PATHO/PCT LECTURE 53&54 DUNN (10/11&12) [EXAM 4]

T/F: PCI is inherently thrombogenic

true

what pharmacologic agents suppress thrombogenic effects of PCI

-thrombin generation -->

-platelet activation -->

vessel wall injury inflammation -->

-thrombin generation --> indirect thrombin inhibitor (UFH, LMWH) and direct thrombin inhibitor (bivalirudin)

-platelet activation --> ASA + P2Y12 inhibitors with or without GP IIb/IIIa inhibitors

vessel wall injury inflammation --> high intensity statin

what are the two types of stents

bare metal stent and drug eluting stent

which stent provides more flexibility to stop P2Y12 inhibitor earlier than preferred 12 months if needed

bare metal stent

which of the P2Y12 inhibitors are IV

cangrelor

which P2Y12 inhibitors are irreversible

clopidogrel and prasugrel

which P2Y12 inhibitors are reversible

ticagrelor and cangrelor

what is the LD of clopidogrel for PCI

600mg PO

what is the LD of clopidogrel for fibrinolytics

300mg PO

what is the maintenance dose of clopidogrel (for both PCI or fibrinolytics)

75mg PO QD

how long should clopidogrel be held prior to CABG due to irreversible binding

5-7 days

clopidogrel has ______ time to onset of action and _______ time to peak platelet inhibition

longest, longest

what CYP450 does clopidogrel metabolize through

CYP2C19

what drug interaction with clopidogrel via CYP2C19

omeprazole - PPI

what is BBW for clopidogrel

genetic variation

is clopidogrel safe in stroke

yes

what is LD of prasugrel/effient

60mg

what is maintenance dose of prasugrel/effient

10mg QD

when should the maintenance dose of prasugrel/effient be reduced and what is it reduced to

< 60 kg...5mg QD

T/F: prasugrel used for PLANNED PCI

true

in what patients does prasugrel show greater reduction in ischemic events without an increase in TIMI major bleeding; MI reduction

DM

what is BBW/contraindication for prasugrel

history of stroke/TIA

is prasugrel OK to give if patient likely to undergo CABG

no

when should prasugrel be avoided

≥ 75 years due to increased risk of fatal and intracranial bleeding and uncertain benefit (BBW)

what patient population > 75 is exception to avoiding prasugrel

prior MI or DM

what are potential benefits of prasugrel therapy

quickest PO onset, reduced interpatient variability, greater intensity of platelet inhibition, and limited drug-drug interactions

which P2Y12 has longest CABG hold time of 7 days

prasugrel

what is LD of ticagrelor/brilinta

180mg

what is maintenance dose of ticagrelor/brilinta

90mg BID

T/F: ticagrelor/brilinta can be used in ACS patients undergoing PCI or ischemia guided approach

true

where does ticagrelor fall in bleed risk vs clopidogrel and prasugrel

greater bleed risk vs clopidogrel but less a risk than prasugrel

what are unique side effects of ticagrelor (and cangrelor)

dyspnea, asymptomatic ventricular pauses/bradycardia, and increase in uric acid & SCr

what is BBW of ticagrelor

MD of ASA > 100mg reduce effectiveness of ticagrelor and should be avoided...after initial dose, use with ASA 75-100mg/day

what are potential benefits of ticagrelor

reversible action, greater platelet inhibition, use in CABG, mortality benefit

what are potential harm of ticagrelor

reversible action, bleeding risk, interaction with high dose aspirin, ICH

ticagrelor has potential interactions with ??

CYP3A4 inhibitors/inducers

which PO P2Y12 inhibitor has quickest duration of action and platelet recovery time

ticagrelor

T/F: ticagrelor has increased ICH risk but similar stroke rate to clopidogrel (BBW)

true

unique advantage of IV cangrelor may be in context of what ??

bleeding or transition to CABG

T/F: cangrelor reduces risk of thrombotic events in patients undergoing PCI (for those not being treated with another P2Y12 or GP IIb/IIIa)

true

efficacy is greater with which P2Y12 inhibitors

prasugrel and ticagrelor over clopidogrel

safety concern of increased bleeding risk with which P2Y12 inhibitors

greater with prasugrel (and ticagrelor) over clopidogrel

what P2Y12 inhibitor could be used if any of these:

