Antiplatelet drugs, mechanism of action (MOA), indication, highlights, duration of action, and reversal agents
Antiplatelet
Drug
MOA
Use
Aspirin PO
COX-1:
arachidonic acid
pathway
inhibitor
Clopidogrel
(Plavix) PO
Ticagrelor
(Brilinta)
PO
P2Y12: ADP
pathway
inhibitor
ASC medically
management or
PCI; ischemic
stroke/transient
ischemic stroke,
PAD
ASC medically
management or
PCI; PAD
(Clopidogrel)
Prasugrel
(Effient) PO
Tirofiban
(Aggrastat)
IV
They are
interchangeable
in some cases,
please ask your
pharmacists for
dosing
conversion.
Glycoprotein
(GP) IIb/IIIa
receptor
antagonist
Before PCI, in
high risk of
thrombus
Highlights
Return of
normal platelet
function
Bleeding & Reversal
agent
325 mg non-enteric coated one time dose for angina, and the sequent
dose (maintenance dose) should be 81 mg, including in Dual Antiplatelet
Therapy (DAPT) with P2Y12 post PCI
7-10 days
Stop the medication
And
Desmopressin +/- platelet
infusion
300mg – 600 mg once as loading dose, and followed by 75 mg daily the
next day
180 mg once prior to PCI in combination with Aspirin 81 mg and a parental
anticoagulant, followed by maintenance dose 90 mg twice a day beginning
12 hours after the loading dose
Avoid concurrent use with maintenance dose of Aspirin > 100 mg
60 mg once before PCI in with Aspirin and IV anticoagulant, followed by
maintenance dose of 10 mg daily the next day with Aspirin 81 mg. If < 60
kg, maintenance dose 5 mg daily for 12 months unless high risk of bleeding
and continue aspirin 81 mg indefinitely or alternative.
Contraindicated: ≥ 75 years old, active bleeding, history of TIA or stroke.
Do not initiate therapy if likely undergo urgent CABG, when possible
discontinue ≥ 7 days
A loading dose of 25 mcg/kg (referred to as the high-bolus dose) over five
minutes or less, and followed by a continuous infusion of 0.15 mcg/kg/min
for up to 18 hours
If CrCl < 60 mL/min- reduce the dose by 50%
If CABG is planned, discontinue ≥4 hours before surgery
5-7 days
3-5 days
5-7 days
4-8 hours
Discontinuation of antiplatelet
agents must be weighed
against the risk of arterial
thrombosis (i.e. if a patient has
a bare metal or drug eluting
stent placed within the past 13 months, respectively).
Premature cessation of dual
antiplatelet therapy can lead
to stent thrombosis which can
be potentially fatal.
Stop the medication, short
half-life, no reversal agent
needed
Anticoagulant
Drugs
MOA
Use
Heparin IV
Inhibit
thrombin
and some
factor Xa
ACS, PE, DVT,
Afib
DVT prophylaxis
ACS, DVT, PE,
Afib,
DVT prophylaxis
Heparin SQ
Enoxaparin
(Lovenox) SQ
(LMWH)
Argatroban IV
Bivalirudin
(Angiomax) IV
Direct
thrombin
inhibitor
Dabigatran
(Pradaxa) PO
Direct
thrombin
inhibitor
(PO Only)
Apixaban
(Eliquis) PO
Inhibits
platelet
activation
and fibrin
clot
formation
via factor
Xa
Factor Xa
inhibitior
Rivaroxaban
(Xarelto) PO
Edoxaban
(Savaysa) PO
ACS, PE, DVT,
Afib
Notes
DOA
Reversal agent
Nomogram - Goal of aPTT is the same
•
Low intensity: used in ACS, Afib
•
High intensity (with bolus, achieves the therapeutic level quicker): use in PE and
DVT
•
No nomogram not recommended. May cause extensive bleeding, or not reach
therapeutic level, either can result in patient harm
Preferred agent in Crcl < 10 mg
-Therapeutic dose: 1mg/kg Q24H (CrCl > 30), Q12H (CrCl <30): used in ACS (medical
management, or prior to stent or CABG); PE, DVT, Afib
-DVT prophylaxis dose: 40 mg (CrCl >30) or 30 mg (CrCl <30) daily
-Can cause HIT, as it is a LMWH. Risk increases with doses over prophylactic doses,
female sex, and duration of therapy over 5 days.
Use in HIT as alternative: start with 0.15 to 0.2 mg/kg/hour adjusted to therapeutic aPTT
4-6 hours
Protamine
12-24
hours
Not reversal needed
PCC4 (Kcentra ®) or Protamine
sulfate
2-4 hours
2–6
hours
Nonmajor bleeding: stop
infusion, no reversal agent
indicated
During PCI: 0.75 mg/kg bolus immediately prior to procedure, followed immediately by
1.75 mg/kg/hour for duration of procedure. May continue at 1.75 mg/kg/hour for up to 4
hours
PE, DVT, Afib
(not for
mechanical
valves)
Afib: 150 mg BID; 75 mg BID in CrCl 15 to 30; CrCl < 15 avoid use
PE, DVT: 150 mg BID with at least 5 days of bridging with anticoagulant; no dose
adjustment; avoid use in CrCl < 30
Afib: 5 mg BID; 2.5 mg BID in if meets two of the factors of Scr > 1.5, age > 80, weight <
60 kg
Afib, VTE, PE
DVT, PE: 10 mg BID x 7 days followed by 5 mg BID (no reduced dose)
Afib: 20 mg with evening meal (food increases the absorption); 15 mg in CrCl < 50 but >
15
PE, DVT: CrCl > 30, no dose adjustment; CrCl 15 to 30 not been studied; CrCl < 15 avoid
use
Patient weight >60kg: 60mg Once Daily
CrCl 15-30: 30mg Once Daily
Patient weight ≤ 60kg: 30mg Once Daily
CrCl >15: Avoid
Nonvalvular Afib with CrCl >95: avoid due to reduced efficacy
1-2 days
in CrCl
>50
mL/min;
3-5 days
in CrCl
<50
2-4 days
Major bleeding:
add PCC4 (Kcentra ®) or
fresh frozen plasma
PCC4 (Kcentra ®)
Andexanet alfa (Andexxa®)
PCC4 (Kcentra ®)
Andexanet alfa (Andexxa®)
1-3 days
10-14
hours
PCC4 (Kcentra ®)
Andexanet alfa (Andexxa®)
Anticoagulants Continued
Fondaparinux
(SC only)
Warfarin
(Coumadin)
PO
Factor Xa
inhibitor
Vitamin K
antagonist
DVT, PE, Afib,
DVT prophylaxis
PE, DVT, Afib
(including
mechanical
valves)
DVT/PE: SUBQ:
patient
<50 kg: 5 mg once daily.
