PCT V acute coronary syndrome

- recurrent MI
- sudden cardiac death
- HF
- stroke

morbidity of acute coronary syndromes

- endothelial dysfunction
- inflammation
- fatty streak formation

etiology of coronary artery syndrome (plaque formation in coronary artery)

- collagen, tissue factor exposure --\> platelet activation and aggregation
- extrinsic coagulation cascade activation --\> thrombin production
- clot stabilization

pathophysiology of acute coronary artery syndrome

- midline anterior chest pressure (elephant sitting on my chest) (classic symptom)
- radiating jaw/neck/back/arm pain, nausea, diaphoresis, shortness of breath
- can have atypical symptoms that do not include the classic anginal pain

subjective findings in ACS

- 12 lead EKG
- ST elevation for STEMI
- ST depression for NSTEMI
- T wave inversion for NSTEMI

objective findings in ACS

- ACS suspected if there is a rise and fall of values
- NSTEMI and STEMI have positive biomarkers

cardiac enzymes/biomarkers (troponin I/T, hs-cTn) in ACS

- morphine 2-4mg IV (try this first before NTG)
- oxygen is O2 sats < 90% or features for hypoxemia are present
- aspirin 162-325mg for 1 dose (can use clopidogrel is aspirin intolerant) than maintenance dose of 81mg
- nitroglycerin 0.4mg tablets (last line)

ACS initial treatment as soon as arriving at hospital

- obtain 12 lead EKG and initial biomarkers, then...
- thienopyridines (P2Y12 inhibitors)
- heparin (anticoagulation)
- renin/angiotensin inhibition
- beta blockers
- intervention
- statins
THROMBINSS

ACS initial treatment before patient leaves the hospital

oxygen

which initial management of ACS has no benefit unless there is low O2 saturation

morphine and nitroglycerin

which initial management of ACS does not improve mortality and is only used for chest pain and symptomatic relief

- primary percutaneous coronary intervention (PCI)
\--- STEMI reperfusion therapy of choice: balloon angioplasty, bare-metal stent (BMS) or drug-eluting stent (DES)
\--- recommended reperfusion therapy for high-risk NSTEMI patients

non-pharmacologic ACS treatment

- risk based on scoring systems (TIMI and GRACE
- refractory angina
- acute heart failure
- cardiogenic shock
- arrhythmias

what type of NSTEMI patients are are high risk and should consider reperfusion therapy

reperfusion

which has a lower mortality rate: reperfusion therapy or fibrinolytics

- aspirin (combo therapy with P2Y12)
- P2Y12 inhibitors (combo therapy with aspirin)
- glycoprotein IIb, IIIa inhibitors (high risk patients only)

anti-platelet agents for ACS

- unfractionated heparin
- low molecular weight heparin
- fondaparinux (not for PCI treated patients)
- bivalirudin (not used in ischemia-guided strategy)

anticoagulant agents for ACS

glycoprotein IIb, IIIa inhibitors

which antiplatelet agent should be used for high risk patients only with ACS

fondaparinux

which anticoagulant agent for ACS should not be used in PCI treated patients

bivalirudin

which anticoagulant agent for ACS should not be used in ischemia-guided strategy

- clopidogrel
- prasugrel
- ticagrelor

P2Y12 antagonist examples

- aspirin +
- clopidogrel/prasugrel/ticagrelor

early invasive NSTEMI antiplatelet therapy

- aspirin +
- clopidogrel/ticagrelor

ischemia guided NSTEMI antiplatelet therapy

- aspirin +
- clopidogrel/prasugrel/ticagrelor

primary PCI STEMI antiplatelet therapy

- aspirin +
- clopidogrel

fibrinolytic STEMI antiplatelet therapy

CYP2C19
guidelines currently do not recommend genotyping to assess clopidogrel responsiveness

response to clopidogrel can be enhanced OR blunted if what genetic polymorphism is present

- ischemia-guided NSTEMI ACS
- STEMI patients treated with a fibrinolytic
- patient with a history of TIA or stroke

do not use prasugrel in...

caution in low body weight patients or elderly

caution with prasugrel

ticagrelor

reversible P2Y12 inhibitor

don't exceed 100mg/day

with ticagrelor, do not exceed maintenance aspirin doses of...

