Transcript INTEGRILIN® (eptifibatide) - University of Wisconsin School of

CARE OF NSTEMI PATIENTS
LATEST GUIDELINES
Rick Barney MD FACEP
Emergency Medicine Beloit Memorial and
University of Wisconsin
New NSTEMI Guidelines by ACC/AHA
Released August 6th 2007
www.americanheart.org
NSTEMI Protocols not followed well
 STEMI- straight forward and well followed
 NSTEMI- no hospital agreement, under use of available
treatment, no agreement even amongst cardiologists
Following ACC/AHA Guidelines
Significantly Reduces Risk of Mortality
Incidence of in-hospital mortality was lower with adherence to ACC/AHA Guidelines
Nonadherence
to ACC/AHA
Guidelines
3.7%
(n = 9,889)
32.4%↓
(P < 0.001)
Adherence to
ACC/AHA
Guidelines
Bhatt DL, et al. JAMA. 2004;292(17):2096-2104.
2.5%
(n = 8,037)
NSTEMI- Definition
Coronary symptoms with ST segment
depression, or T wave inversions (new)
and/or elevated biomarkers (Troponin
preferred)
Nitro Recommendation
 If new angina pattern, call 911 if one single nitro has not
helped. Take 2nd and 3rd dose while waiting for EMS
arrival
 If typical stable angina pattern, still recommend call for
help if three nitro doses 5 minutes apart does not help.
Aspirin and Pre-Hospital 12 lead ECG
 Aspirin should be given immediately to all patients who
may have a coronary Syndrome. Only reason to not give
is a true allergy.
 Strong recommendation for pre-hospital 12 lead analysis
Positive Biomarkers are critical to ED
Care
Latest studies show patients with positive
Troponins do best with early invasive
management, Clopidogrel, anticoagulation,
and glycoprotien II b III a inhibition.
USE OF BETA BLOCKERS
COMMIT Trial shows some risk in using IV
Metoprolol.
For NSTEMI-use IV if hyperdynamic,
otherwise PO within 24 hours of arrival
Morphine results in higher mortality
for NSTEMI patients
Due to blocking pain, yet ischemia still
present
Due to hypotension
Due to decreased myocardial perfusion
Many now use Fentanyl instead
Early Invasive Management Improves
Outcomes
NSTEMI- thus high risk patients in general do better if
treated aggressively in ED, then to cath lab in 4-24
hours. 18% death or MI reduction.
Even studies on stabilization and later treatment are
predicated on aggressive ED treatment
In general, this includes Clopidogrel, anticoagulant,
and Glycoprotein II B III A Inhibition
2007 Anti-platelet Guidelines
Nothing new on Aspirin- continue to use
Recommend Clopidogrel or II B III A
OR
Use both Clopidogrel and II B III A
Using both makes more scientific sense as
drugs work differently. Some patients are
partial or non-responders to Clopidogrel.
Anti-Platelet Therapy
 Clopidogrel is irreversible. Will delay CABG 3-5 days.
 Integrelin is reversible once infusion is shut off.
 Anti-platelet therapy is critical to success and is under-
utilized
 Coordinated, standard approach at your institution is
desirable.
 ISAR-REACT 2 study shows adding Glycoprotein IIBIIIA
The Central Role of the Platelet in
NSTE ACS
Sites of Antithrombotic Drug Action
Coagulation cascade
Platelet cascade
Intrinsic Pathway
Platelet Activation
Plasma clotting
cascade
LMWH
Prothrombin
Clopidogrel
Activation of
GP IIb-IIIa
Other
agonists
ADP
Factor
Xa
UFH
AT III*
Bivalirudin
Agonist
degranulation
TxA2
ASA
Platelet recruitment and aggregation
Thrombin
Fibrinogen cross links to form
platelet-rich thrombus
GP IIb-IIIa
inhibitors
Thrombolytics
Fibrin Mesh
Formation of
mature thrombus
*AT III = antithrombin III.
Stein B, et al. J Am Coll Cardiol. 1989;14(4):813-836; DeJong MJ, et al. Crit Care Nurs Clin N Am. 1999;11(3):355371; White HD. Am J Cardiol. 1997;80(4A):2B-10B.
