Mx of UA and NSTEMI
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Transcript of Mx of UA and NSTEMI
Mx of UA and NSTEMIAlyssa Morris, R4September 30, 2010
OBJECTIVES
Mx of UA/NSTEMI in the ED CRUSADE, COMMIT, ISIS-2, CAPRIE, CURE,
PCI-CURE, OASIS-5, OASIS- 7, SYNERGYNOT covering
GPIIb/IIIa inhibitors Statins Decision to go to PCI or medical
management Variants of ACS
LEVEL OF EVIDENCE
See handout
TERMINOLOGY
Stable Angina Angina brought on by exertion and
relieved with predictable measures (rest/NTG)
Unstable Angina/ACS New onset angina w/i 2/12 and at least
CCS III Rest angina lasting >20min w/i 1wk of
angina Change from baseline
NSTEMI/ACS + markers
TERMINOLOGY Acute Coronary Syndromes is the
preferred terminology to refer a spectrum of disease related to myocardial ischemia
(stable angina)
Unstable Angina
NSTEMI
STEMI
+/- abN ECG, -ve markers
+/- abN ECG, +ve markers
STE on ECG, +ve markers
CASE
60M with RSCP with a +TNT at 6 hrs after pain started, no STE on multiple ECGs
BP= 176/98, P= 90, 02= 94%How would you treat this
person? Write down all that you would do What do you think the NNT for each of
your therapies is?
TREATMENT STRATEGIES
ANTI-ISCHEMIC Inc supply: nitrates, oxygen Dec demand: BB, morphine, ACE-I
ANTI-PLATELET ASA, Clopidogrel, GPIIb/IIIa inhibitors
ANTI-THROMBOTIC Medical: UFH, LMWH, thrombolytics Invasive: PCI/CABG
ANTI-INFLAMMATORY Statins
ANTI-ISCHEMIC TREATMENT
OXYGEN- AHA guidelines
LOE: B Administered to UA/NSTEMI pts with:
Sa02<90% Respiratory distress Other high-risk features for hypoxemia
LOE: C Reasonable to administer to all
patients in 1st 6hrs from presentation
NITRATES
Reduces myocardial oxygen demand while enhancing myocardial oxygen delivery
Venous dilation Arterial dilation
Peripheral and coronary arteries
NITRATES- AHA guidelines LOE: C Sublingual NTG for ongoing ischemic
discomfort 0.4mg Q5min, max of 3 doses
Assess need for IV NTG Persistent pain, HF, HTN Q: How do you titrate your nitro drip?
Not if SBP<90, HR<50, PDE I in last 24-48hr
MORPHINE- AHA guidelines Venodilation Modest reductions in HR (inc vagal
tone)Modest reductions in SBP
CLASS IIa/ LOE B Reasonable to administer it IV if
uncontrolled ischemic chest pain despite NTG
Provided you use additional therapy to manage the ischemia
Nonrandomized, retrospective, observational study
N= 57,039 (w NSTEMI) 17,003 (29.8%) received morphine
Higher adjusted risk of death (OR 1.48, 95% CI 1.33-1.64
BETA BLOCKERS
Competitively block the effects of catecholamines on cell membrane R Reduce myocardial contractility Reduce sinus node rate Reduces AV node conduction
velocity
Randomized trial N= 45,852
93% had STE or LBBB 7% had NSTEMI
Randomized to metoprolol or placebo IV max 15mg then 200mg PO OD
No reduction in composite of death, reinfarction or cardiac arrest Less VFIB later in study
Increased risk of cardiogenic shock in 1st day
BETA BLOCKERS- AHA guidelinesCLASS I/ LOE B
Oral BB should be started w/i 24hr in patients who do not have 1 of:1) Signs of HF, 2) low-output state, 3)
increased risk for cardiogenic shock, 4) other contraindications to BB
CLASS II/ LOE B Reasonable to administer IV BB at time
of presentation for HTN who do not have 1 of above
CCBs
Reduce cell transmembrane inward Ca flux Inhibits myocardial and vascular smooth
