ACS antiplatelet tx, STEMI med tx Flashcards
STEMI : add ASA 81mg daily indefinite tx
what to add for fibrinolytic tx or primary PCI
in hospital
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
2nd antiplatelet agent by the guiidelines
choice and duration of agent determined by
choice of 2nd agent determiend by
indication
in case of STEMI, reperfusion strategy
duration determined by
indication
in case of PCI, stent type
individualized factors when determinging 2nd agent
} Risk of thrombosis } Risk of bleeding } Co-morbidities } Concomitant therapies } Drug interactions } Adverse effects
what does TREAT trial show?
TREAT* trial supports the non-inferiority re major bleeding of switching patients loaded with clopidogrel during fibrinolysis to ticagrelor after 12 hours
see mechanisms slide 55
P2Y12 receptors block ADP mediated platelet aggregation
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
what is PLATO design?
} 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
plato summary
} Ticagrelor ◦ NNT = 53 for death, MI or stroke ◦ NNT = 71 forall cause mortality } No increase in major bleeding ◦ fatal ICH may affect patient selection
medical tx for STEMI
ASA , dual anti Anticoagulation } Beta blockers } ACE inhibitors } Statin } Aldosterone antagonists } Nitroglycerin (long-acting vs rescue)
Anticoagulation
} 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
} Beta blockers
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
Who should continue oral beta blockers
long-term?
◦ 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
ACEi and STEMI
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
ACEi
how long is it continued for?
indicaitons?
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
statin therapy and STEMI
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
mineralocorticoid receptor antagonist (MRA) and STEMI
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
nitroglycerin and STEMI
} 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
◦ Patient counselling
nitroglycerin
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
nitrospray admin instructions
} 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
colchicine
} 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
STEMI drugs at discharge
- DAPT
- ACE inhibitor
- Beta blocker
- Statin
- MRA
- NTG
- Colchicine
Tx at Non ST Elevation MI (NSTEMI)
phases of care (3)
Prehospital •Identification •Transport
Hospital
•Diagnosis
•Risk stratification
•Treatment – including revascularization
Community •Medical management
NSTEMI Revascularization Strategy Dependent Upon Risk
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
what does the GRACE score mean
6 month mortality
higher score = higher mortality
age, HR, SBP, creatinine, cardiac arrest, ST segment deviation, abnormal biomarkers, killip class,
see slide 88 for Major and minor criteria for high bleeding risk according
to the Academic Research Consortium
k
outcome of low-risk pt with ACS
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”
anticoagulation and NSTEMI
} 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
PLATO
tica vs clopd
◦ 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
PCI for STEMI or NSTEACS
intervention Not at high risk of bleeding
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
PCI for STEMI or NSTEACS
intervention at high risk of bleeding
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
