ACS NSTEMI med tx Flashcards
med therapy of NSTEMI
ASA anticoag } Beta blockers } ACE inhibitors } Statin therapy } Nitroglycerin (long-acting vs rescue)
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 NSTEMI
} Continued indefinitely for cardiovascular protection, if no contraindications
◦ Dosing from different trials 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 NSTEMI
} Acute management of unstable atheroma
} Early and intensive statin therapy (in comparison to
placebo) significantly decreased combined endpoint of death, MI, cardiac arrest and recurrent ischemia
} 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
nitroglycerin and NSTEMI
} Long-Acting
◦ No benefit on clinical outcomes
◦ Useful for recurrent angina if treatment 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
recommendations for MRAs and PPIs
MRAs are recommended in patients with heart failure with reduced LVEF (<40%) in order to reduce all-cause and cardiovascular mortality and cardiovascular morbidity.
Proton pump inhibitors
Concomitant use of a proton pump inhibitor is recommended in patients receiving aspirin monotherapy, DAPT, DAT, TAT, or OAC monotherapy who are at high risk of gastrointestinal bleeding in order to reduce the risk of gastric bleeds
secondary prevention recommendations for ACS
} Referral to a comprehensive outpatient
cardiovascular rehabilitation program
} Reasonable to screen for depression
} Annual influenza vaccination and pneumococcal vaccination initially and at 5 years
tobacco use
pharmacist role
} At every visit: ◦ Ask about tobacco use ◦ Advise users to quit ◦ Assess willingness to quit ◦ Assist by counselling and development of plan for quitting – including pharmacotherapy and/or referral as required ◦ Arrange follow-up
bleed risk with low dose ASA
} ASA vs placebo
◦ Risk of any major bleed 1.71 (1.41-2.08)
◦ Risk of major GIB 2.07 (1.61-2.66)
NNH=833 at one year
Doub;les risk of bleed from placebo
} 5 year observational cohort from Denmark
◦ RR of hospitalization for upper GIB with low-dose
ASA alone 2.6 (2.2-2.9)
◦ No difference with enteric coated and uncoated ASA
Baseline bleed risk is quite low so baby ASA a day is ok
Dual antiplatelet further increases the risk
Intracranial bleeding
bleed risk with dual antiplatelet
tic + ASA more bleeding than ASA alone
dual tx with tic + ASA does not sig increase major b leeding compared to clop + ASA
ASA vs ASA/clopidogrel (CURE)
◦ Risk of any major bleed RRR 0.27 (0.12-0.40)
◦ Risk of major GIB RRR 0.44 (0.20-0.61)
◦ Risk of intracranial bleed NS
} Clopidogrel vs ASA/clopidogrel (MATCH)
◦ Risk of any major bleed RRR 0.58 (0.45-0.68)
◦ Risk of major GIB RRR 0.66 (0.49-0.77)
◦ Risk of intracranial bleed NS
further increases bleeding
TIMI majopr bleeds
one type of scoring system
cohorts
◦ Any intracranial bleeding
◦ Bleeding that results in death
◦ Clinically overt signs of hemorrhage associated with
a drop in Hgb of >50
} Rates of 2-3% with dual antiplatelet therapy
nuisance bleeding with dual antiplatelet tx
} Single center observational study of 2360
patients with DES implantation
} Bleeding events included superficial – easy
bruising, bleeding from small cuts, petechia,
ecchymosis, as well as internal and alarming
} Telephone follow-up or office visit
} Bleeding events self-reported
diff tyoes of bleeding events (3)
} 32.5% of patients reported bleeding events
} Most bleeding events were classified as
} Nuisance – 85.7%
} Internal – 13.6%
} Alarming – 0.7%
rates of d/c tx high in intrnal bleeding vs nuisance, highest dropout in clopidogrel
least with both therapy
chronic DAPT therapy
considerations
} Careful patient hx, physical examination
and assignment to therapy
◦ Individual patient’s risk factors
◦ Impact of non-cardiac concomitant therapies
} Appropriate duration of antithrombotic
regimens
} Consider use of proton pump inhibitors for
mitigating GI bleed risk
} Consider more frequent monitoring and
closer follow-up in high risk patients
Factors associated with increased
bleeding risk
} Patients need to be aware of the signs of
serious bleeding and understand when they
need to seek medical attention