muscle contraction Some also slow AV conduction and
depress sinus node impulse formation Verapamil and diltiazem
Coronary dilation Benefit is from reduced myocardial
oxygen demand and improved myocardial flow
CCBs- AHA guidelines
CLASS I/ LOE B Nondihydropyridine CCBs should be given
to pts with ongoing or frequently occurring ischemic pain in whom BB are contraindicated
Not if LV dysfunction or other CIsCLASS IIb/ LOE B
Can use ER nondihydropyridine CCB instead of a BB
Can only use IR dihydropyridine in adequately BB pt
ACE-I – AHA guidelines
CLASS I/ LOE A Should be started orally w/i 24h in pts
with pulmonary congestion or LVEF <0.4 in absence of hypotension (SBP<100)
CLASS IIa/ LOE B Can be used in patients w/o pulmonary
congestion or LVEF <0.4CLASS III
IV should not be given in the 1st 24h b/c of increased risk of hypotension
NSAIDS- AHA guidelines
CLASS I/LOE C b/c of increased risk of mortality,
reinfarction, htn, HF and myocardial rupture associated with their use, NSAIDs (except ASA) should be discontinued and not administered
ANTIPLATELET TREATMENT
ASA
Irreversibly inhibits COX-1 w/i platelets Diminishes platelet aggregation Fully present even with low dose
ASA
Meta-analyses of RCTs 195 trials, 143,000 patients22% reduction in the odds of
vascular death, MI, or strokeARR 6.1%, NNT 1675mg to 1500mg of ASA showed
similar reductions in the odds of vascular events
RCT N= 17,187 pts with suspected acute
MI Randomized to 1month of ASA
26 fewer deaths per 1000 during first 35d
ARR for 35d mortality 2.4% RRR for 35d mortality 23% NNT=43 (to prevent one death) Showed benefit if given early
ASA- AHA guidelines
CLASS I/ LOE A ASA should be administered asap and
continued indefinitely In pts with hx of GIB a PPI should be
used CIs
Intolerance and allergy Active bleeding Hemophilia Severe untreated htn
PLAVIX
Platelet effects are irreversible but take several days to achieve Loading dose shortens this time
substantiallyDifferent mechanism than ASA
Potential exists for for additive benefit
Adenosine diphosphate receptor antagonist
Randomised, blinded international study
Efficacy of ASA and Clopidogrel (75mg OD) in reducing risk of a composite of ischemic stroke, MI, vascular death
N= 19,185, Included recent ischemic stroke, MI or symptomatic peripheral artery dz
Plavix annual risk of 5.32% vs ASA 5.83% (P=0.043) (NNT= 194)
No difference in AE
RCT N= 12,562 with UA/NSTEMI Placebo or Clopidogrel (300mg loading
dose then 75mg daily) All pts received ASA Outcome: 1) composite of death from CV
cause, MI or stroke 2) refractory ischemia Results: 1) placebo 11.4% vs Clopidogrel
9.3% 2) placebo 18.8% vs clopidogrel 16.5% (p<0.001) (20% RRR, 2.1% ARR, NNT= 48)
Observational substudy of CURE N= 2658 pts undergoing PCI Received the loading dose of Plavix
then daily for 10 days, then they got thienopyridine for 4 weeks, then plavix restarted
Outcome: composite of death, MI or urgent revascularization
Results: placebo 6.4% vs clopidogrel 4.5% (p=0.03) (ARR= 3.8%, NNT= 26)
RCT 45852 pts, 7% had UA/NSTEMI Plavix 75mg OD or placebo Outcomes: 1) composite of death,
reinfarction or stroke; 2) death from any cause
ARR 0.9% and NNT 111 Concluded that adding plavix to ASA
safely reduces mortality and major vascular evens and should be done routinely
Plavix- How much?
