Transcript Pharmacologic management of UA/NSTEMI

Pharmacologic management
of UA/NSTEMI
Nogury, M.S., Pharm.D.
Internal Medicine In-service
UA/NSTEMI
• A clinical syndrome usually caused by
atherosclerotic CAD
• Associated with an increased risk of
cardiac death and MI
• UA vs. NSTEMI
– Ischemia in NSTEMI is severe enough to
have detectable cardiac markers
Pathogenesis of UA/NSTEMI
• Non-occlusive thrombus on pre-existing
plaque
• Dynamic obstruction (coronary spasm or
vasoconstriction)
• Progressive mechanical obstruction
• Inflammation and/or infection
• Secondary UA
Presentation of UA/NSTEMI
• Rest angina: usually > 20 min
• New onset angina: ≥CCS class III
• Increasing angina: more frequent, longer
in duration, or lower in threshold
• Should determine short-term risk of death
or nonfatal MI based on history, character
of pain, clinical findings, ECG changes,
and presence of cardiac markers
Pharmacologic treatment
•
Goals
– Immediate relief of ischemia and the
prevention of serious adverse outcomes
•
Options
1) Anti-ischemic drugs

nitrates, morphine, beta-blockers
2) Anti-platelet drugs & anticoagulants

aspirin, clopidogrel, heparin, LMWH, GPIIb/IIIa
antagonists
3) Risk-modifying drugs