- bradycardia
- dyspnea

side effects of ticagrelor

- clopidogrel
- prasugrel

which P2Y12 inhibitor is a prodrug

- clopidogrel: 4-6 hours
- prasugrel: 1 hour
- ticagrelor: 30 min

onset of action for clopidogrel, prasugrel and ticagrelor

- clopidogrel: 5-10 days
- prasugrel: 7-10 days
- ticagrelor: 3-5 days

offset of action for clopidogrel, prasugrel, and ticagrelor

cyp2C19

drug-drug interactions with clopidogrel

none

drug-drug interactions with prasugrel

cyp3A4

drug-drug interactions with ticagrelor

clopidogrel: 5 days
prasugrel: 7 days
ticagrelor: 5 days

holding before surgery for how many days?
clopidogrel:
prasugrel:
ticagrelor:

cangrelor

intravenous P2Y12 inhibitor

patient not pre-treated with an oral P2Y12 inhibitorand who are not receiving a GPIIb/IIIa inhibitor

when to consider cangrelor in ACS treatment

false

T/F you can begin clopidogrel or prasugrel before cangrelor infusion is complete

true

T/F you cannot begin clopidogrel or prasugrel until cangrelor infusion is completed

- eptifibatide
- tirofiban

GPIIb/IIIa examples

eptifibatide

do not use which GPIIb/IIIa in hemodialysis patients

6 hours after infusion is discontinued

patient function returns how long after GPIIb/IIIa is discontinued

unfractionated heparin

which anticoagulant does not require a renal adjustment

- unfractionated heparin
- enoxaparin

watch for heparin-induced thrombocytopenia with what medications

enoxaparin

which anticoagulant is not the preferred in STEMI patients receiving primary PCI

patients with CrCl < 30

contraindications for fondaparinux

- fondaparinux
- bivaluridin

which anticoagulant can be used in patients with heparin induced thrombocytopenis history

bivalirudin

which anticoagulant can be used in all PCI-related treatment strategies

- STEMI fibrinolytic
- NSTEMI ischemia-guided strategy

bivalrudin is not recommended for use in...

- STEMI patient
- expected "door to balloon time" of \> 90 min OR expected transfer time to a PCI-capable facility is \> 120 min
- onset of symptoms is < 12 hours and no contraindications

when to consider fibrinolytic therapy

- any prior ICH or stroke of unknown origin
- known structural cerebral vascular lesion
- known malignant intracranial neoplasm
- ischemic stroke within previous 3 months
- suspected or confirmed aortic dissection
- active internal bleeding
- significant closed-head trauma or facial trauma within previous 3 months
- intracranial or intraspinal surgery with previous 2 months
- severe uncontrolled hypertension
- known malignancy or life expectance < 6 months

contraindications with fibrinolytic agents

- alteplase
- reteplase
- tenecteplase
- streptokinase

fibrinolytic agent examples

aspirin + P2Y12 inhibitor

long term management of ACS

rivaroxaban

medication that could be added to clopidogrel + aspirin regimen 1 year post ACS

- LV dilation
- ace inhibitors
- arbs
- beta blockers
- aldosterone antagonists

ACS long term management with ventricular remodeling post-MI

- hemodynamic compromise or heartfailure
- monitor HR and BP

with beta blockers, watch for signs/symptoms of....

- BP
- basic metabolic profile (potassium, serum creatinine)
- cough (ace inhibitors)

adverse effects of ace inhibitors and arbs

adjunctive therapy for patients already on beta blocker and ACE/ARB and have reduced EF and either signs/symptoms of heart failure or diabetes

when to use aldosterone antagonists (spironolactone and eplerenone) in ACS long term management

- hyperkalemia
- renal dysfunction
- gynecomastia (spironolactone)

adverse effects of aldosterone antagonists (spironolactone and eplerenone)

false, can use for post-MI patients even if lipids are well controlled

T/F only use statins in long term management of ACS if post-MI patient's lipids are uncontrolled

true

T/F you can use statins in long term management of ACS in post-MI patients lipids are well controlled

high intensity statins: atorvastatin 40/80mg or rosuvastatin 20/40mg

which statins are preferred for long-term management for ACS

- LFT elevation
- hepatotoxicity
- myalgias

adverse effects of statins

- ezetimibe
- PCSK9 inhibitors (alirocumab)

non-statin lipid lowering therapies

- patients unable to tolerate high intensity statin or
- LDL remains significantly elevated on high intensity statin

when to use non-statin lipid lowering therapies

nitroglycerin

what other medication can be prescribed to patients post-MI

streptokinase

which fibrinolytic agent is not fibrin specific

door to needle time of 30 min

appropriate timing of fibronolytic therapy

- unfractionated heparin

anticoagulants that can be used in all forms and treatment strategies of ACS

- enoxaparin

anticoagulant that can be used in all forms and treatment strategies of ACS except STEMI patients receiving primary PCI