VTE prophylaxis: 2.5 mg once daily, not to be used in
14-17h
PCC4 (Kcentra ®)
Andexanet alfa (Andexxa®)
2-5 days
INR > 10 without bleeding:
hold Warfarin and give
Vitamin K (Phytonadione)
under 50kg. Can be used in HIT
50 to 100 kg: 7.5 mg once daily.
>100 kg: 10 mg once daily.
Warfarin naïve. Initial dose 5 mg once daily for 3 days, and check INR the morning of day
4, adjust the dose based on INR level
Bridging with a parental anticoagulant during initiating of Warfarin until stable INR is
attained in high risk for thromboembolism
Bleeding: add PCC (Kcentra),
or fresh frozen plasma
Summary of Therapy
Therapy
Mono antiplatelet therapy
Dual antiplatelet therapy
Aspirin 81 mg alone
Aspirin 81 mg plus any P2Y12
combination-Dual Antiplatelet
Therapy (DAPT)
Triple antiplatelet therapy -short term
Aspirin + P2Y12 + Glycoprotein (GP)
IIb/IIIa receptor (Tirofiban and
Eptifibatide)
Aspirin with P2Y12 and anticoagulant
in patient with Afib underwent PCI
Triple antithrombotic therapy (dual
antiplatelet with single anticoagulant)
Notes
Secondary Stroke, Myocardial Infarction (MI), Unstable Angina (UA), peripheral artery disease (PAD)
Post PCI -drug eluting (DES) x 1 year, followed
With any of P2Y12, Clopidogrel, Ticagrelor, or
by Aspirin 81 mg or P2Y12 indefinitely
Prasugrel
Medical management of NSTEMI for at least 1
Only with Clopidogrel or Ticagrelor, no Prasugrel
month and up to a year
With DAPT above, consider GP IIb/IIIa in high-risk patients (eg, significant thrombus burden) when PCI is
planned, continue up to 18 to 24 hours
•
•
Only P2Y12 has been studied is Clopidogrel and has lowest bleeding risk among three P2Y12
PPI is recommended but not Esomeprazole or Omeprazole due to decreasing serum active form
of Clopidogrel
o Duration of triple therapy
▪
1 month if low bleeding risk
▪
1 week if high risk of bleeding risk
Drop Aspirin, keep P2Y12 + Anticoagulant
Reference:
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UpToDate. https://www.uptodate.com/contents/aspirin-druginformation?search=aspirin+&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed April 11, 2023.
https://www.uptodate.com/contents/clopidogrel-drug-information?source=auto_suggest&selectedTitle=1~3---1~3---clopi&search=clopidogrel
https://www.uptodate.com/contents/ticagrelor-druginformation?search=ticagrelor&source=search_result&selectedTitle=1~92&usage_type=panel&kp_tab=drug_general&display_rank=1#topicContent. UpToDate.
https://www.uptodate.com/contents/clopidogrel-drug-information?source=auto_suggest&selectedTitle=1~3---1~3---clopi&search=clopidogrel. Accessed April 11, 2023.
https://www.uptodate.com/contents/prasugrel-drug-information?search=prasugrel&source=search_result&selectedTitle=1~65&usage_type=panel&kp_tab=drug_general&display_rank=1
https://www.uptodate.com/contents/tirofiban-drug-information?search=tirofiban&source=search_result&selectedTitle=1~26&usage_type=panel&kp_tab=drug_general&display_rank=1.
UpToDate. https://www.uptodate.com/contents/prasugrel-drug
https://www.uptodate.com/contents/heparin-and-lmw-heparin-dosing-and-adverse-effects?search=heparin%20&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
https://www.uptodate.com/contents/enoxaparin-including-biosimilars-available-in-canada-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---Enoxa&search=enoxaparin#
https://www.uptodate.com/contents/argatroban-drug-information?search=argatroban&source=search_result&selectedTitle=1~42&usage_type=panel&kp_tab=drug_general&display_rank=1
https://www.uptodate.com/contents/apixaban-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---apixaba&search=apixaban. UpToDate.
https://www.uptodate.com/contents/argatroban-drug-information?search=argatroban&source=search_result&selectedTitle=1~42&usage_type=panel&kp_tab=drug_general&display_rank=1.
Accessed April 11, 2023.
https://www.uptodate.com/contents/rivaroxaban-drug-information?search=rivaroxaban&source=search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1
IdaruCIZUmab (Lexi-Drugs) - UpToDate® Lexidrug™ (oclc.org)
Andexanet Alfa (Coagulation Factor Xa [Recombinant], Inactivated) (Lexi-Drugs) - UpToDate® Lexidrug™ (oclc.org)