lipid lowering agents (statins)
Nitrates
•
•
•
•
MOA: ↓ preload & afterload → ↓ MVO2
Indicated when chest pain despite SL
NTG x 3
Administered by either IV, topical, or oral
route
IV NTG: initiated with 10 μg/min with
increment of 10 μg/min q3-5min up to
200 μg/min
Nitrates-continued
• Once pt stabilized, may convert to nitropaste
and subsequently po isosorbide
• Does not decrease mortality in AMI
• ADRs: Hypotension, headache, reflex
tachycardia
• Tolerance can develop
• Monitoring parameters: SBP
- ≥110 mmHg in normotensive pts
- ≤ 25% decrease in MAP in hypertensive pts
Morphine sulfate
• Has analgesic, anxiolytic and favorable
hemodynamic effects
• Indicated
– when pain despite SL NTG x 3
– recurrent symptoms despite adequate antiischemic therapy
• 1-5 mg IV q5-30 min
Morphine sulfate-cont’d
• ADRs
– Hypotension, nausea/vomiting, respiratory
depression
• Naloxone (0.4-2.0 mg IV) for morphine
overdose
• Meperidine for morphine allergy pt
Beta-blockers
• Has anti-arrhythmic, anti-ischemic, and
antihypertensive properties
• 13% reduction in MI among pts with UA
• Unless contraindication exists, all pts
should receive intravenous followed by
oral beta-blockers
• CIs: marked 1st degree AV block, 2nd and
3rd degree AV block, severe LV dysfn with
CHF
Beta-blockers cont’d
• Goal: resting HR < 60 bpm
• Do not use β-blockers with ISA
• Should be held when SBP < 90 mmHg or
HR < 50 bpm, decompensated CHF
• ADRs: bradycardia, hypotension,
bronchospasm
• Dosing
– Metoprolol: 5 mg IV q 5 min x 3; followed by
50 mg po q6h for 48 hrs
Beta-blockers cont’d
• Chronic oral therapy
β-blockers
β 1-selective
Elimination
Target dose
Metoprolol
tartarate
(Lopressor)
Yes
Hepatic
100 mg BID
Metoprolol
succinate
(Toprol XL)
Yes
Hepatic
200 mg QD
Atenolol
(Tenormin)
Yes
Renal
50-100 mg
QD
Carvediol
(Coreg)
No
Hepatic
25 mg BID
Calcium antagonists
• ↓ afterload (& ↓ conduction velocity)
• Verapamil or diltiazem is indicated when
beta-blockers are contraindicated
• Dihydropyridine do not have consistent
beneficial effect on mortality or MI
recurrence
• Do not use immediate-release, shortacting nifedipine b/c of ↑ in mortality
Aspirin
• Irreversibly inhibits COX-dependent
platelet activation at low dose (>75 mg/d)
• ↓ mortality and rate of MI, stroke and
vascular death
• All pts should receive aspirin unless
contraindication exists
• At first sign of CP, chew and swallow 325
mg x 1, then continue 81-325 mg qd for
life
Aspirin-cont’d
• Contraindications
– Intolerance, allergy, active bleeding,
hemophilia, active retinal bleeding, severe
untreated hypertension, active peptic ulcer, GI
or GU bleeding
Clopidogrel
•
•
•
•
Irreversible ADP antagonist
Takes several days to show complete
effect
At least as effective as ASA
Dosing
– 300 mg loading followed by 75 mg po QD
Clopidogrel-cont’d
•
Indications
1) when ASA is contraindicated
2) Should be added to ASA ASAP on
admission and given for at least 1 mo and
for up to 9 mo in pts with no early
intervention plan
3) Should be started and continued for at least
1 mo and for up to 9 mo in pts with PCI
planned
 Should be held for at least 5 days,
preferably 7 days, in pts when CABG is
planned
Unfractionated heparin
• Complexes with antithrombin III to inhibit
thrombin, factors Xa, XIa, XIIa and IXa
• Early admin. ↓ the incidence of AMI
• Should be added to ASA + clopidogrel
• Dosing
– 60~70 U/kg bolus (max: 5,000 U) followed by 12~15
U/kg/h (max: 1,000 U/kg/h)
• Duration: undefined for asymptomatic pts or
continued until an invasive intervention in
symptomatic pts
Unfractionated heparin-cont’d
• Monitoring parameters
– aPTT at 1.5-2.5 times control values
– aPTT q6h after initiating therapy and after
subsequent dosage adjustment
– Once 2 consecutive aPPTs within the target,
aPTT q24h
– PLT, Hct/Hgb
• ADRs
– Thrombocytopenia: not-dose and not-duration
dependent
Low Molecular Weight Heparin
•
•
More selective for factor Xa compared to
thrombin
Advantages:
– More predictable and sustained
anticoagulation b/c of dose-independent
clearance with longer t1/2
– Do not usually require lab monitoring activity
•
Enoxaparin may be superior to UFH in
the treatment of UA
Low Molecular Weight Heparin
-cont’d
•
•
Enoxaparin dosing: 1 mg/kg SC q12h
Should Not be used
1) CrCl <30 ml/min
2) Very obese: >120 kg
•
May monitor antifactor Xa 4hr after the
admin.
 UFH is preferred in pts likely to undergo
CABG within 24h, b/c of the reversibility
of anticoagulating effect
 LMWH should be held at least 8 hr
before the intervention
GPIIb/IIIa antagonists
•
•
•
Inhibits platelet aggregation by blocking
GPIIb/IIIa receptor to which fibrinogen
binds
Abciximab, eptifibatide, tirofiban
Indications
1) Should be given, in addition to ASA,
clopidogrel and UFH, to pts when
catheterization and PCI are planned
2) Should be given, in addition to ASA and
UFH or LMWH, to pts with continuing
ischemia or an elevated troponin
GPIIb/IIIa antagonists
Abciximab
(Reopro)
Eptifibatide
(Integrelin)
Tirofiban
(Aggrastat)
Renal
Dosing
Elimination
T1/2
ADRs
IIb/IIIa
selectivity
Proteolytic
breakdown
Short
but high
affinity
Bleeding
Thrombocytopenia
No
No
Renal
2.5 h
Bleeding
Thrombocytopenia
Yes
Yes
Renal
1.5-3
hr
Bleeding
Thrombocytopenia
Yes
Yes
Monitor plt 2-4 hr after bolus and then daily (Reopro), 6 hr after
bolus and then daily (Integrelin & Aggrastat)
ACE I
•
•
↓ LV dysfn and slow progression to HF
by preventing LV remodelling
↓ mortality in pts
1)
2)
3)
4)
•
with AMI
who recently had an MI, and have LV dysfn
in diabetic pts with LV dysfn
in a broad spectrum of pts with high-risk chronic
CAD, including pts with normal LV fn
Initiated after ASA + clopidogrel and betablockers when pt is hemodynamically
stable
ACE I-cont’d
•
Contraindications
–
–
–
–
–
–
•
Hypotension
Bilateral renal artery stenosis
Acute renal failure
Angioedema
Pregnancy
Hyperkalemia
ADRs
– Hyperkalemia, angioedema, dry cough,
hypotension
ACE I-cont’d
Initial dose
(mg, po)
Target dose
(mg, po)
Captopril
6.25-12.5, TID
50, TID
Enalapril
2.5-5, QD
10, BID
Lisinopril
2.5-5, QD
20, QD
Ramipril
1.25-2.5, QD
5, BID
Trandolapril
1, QD
4, QD
Lipid lowering agents (Statins)
•
•
•
Inhibits HMG-CoA reductase, a rate limiting
enzyme of cholesterol biosynthesis
↓ rate of AMI
Goal
1)
2)
•
•
LDL < 100 mg/dL
HDL > 40 mg/dL
Should be initiated 24-96 hr after admission
May provide benefit independent of lipid
lowering effect
Other modifiable risks
• Hypertension
• Smoking
• Diabetes
Typical discharge regimen
•
•
•
•
•
SL NTG
Clopidogrel + ASA
Beta-blocker
ACE I
Statin
References
1.
Braunwald et al, ACC/AHA guideline update for the
management of patients with unstable angina and non-STsegment elevation myocardial infarction. 2002
www.acc.org/clinical/guidlines/unstable/unstable.pdf
Abbreviations
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
UA: unstable angina
NSTEMI: non ST segment elevation myocardial infarction
CAD: coronary artery diseases
MI: myocardial infarction
CCS: Canadian Cardiovascular Society
ECG: electrocardiogram
LMWH: low molecular weight heparin
GPIIb/IIIa: glycoprotein IIb/IIIa
MOA: mechanism of action
MVO2: myocardial wall tension
SL NTG: subligual nitroglycerin
AMI: acute myocardial infarction
ADRs: adverse drug reactions
SBP: systolic blood pressure
MAP: mean arterial blood pressure
Abbreviations
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Pt(s): patient(s)
CIs: contraindications
AV: atrioventricular
LV: left ventricular
Dysfn: dysfunction
CHF: congestive heart failure
HR: heart rate
ISA: intrinsic sympathomimetic activity
bpm: beat per minute
b/c: because
COX: cyclooxygenase
CP: chest pain
GI: gastrointestinal
GU: genitourinary
ADP: adenosine diphosphate
ASA: aspirin
ASAP: as soon as possible
Abbreviations
•
•
•
•
•
•
•
•
•
•
•
•
PCI: percutaneous coronary intervention
CABG: coronary artery bypass graft
aPTT: activated partial thrombin time
PLT: platelet
Hct: hematocrit
Hgb: hemoglobin
UFH: unfractionated heparin
CrCl: creatinine clearance
HF: heart failure
HMG: hydroxymethylglutaryl
LDL: low density lipoprotein
HDL: high density lipoprotein