- fondaparinux

anticoagulant that can be used in STEMI + fibronolytic strategy or ischemia-guided NSTE ACS strategy but not PCI

bivalrudin

anticoagulant that can be used in all PCI-related treatment strategies (STEMI--primary PCI, NSTE ACS-early invasive)

should be given concomitantly with fibrinolytic when patient has a STEMI

when should an anticoagulant be considered

- anticoaulation
- P2Y12 inhibitor
- antiplatelet (aspirin)

what medications should be started if patient is on fibrinolytic therapy and has a STEMI

60 units/kg bolus, followed by 12 units/kg/hr (max 1000 units/hr)
48 hours

dose and duration of unfractionated heparin

- normally 1mg/kg every 12 hours
- if STEMI + fibrinolytic: 30mg IV bolus at time of first maintenance dose if < 75 years old
- continue duration for 8 days
check email!

dose and duration of enoxaparin

2.5mg Sq daily for 8 days

dose and duration for fondaparinux

0.75mg/kg bolus, followed by 1.75mg/kg/hr for 4 hours

dose and duration for bivalirudin

minimum: 14 days while continuing aspirin lifelong
want to aim for 12 months, and then just aspirin infinitely

duration of therapy for dual antiplatlet therapy

- ST segment decreases
- T wave inversion
- no ekg changes
- CARDIAC BIOMARKERS ARE NOT POSITIVE

diagnosis characteristics of unstable angina

- ST segment decreases
- T wave inversion
- no ekg changes
- CARDIAC BIOMARKERS ARE POSITIVE

diagnosis characteristics of NSTEMI

- ST elevation \> 1mmin \> 2 leads
- positive cardiac biomarkers

diagnosis characteristics of STEMI

- early invasive therapy (should be considered if TIMI score is around 6-7%)
- ischemia guided therapy (more conservative if TIMI score is around 2%)

treatment strategies for NTEMI

- early invasive therapy (should be considered if TIMI score is around 6-7%)
- ischemia guided therapy (more conservative if TIMI score is around 2%)

treatment strategies for unstable angina

- PCI
- fibriniolytic therapy

treatment strategies for STEMI

current oasis 7

trial that found that low-dose aspirin is not significantly different than high-dose aspirin with respect to CV death, MI or stroke; but there are higher rates of minor bleeding in high dose aspirin arm

loading dose: 300-600mg once
maintenance dose: 75mg daily

dosing for clopidogrel

CURE

trial that discovered that aspirin + clopidogrel significantly decreased CV death, nonfatal MI, and stroke versus aspirin alone

loading dose: 60mg once
maintenance dose: 10mg daily

doing for prasugrel

triton-timi

trial that discovered prasugrel significantly decreases CV death, MI and stroke versus clopidogrel

loading dose: 180mg once
maintenance dose: 90mg BID

dosing for ticagrelor

PLATO

trial that discovered that ticagrelor significantly decreased vascular death, MI and stroke versus clopidogrel

loading dose: 30mcg/kg once
maintenance dose: 4mcg/kg/min

dosing for cangrelor

champion-phoenix

trial that discovered that cangrelor significantly decreased death/MI/revascularization/stent thrombosis vs clopidogrel

with PCI: 180mcg/kg bolus twice, 10 min apart, then infusion 2mcg/kg/min for 18-24 hours
without PCI: 180mcg/kg bolus once, then infusion of 2,cg/kg/min for 72 hours

dosing for eptifbatide

with PCI: 25mcg/kg bolus, then infusion of 0.15mcg/kg/min for 18-24 hours
without PCI: 0.4mcg/kg/min over 30 min; then infusion of 0.1mcg/kg/min for 18-72 hours

dosing for tirofiban

15mg once, then 0.75mg/kg over 30 min, then 0.5mg/kg over 60 min
max total: 100mg

dosing for alteplase

10 units once, then repeat 30 min later

dosing for reteplase

< 60kg: 30mg
60-69kg: 35 mg
70-79kg: 40mg
80-89kg: 45mg
\> 90kg: 50 mg

dosing for tenecteplase