolytics, theoretically CYP 2C9 inhibitors (but not documented)

CI: bleeding, hemorrhage

Cost: $3/day – Section 8 Coverage

4) ticlopidine (Ticlid®)

Use: 3rd Line - failure to ASA tx, or intolerant/allergic to ASA

Efficacy

TASS Study – 250 mg BID vs ASA 650 mg BID ( Ticlid® had a 21% greater RRR for stroke than ASA 650 mg BID ( BETTER than ASA for stroke prevention

CATS Trial – Ticlid® vs placebo - ( RR of stroke, MI, vascular death by 30% (high risk stroke pts w/ moderate-severe stroke).

CATS looked at higher risk pts than those in ASA studies

less potent that Plavix® (prodrug)

MOA: same as Plavix

Onset: w/i 6 hrs, platelet effect at 4 days, max effect in 8-11 d

Dosing: 250 mg BID with FOOD

SE: most common is rash & diarrhea; neutropenia and thrombocytopenia (2% - more common than other drugs)

DI: dig, theophylline; more DI’s than Plavix® (although same MOA) b/c excreted renally

CI: liver impairment, gastric bleed, neutropenia, thromboctopenia

Cost: $0.70/tab

Anti-Coagulation (Warfarin)

Use: pts who remain symptomatic w/ TIA on optimal platelet tx who do not have surgical disease

Evidence: no evidence that these are better than anti-platelets in preventing TIA/stroke; trials show no diff b/t tx and control in incidence of recurrent stroke or death; use in stroke is associated with ↑ risk for hemorrhagic complications; long term anti-coagulation ( risk of stroke for pts who previously had MI

Anti-Thrombolytic

Tissue Plasminogen Activator (t-PA)

Use: 3 hrs, uncontrolled HTN, oral anti-coagulants, heparin w/in 48 hrs

Dosing: IV 0.9 mg/kg (max 90 mg) over 1 hour

Cost: expensive

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