ACS antiplatelet tx, STEMI med tx

Question 1

STEMI : add ASA 81mg daily indefinite tx

what to add for fibrinolytic tx or primary PCI
in hospital

Answer 1

fibrolytic tx or no reperfusion tx: add clopidogrel for at least 1 month and up to 12 months

primary PCI: add prasugrel or ticagrelor for 12 months

if pt ineligible for prasugrel or tic, add clopid for 12 months

Question 2

2nd antiplatelet agent by the guiidelines

choice and duration of agent determined by

Answer 2

choice of 2nd agent determiend by

indication
in case of STEMI, reperfusion strategy

duration determined by

indication
in case of PCI, stent type

Question 3

individualized factors when determinging 2nd agent

Answer 3

} Risk of thrombosis
} Risk of bleeding
} Co-morbidities
} Concomitant therapies
} Drug interactions
} Adverse effects

Question 4

what does TREAT trial show?

Answer 4

TREAT* trial supports the
non-inferiority re major bleeding of
switching patients loaded with
clopidogrel during fibrinolysis to
ticagrelor after 12 hours

Question 5

see mechanisms slide 55

P2Y12 receptors block ADP mediated platelet aggregation

Answer 5

ok

Clopidogrel (grey) occupies the receptor and prevents activation

Ticagrelor occupies a diff part of the receptor and alters conformation so ADP can’t bind and binds to a diff spot

clopid binds irreversibly, ticagrelow binds reversibly

clopid is a prodrug and needs 2-step activation
- CYP2C19 and oxidation to get active compound and there is potential for drug interactions during the activation steps

tic is orally active but also has an active metabolite (30-40% of activity) by CYP3A4
- both parent compound and active metabolite is further broken by CYP3A4 into inactive pdts

Question 6

what is PLATO design?

Answer 6

} Design: Randomized, double-blind trial
} Intervention: Clopidogrel 75mg daily vs
Ticagrelor 90mg BID – with ASA 75-100mg
daily for total of 12 months
} Patients: 18,624 ACS patients within 24 h of
symptom onset
◦ Without ST elevation or STEMI with intent for
primary PCI – not fibrinolysis
} Outcomes: Time to first occurrence of
composite of death from vascular causes, MI
or stroke

Question 7

plato summary

Answer 7

} Ticagrelor
◦ NNT = 53 for death, MI or stroke
◦ NNT = 71 forall cause mortality
} No increase in major bleeding
◦ fatal ICH may affect patient selection

Question 8

medical tx for STEMI

Answer 8

ASA , dual anti
Anticoagulation
} Beta blockers
} ACE inhibitors
} Statin
} Aldosterone antagonists
} Nitroglycerin (long-acting vs rescue)

Question 9

Anticoagulation

Answer 9

} In-hospital duration of parenteral anticoagulants related to reperfusion strategy but stopped prior to discharge
} Chronic oral anticoagulants only for the
infrequent occurrence of ventricular clot with large anterior STEMI
} Other diagnoses, cardiac and non-cardiac,
may require chronic anticoagulation

Question 10

} Beta blockers

Answer 10

Anti-ischemic
} Reduction of tachyarrhythmias
} Prevention of adverse remodelling

} Oral beta blockade to be started within the
first 24 hours unless:
◦ Heart failure
◦ Risk for shock or evidence of low output state
◦ Contraindications – i.e. heart block
◦ In these cases, beta blocker initiation may need to
be delayed to when the patient is more stable

Question 11

Who should continue oral beta blockers

long-term?

Answer 11

◦ All patients with heart failure or left ventricular
systolic dysfunction (LVSD)
◦ All others, except those at low risk (by score or
assessment at follow-up) or with contraindications
} Target doses if tolerated:
◦ metoprolol 100mg BID
◦ carvedilol 25mg BID
◦ bisoprolol 10mg daily

Question 12

ACEi and STEMI

Answer 12

Mortality benefit of short-term therapy (4 to
6 weeks), started acutely
◦ Likely most benefit for anterior infarcts, EF<40% or
heart failure
◦ ARBs for those intolerant of ACEi

Drug Initial Dose, Target Dose
Lisinopril 2.5 to 5mg daily
10mg or higher

Ramipril 2.5mg BID
5mg BID

Trandolapril 0.5mg daily
4mg daily

Valsartan 20mg BID
160mg BID

Question 13

ACEi
how long is it continued for?
indicaitons?

Answer 13

Continued indefinitely for cardiovascular
protection, if no contraindications
◦ Different trials with different dosing in stable CAD
} Heart failure or left ventricular systolic
dysfunction (LVSD)
} Hypertension, diabetes or stable chronic
kidney disease
} ARBs for those intolerant of ACEi
} Hypotension, hyperkalemia and renal
dysfunction

Question 14

statin therapy and STEMI

Answer 14

Acute management of unstable atheroma
} In NSTEMI, early and intensive statin therapy (in comparison to placebo) significantly decreased combined endpoint of death, MI, cardiac arrest and recurrent ischemia
} Trial evidence extrapolated to STEMI
} Initiate high intensity statin therapy
◦ Atorvastatin 80mg po daily
◦ Rosuvastatin 40mg po daily

For ACS, more intensive statin therapy long-term decreased clinical events
} Intensive vs less intensive comparisons rather than specific LDL level achieved