} Patients need to know to contact a health
care professional to ensure appropriate
management if they experience side effects
that may be due to antiplatelet therapy,
rather than just stopping the medication
- Need for OAC in addition to DAPT
- Advanced age (> 75 years)
- Frailty
- Anemia with hemoglobin < 110 g/dL
- Chronic renal failure (creatinine clearance < 40 mL/min)
- Low Body Weight (< 60 kg)
- Hospitalization for bleeding within last year
- Prior stroke/intracranical bleed
- Regular need for NSAIDS or prednisone
what are otehr AE of ticagrelor
◦ Mild and usually self-limiting dyspnea
◦ 1/3 of patients will have resolution within a week
◦ Considered reversible upon discontinuation
◦ Need for investigation of new, prolonged or
worsening dyspnea
◦ Limited data in patients with asthma and COPD
dysnea higher with tica than clopid
what are otehr AE of clopid
~4% of patients ◦ Pruritic macular erythematous confluent rash on trunk ◦ Usually presents on day 6 of therapy } Ticagrelor as alternative
clopid responsiveness 2 factors (20
} Genetic
◦ Polymorphism
} Pharmacokinetic
◦ Prodrug
◦ Reduced generation of active metabolites due to
variability in intestinal absorption and CYP450 2C19
availability / activity
interaction b/w clopid and PPI
We recommend selective use of PPIs in patients
receiving DAPT at high risk of upper
gastrointestinal bleeding
We suggest that prescribing a PPI that minimally inhibits CYP2C19 (e.g. pantoprazole) be considered in patients receiving a PPI with clopidogrel
ticagrelor admined with CYP34a inhibitors
} Concurrent administration with ketoconazole
increased the Cmax of ticagrelor 2.4-fold and
AUC 7.3-fold
} Cmax of the active metabolite reduced 89%
and AUC of active metabolite reduced 56%
} Co-administration of any strong 3A4
inhibitor is contraindicated
ticagrelor admined with CYP34a inducers
} Concurrent administration with rifampin decreased the Cmax of ticagrelor 73% and AUC 86%
} AUC of active metabolite reduced 46%
} Platelet aggregation inhibition reduced by 27%
} Co-administration of any strong 3A4 inducer
is contraindicated
pharmacodynamic of tic
Increased risk of bleeding when combined
with other agents that also increase this risk
} Addition of oral anticoagulants (including
DOACs) likely increase bleed risk two-fold
} Caution re multiple prescribers and intent
predictors of discontinution
Older
} Less likely to have completed high school
} Less likely to be married
} More likely to avoid health care due to cost
} Pre-existing cardiovascular disease
} Anemia at presentation
} Less likely to have been given discharge
instructions re medications
} Less likely to have been referred to cardiac
rehab
discontinuation and one-year mortality
} All cause mortality 7.5% for patients who discontinued clopidogrel within 30 days compared to 0.7% for those who continued therapy (P<0.0001) } After adjustment, HR 9.02 (1.3-60.6)
Non-adherence to medication is associated with increased mortality
} Education level (possibly health literacy) appears to be a risk factor for discontinuation of therapy
} Health policy can also impact patient compliance
what pharmacists can do to improve adherence
Patient education } Pharmacists should address cost issues } DAPT should be included in automated follow-up systems } If antiplatelet agents are discontinued for a procedure, patients should receive clear written and verbal directions on when to resume therapy
key educational messages for dual antiplatelet therapy
} ASA is lifelong therapy
} Patients should know the duration of their
DAPT and the potential consequences of early
discontinuation or non-adherence
} Patients should know to inform other HCP that they are taking antiplatelet agents and that they should not stop their ASA or antiplatelet agents without speaking with their cardiologist
} pt need to be aware of the signs of serious bleeding and understand when they need to seek medical attention
} pt need to know to contact a HCP to ensure appropriate management if they experience side effects that may be due to antiplatelet therapy, rather than just stopping the medication