< 60kg, age ≥ 75 (NSTEMI), history of TIA/stroke and/or at higher bleeding risk, on warfarin

clopidogrel

what P2Y12 inhibitor could be used if any of these:

primary PCI in STEMI (especially if high risk DM or prior MI), age < 75, > 60kg, clopidogrel hyporesponder, no CVA/TIA

prasugrel

what P2Y12 inhibitor could be used if any of these:

unknown coronary anatomy and/or high likelihood of nonurgent CABG, no ICH, clopidogrel hyporesponder, good compliance

ticagrelor

if NSTEMI and going towards invasive strategy, what P2Y12 to choose from

clopidogrel or ticagrelor

if STEMI and going for invasive strategy, what P2Y12 to choose from

clopidogrel

what is dose for IV drip of eptifibatide/integrilin

2mcg/kg/min x 18-24hr

what are the three GP IIb/IIIa inhibitors

eptifibatide/integrilin

abciximab/reopro

tirofiban/aggrastat

which GP IIa/IIIb inhibitor has longest plasma half life

eptifibatide/integrilin

what elimination for eptifibatide/integrilin

renal elimination

when do we dose adjust for renal function with eptifibatide/integrilin

CrCl < 50mL/min

what is dose adjustment for eptifibatide/integrilin with CrCl < 50mL/min

1mcg/kg/min x 18-24hr

which GP IIb/IIIa inhibitor has lowest/medium bleeding risk of the three

eptifibatide/integrilin

which GP IIb/IIIa inhibitor of the three is irreversible

abciximab/reopro

which GP IIb/IIIa inhibitor has quickest plasma half life

Abciximab/ReoPro

how is Abciximab/ReoPro eliminated

plasma elimination

which GP IIb/IIIa inhibitor has highest bleeding risk of the three

Abciximab/ReoPro

how is Tirofiban/Aggrastat eliminated

renal elimination (dose adjust for CrCl < 30mL/min)

which GP IIb/IIIa inhibitor has intermediate bleeding risk of the three

Tirofiban/Aggrastat

in what patients are GP IIb/IIIa inhibitors used in

patients with HIGH RISK features such as ischemic EKG changes or positive cardiac enzymes

what GP IIb/IIIa inhibitor should be used in hemodialysis patient

abciximab/reopro

when should GP IIb/IIIa inhibitors be used in unstable angina/NSTEMI

o No pretreatment with P2Y12 inhibitor (and not treated with bivalirudin)

o Large thrombus burden

o HIGH RISK patients in cath lab (ischemic EKG changes or positive cardiac enzymes)

T/F: there is NO reduction of ischemic events and increased bleeding risk with use of GP IIb/IIIa inhibitors upstream (prior to angiography)

true

which GP IIb/IIIa inhibitor can NEVER be used upstream

abciximab/reopro

should ticagrelor be used in fibrinolysis

no

in what two scenarios should prasugrel not be used in

NSTEMI ischemia guided and STEMI fibrinolysis

should GP IIb/IIIa inhibitors be used in NSTEMI ischemia guided or STEMI fibrinolysis

no

what are advantages of UFH therapy

immediate anticoagulation, easy to monitor for efficacy, long clinical use history and physician comfort, easy to d/c due to short acting, reversible with protamine (ONLY one), inexpensive, can be used in renal dysfunction

what are disadvantages of UFH therapy

inconsistent/unpredictable anticoagulant effect, frequency of monitoring, thrombocytopenia, rebound thrombogenicity

what is treatment dose of enoxaparin (LMWH)

1mg/kg SQ q12h

what is renal adjusted dose of enoxaparin (LMWH) if CrCl < 30mL/min

1mg/kg SQ q24h

what are advantages of LMWH therapy

more predictable and sustained anticoagulation, monitoring not necessary, lower risk of HIT, long history of clinical use

what are disadvantages of LMWH therapy

less reversible than UFH, difficult to monitor if needed, renally cleared, longer half life, risk of HIT, increased bleeding risk vs UFH, dosed BID

what is dose for fondaparinux/arixtra

2.5mg SQ q24h

is fondaparinux/arixtra used for PCI by itself? can it be used with fibrinolysis or ischemia guided

not used by itself...yes it can

what are three contraindications for fondaparinux/arixtra

· CrCl < 30mL/min

· Weight < 50kg

· Active bleeding

what are advantages of fondaparinux therapy

similar ischemic events vs enoxaparin, less bleeding risk, mortality benefit, daily dosing, no monitoring

what are disadvantages of fondaparinux therapy

more catheter thrombosis during PCI so must use UFH/bivalirudin during PCI, avoid if CrCl < 30mL/min or weight < 50kg, longer half life

what is MOA of bivalirudin/angiomax

reversible inhibitor of thrombin - both clot bound and circulating

when is bivalirudin/angiomax the DOC

DOC in HIT/heparin allergy + PCIs

does bivalirudin/angiomax cause thrombocytopenia

no

what can bivalirudin/angiomax be monitored with

aPTT

what are advantages of bivalirudin/angiomax therapy

similar ischemic events, less bleeding risk, eliminates need for GP IIb/IIIa inhibitor, ease of use, good option if high bleeding risk or thrombocytopenia, short acting (shortest half life)

what are disadvantages of bivalirudin/angiomax therapy

expensive, efficacy may depend on pretreatment with clopidogrel, limited date in renal insufficiency, increased ischemic events in high risk patients (positive troponin)