Approved loading dose in UA/NSTEMI is 300mg
600mg does achieve antiplatelet fxn more quickly Not enough good evidence to use this much
Considerable inter-individual variation in antiplatelet effect with all loading doses
O mg if you believe pt going to CABG Increased risk of minor bleeding Some believe benefit outweighs risk
RCT2x2 factorial design N= 25,086 w ACS, >70% had UA/NSTEMI Invasive strategy + loading dose of 600mg
Plavix or 300mg Plavix High or low dose ASA also given randomly Outcome: cardiovascular death, myocardial
infarction or stroke at 30d 4.2% in high Plavix vs 4.4% standard Plavix Secondary outcome of stent thrombosis in
those with PCI (HD 1.6% v SD 2.3%, p= 0.001)
PLAVIX – AHA guidelines
CLASS I Plavix should be given to pts who are
unable to take ASA (LOE A) Pts with hx GIB should get a PPI if getting
Plavix (LOE B) Plavix should be given to pts in addition
to ASA in pts who are receiving an initial invasive stratgey (LOE B)
Plavix should be given to pts in addition to ASA in pts who are receiving conservative therapy (LOE B)
ANTICOAGULANT TREATMENT
UFH
UFH Accelerates action of antithrombin
inactivates factor IIa (thrombin), factor IXa and Xa
Prevents thrombus propagation but does not lyse existing thrombi
Binds to a number of plasma proteins, blood cells and endothelial cells
LMWH
LMWH From depolymerization of chains of
heparin Inactivate Xa>IIa (b/c of molecular weight) Advantages:▪ decreased binding to plasma proteins and
endothelial cells ▪ Dose-independent clearance ▪ Longer half-life that results in more
predictable and sustained anticoagulation w SC administration
Synthetic Factor Xa Inhibitors Fondaparinux
Synthetic pentasaccharide Acts proximally in cascade to inhibit
multiplier effects of the downstream coagulation rxns reduce amount of thrombi that is generated
Indirect, selective factor Xa inhibitor Binds to antithrombin III Same advantages as LMWH
Fondaparinux: pharmacology
Pharmacologic comparisonPharmacotherapy 23(6):772-787, 2003Property UFH LMWH FondaparinuxSource animal animal synthetic
T1/2 ~3h ~4h (variable) 17-21hBioavailability
(SC) 30% >90% 100%
Elimination Reticuloendothelial and renal renal renal
Induced HIT* 2-5% 1-2% Not observedInter or intra-
patient variability
+++ ++ +
Monitoring aPTTPlt count Plt count nil
Reversal Protamine Protamine FFP
Prospective, randomized, open-label N= 10027 high-risk UA/NSTEMI pts w early
invasive strategy Compare enoxaparin to UFH for composite
endpoint of all-cause death or MI in 30d 14% in enox group vs 14.5% in UFH group
(p=0.4) More bleeding in enox group
Post-hoc showed from switching type of anticoagulant at time of PCI
Low molecular weight heparins vs unfrctionated heparin for acute coronary syndromesMagee KD, Sevcik W, Moher D, Rowe BH
To assess the effects of LMWH compared to UFH for ACS (UA/NSTEMI)
7 studies involving over 10,000 people No difference in overall mortality LMWH showed reduced recurrence of MI
and the need for revascularization procedures
No difference in recurrent angina, major bleeds, or minor bleeds; there was a decrease in the incidence of HIT
125 patients have to be treated with LMWH to prevent 1 MI, and 50 have to be treated to prevent 1 revascularization procedure
Cochrane Database of Systematic Reviews 2003
N=
RCDBT, industry sponsored, non-inferiority
N= 20,078, UA/NSTEMI patients Enox 1mg SC BID v Fonda 2.5mg SC
OD + UFH at PCI if last dose >6hr ago
Outcomes: 1) death, MI or refractory ischemia at 9d; 2) major bleeding
1) 5.8% w fonda v 5.7% w enox Satisfies non-inferiority criteria
2) 2.2% w fonda v 4.1% w enox (p<0.001)
ANTICOAGULANT Mx- AHA guidelines CLASS I
Should be added to antiplt therapy at presentation Invasive Strategy LOE A▪ UFH or Enoxaparin
Invasive Strategy LOE B ▪ Fondaparinux
Conservative strategy LOE A▪ UFH or enoxaparin
Conservative strategy LOE B▪ Fondaparinux
Use fondaparinux if increased risk of bleeding
SUMMARY
BB ASA
NNT 16 in meta-analysis NNT 43 in ISIS-2
Plavix NNT 48 in CURE NNT 194 in CAPRIE NNT 26 in PCI-CURE NNT 111 in COMMIT
Anticoagulant