Question 15

mineralocorticoid receptor antagonist (MRA) and STEMI

Answer 15

An aldosterone antagonist should be given to
patients with STEMI (and no contraindications) who are already receiving an ACEi and a beta blocker and who have an EF <40% AND either symptomatic heart failure or diabetes
} Spironolactone versus eplerenone
} Caution re renal dysfunction and hyperkalemia DB, PC, RCT with eplerenone 25mg (titrated to 50mg) starting 3 to 14 days after AMI in patients with EF <40% and heart failure (diabetics did not have to have symptoms of heart failure) receiving optimal medical
therapy
} Decreased mortality and hospitalizations for CV reasons
} Increased risk of hyperkalemia

Question 16

nitroglycerin and STEMI

Answer 16

} Long-Acting
◦ No benefit on clinical outcomes
◦ Useful for recurrent angina if usage does not preclude beta blockers
◦ Importance of nitrate free interval
} Useful chronically for symptomatic management of stable angina
} Sublingual for rescue
◦ All patients should have available
Importance of priming, expiry date and supply in bottle

◦ Drug interactions with PDE inhibitors

Question 17

◦ Patient counselling

nitroglycerin

Answer 17

0.4mg SL spray or 0.3mg SL tablets every 5 minutes up to 3 doses
Caution re lightheadedness and dizziness
Directions to call 911 after first dose is no improvement or worsening of symptoms

} Increase supply of blood and oxygen to the heart while decreasing workload which can ease chest pain
} No need to ‘save’ it for very bad pain
◦ Expectation of headache and not a reason to avoid use
} Keep track of how often you need to use it and what you were doing and share this information with your doctor or pharmacist

Question 18

nitrospray admin instructions

Answer 18

} Remove plastic cap
} Do not shake
} Prime if required
} Hold upright. Open mouth and bring container as close as possible.
} Press button firmly to release spray onto or under tongue
} Do not inhale or breathe in spray
} Close mouth. Do not spit out or rinse mouth.
} Replace plastic cap

Question 19

colchicine

Answer 19

} DB, PC, RCT of colchicine 0.5mg daily starting within 30 days after AMI in 4745 patients receiving optimal medical therapy
} Decreased CV death, resuscitated arrest, MI, stroke or urgent hospitalization with revascularization over nearly 2 years
} NNT = 63
} GI events common in both groups with nausea and flatulence occurring significantly more often with colchicine
} Drug interactions

Question 20

STEMI drugs at discharge

Answer 20

• DAPT
• ACE inhibitor
• Beta blocker
• Statin
• MRA
• NTG
• Colchicine

Question 21

Tx at Non ST Elevation MI (NSTEMI)

phases of care (3)

Answer 21

Prehospital •Identification •Transport

Hospital
•Diagnosis
•Risk stratification
•Treatment – including revascularization

Community •Medical management

Question 22

NSTEMI Revascularization Strategy Dependent Upon Risk

Answer 22

Recurrent Ischemic Event

} Determined by an interaction between
patient’s pre-event status and impact of
the acute event

Bleeding
} Increased by intensive antithrombotic
therapy and invasive management

Viagra can’t use within 24 hoyurs
Cialis 48-72 hours

Patches too

Question 23

what does the GRACE score mean

Answer 23

6 month mortality
higher score = higher mortality
age, HR, SBP, creatinine, cardiac arrest, ST segment deviation, abnormal biomarkers, killip class,

Question 24

see slide 88 for Major and minor criteria for high bleeding risk according
to the Academic Research Consortium

Answer 24

k

Question 25

outcome of low-risk pt with ACS

Answer 25

Presentation with UA in the absence of dynamic ECG changes, no troponin elevation, no arrhythmia nor hypotension
} Abnormal ECG in 38%,
} 27% stress test, 37% echo, 52% angio
} 6 month outcome:
◦ 23% readmission
◦ 12% revascularized
◦ 3% deaths
} “Low-risk” is not “No risk”

Question 26

anticoagulation and NSTEMI

Answer 26

} Parenteral anticoagulation, in addition to antiplatelet therapy, at diagnosis and during revascularization procedures
} In-hospital duration related to revascularization in some cases but stopped prior to discharge
} Other diagnoses, cardiac and non-cardiac, may require chronic anticoagulation

ASA 81mg daily
for PCI, CABG surgery, medical therapy add ticagrelor for 12 months
clopdiogrel if cant use tic

Combination decreased CV death and stroke

Increased bleeding with dual antiplatelet therapy compared to ASA alone

Question 27

PLATO

tica vs clopd

Answer 27

◦ Without ST elevation or STEMI with intent for primary PCI – not fibrinolysis
tica vs clopid
Primary 9.8 11.7 
Mortality 4.5 5.9
Stent thrombosis 1.3 1.9
TIMI major 7.9 7.7

Ticag does not increase bleeding compared to clopid + ASA

Question 28

PCI for STEMI or NSTEACS

intervention Not at high risk of bleeding

Answer 28

DAPT for 1 year
ASA 81 mg OD +
Ticagrelor 90 mg BID or Prasugrel 10 mg OD
preferred over
Clopidogrel 75 mg OD

At 1 year, determine bleeding risk

Not at high risk of bleeding

Continue DAPT for up to 3 years
ASA 81 mg OD +
Ticagrelor 60 mg BID or
Clopidogrel 75 mg OD2

Question 29

PCI for STEMI or NSTEACS

intervention at high risk of bleeding

Answer 29

DAPT for 1 year
ASA 81 mg OD +
Ticagrelor 90 mg BID or Prasugrel 10 mg OD
preferred over
Clopidogrel 75 mg OD

At 1 year, determine bleeding risk

High risk of bleeding

SAPT
ASA 81 mg OD
or
Clopidogrel 75 mg OD