Pharm II: antithrombotics for afib and ischemic stroke

white thrombus

platelet rich

arterial

atherosclerosis

red thrombus

fibrin and RBC rich

veins

DVT/PE

TXA2 (thromboxane)

promotes platelet activation/vasoconstriction

ADP

promotes platelet activation

5-HT

promotes platelet aggregation/vasoconstriction

GP IIb/IIIa

Platelet receptor that binds fibrinogen which is necessary for platelet aggregation

what are the targets for antiplatelet drug therapy?

TXA2 - aspirin

ADP - clopidogrel

GP IIb/IIIa

unfractionated heparin MOA

binds to antithrombin and inhibits several factors

indications unfractionated heparin

- during ACS stenting

- during cardioversion for afib

- VTE prophylaxis/treatment

administration unfractionated heparin

- continuous infusion ACS and warfarin bridging

- subcutaneous VTE prophylaxis

monitoring heparin

aPTT 60-80 seconds

adverse effects heparin

bleeding

HIT

heparin induced thrombocytopenia

antibody-mediated adverse effect of heparin, strongly associated with thrombosis

monitoring for HIT

- Platelets fall > 50% from baseline with nadir > 20,000

- Platelets start to fall on day 5-10 of therapy

- Thrombosis occurs while on heparin

- Rule out other causes of thrombocytopenia

treatment HIT

- stop heparin

- initiate fondaparinux (direct thrombin inhibitor)

- DO NOT give warfarin/DOAC to pt with HIT until platelets return to normal

low molecular weight heparin

enoxaparin

LMWH MOA

inhibit factor Xa > IIa

administration LMWH

subcutaneous

indications for LMWH

ACS

warfarin bridging (afib)

VTE treatment/prophylaxis

monitoring LMWH

- not routinely done, anti-XA level

- reduce frequency in renal impairment, not used in acute kidney failure

adverse effects LMWH

bleeding, HIT (rare)

how do we break apart clots?

fibrinolytics

fibrinolytics MOA

convert plasminogen to plasmin to break up fibrin

types of fibrinolytics

t-PA (tissue type plasminogen activator)

alteplase

when to use antithrombotics for afib/flutter

- prevents PE/stroke and systemic embolism

- decide tx based on stroke risk, bleeding risk, pt preferences and characteristics

which classes are best for antithrombin tx in afib/aflutter

anticoagulant > antiplatelet > nothing

how to determine stroke risk in afib

CHA2DS2-VASc score

CHA2DS-VASc score components

CHF/LV dysfunction

hypertension

age >/= 75

DM

Stroke

vascular disease

age 65-74

sex (female)

CHADSVASC treatment recommendations

- 0 (male) or 1 (female): none

- 1 (male) consider anticoag

- 2 or greater: need anticoag

HAS-BLED score

- Assesses risk of bleeding prior to starting anticoagulants

- ONLY validated for warfarin

- >3 = high risk

which antithrombotic is used in afib/flutter with mechanical heart valves

warfarin

which antithrombotic is used in afib/flutter with severe kidney dysfunction

warfarin

dabigatran MOA

direct thrombin inhibitor

dabigatran stroke risk

reduces stroke risk > VKA

risks dabigatran

increase risk of GI bleed and MI

apixaban MOA

direct factor Xa inhibitor

rivaroxaban MOA

direct factor Xa inhibitor

patient preferences that may influence choice of antithrombotic

- regular INR monitoring

- inconsistent diets

- cost and insurance coverage

- drug-drug interactions

- difficulty remembering doses

stroke types

ischemic and hemorrhagic

hemorrhagic stroke

occurs when a blood vessel in the brain leaks or ruptures; also known as a bleed

ischemic stroke

a type of stroke that occurs when the flow of blood to the brain is blocked via clots or spasm

goals of stroke therapy

- reduce neurologic injury to prevent mortality and long term disability

- prevent stroke recurrence

intravenous t-PA for ischemic stroke dosing

0.9 mg/kg over 1 hour with 10% given as initial bolus over 1 minute

timing of intravenous t-PA

- give within 3 hours of stroke signs to have greatest mortality, morbidity, and recovery benefit

- given w/in 3-4.5 hrs to improve morbidity/recovery

intravenous tenecteplase for ischemic stroke

not FDA approved for stroke, but becoming more often used

when to start antithrombins after thrombolytic therapy

wait 24 hours

stroke treatment protocol

1. activate stroke team

2. treat as early as possible w/in 4.5 hrs

3. CT scan to r/o hemorrhage

4. meet inclusion/exclusion criteria thrombolytic

5. administer thrombolytic

6. avoid all antithrombotics for 24 hrs

7. monitor pt closely for BP, response, hemorrhage

exclusion criteria for stroke medications

active internal bleeding

major surgery/severe trauma w/in 14 days

SBP> 185 mmHg, DBP>110 mmHg

age >80 years

current tx with oral anticoags

statins for stroke prevention

- in pts with presumed atherosclerotic origin of stroke

- high intensity recommended

BP reduction for stroke prevention

goal BP <140/90

CCBs/ACEi/HCTZ > BB

antithrombotic prevention for non-cardioembolic stroke

aspirin, clopidogrel, aspirin/dipyridamole

antithrombotic prevention for cardioembolic stroke

anticoagulation with DOAC/warfarin

dipyridamole MOA

ADP inhibitor

some antiplatelet, some vasodilation

P2Y12 inhibitors in stroke

- can only use clopidogrel

- DAPT increases bleeding risks