The Role of the Platelet in Non-ST-segment
Elevation Acute Coronary Syndrome (NSTE ACS)
NSTE ACS is generally
caused by partially occlusive,
platelet-rich thrombus in a
coronary artery
Results from cross-linking of
platelets by fibrinogen at
platelet receptors GP IIb-IIIa
at site of plaque rupture
Unobstructed
lumen
GP IIb-IIIa
Platelet
Thrombus
Fibrinogen
Ruptured
plaque
Artery wall
Van de Werf F. Thromb Haemost. 1997;78(1):210-213; Moser M, et al. J Cardiovasc Pharmacol. 2003;41(4):
586-592; Reprinted with permission from Davies MJ. Heart. 2000;83(3):361-366. © BMJ Publishing Group Ltd. 2005.
The Thrombus in STEMI
STEMI is generally caused by a
completely occlusive fibrin-rich
thrombus in a coronary artery
Results from stabilization by fibrin
mesh of a platelet aggregate at
site of plaque rupture
platelet
RBC*
fibrin mesh
*RBC = red blood cell.
GP IIb-IIIa inhibitors are not indicated for STEMI.
Van de Werf F. Thromb Haemost. 1997;78(1):210-213; White HD. Am J Cardiol. 1997;80(4A):2B-10B;
Davies MJ. Heart. 2000;83(3):361-366.
Microembolization in Unstable Angina
Courtesy of C. Michael Gibson, MS, MD, Director TIMI Data Coordinating Center, Brigham & Women’s Hospital,
Associate Chief of Cardiology, Interventional Cardiologist, Beth Israel Deaconess Medical Center, Harvard
Medical School.
Variable Clopidogrel Response
Response measured after elective coronary artery stent implantation
At 5 Days
UA Patients* (n = 32)
At 4 Hours
Healthy Volunteers† (n = 25)
Nonresponders
16%
Nonresponders
22%
Responders
47%
Responders
72%
Low
responders
12%
Low responders
32%
*Received an oral loading dose of 300 mg of clopidogrel followed by 75 mg daily; †Received a 450-mg loading
dose of clopidogrel.
The use of clopidogrel in this study was not consistent with applicable FDA-approved Prescribing Information.
Gurbel PA, et al. Circulation. 2003;107(23):2908-2913; Lau WC, et al. Circulation. 2004;109(2):166-171.
GP IIb-IIIa Inhibitors Are an ACC/AHA
Guidelines IA Recommendation
AT PRESENTAION
HIGH-RISK FEATURES
 Signs of ischemia at rest > 20 minutes AND ST-segment depression and/or elevated cardiac biomarkers
RECOMMENDED TREATMENT REGIMEN
 Aspirin (IA); clopidogrel if aspirin is contraindicated (IA)
 LMWH or UFH (IA)
 GP IIb-IIIa inhibitor (IA)
 Beta blocker (IB)
 Nitrates (IC)
SEND FOR CATHETERIZATION & REVASCULARIZATION WITHIN 24-48 HOURS
PCI or CABG SURGERY IF CORONARY ANATOMY IS SUITABLE (IA)
CAUTIONARY INFORMATION
 No clopidogrel within 5-7 days prior to CABG surgery
 No enoxaparin within 24 hours prior to CABG surgery
 No abciximab, if PCI is not planned
LEVELS OF EVIDENCE
I. Evidence and/or agreement that treatment is effective
IIa. Weight of evidence favors use
IIb. Usefulness less well established
III. Evidence and/or agreement that treatment is not effective
Braunwald E, et al. J Am Coll Cardiol. 2002;40(7):1366-1374.
LEVELS OF EVIDENCE RANK
A. Based on large, randomized trials
B. Based on smaller trials or careful analyses
C. Based on expert consensus
Changes in Cardiac Arrest
Management
Pharmacology
 No improvements evident based on science with drugs
to improve outcome
 Epinephrine every 5 minutes
 No added benefit to Vasopressin
 Amiodarone and Lidocaine equal effectiveness
Defibrillation
 Primary treatment for V-fib at 3 minutes and under
 Should be delayed until good CPR for 2 minutes if down
time over 3 minutes
 Biphasic should be used
 AED’s good in 3 minutes, bad after
 One shock only with no pulse checks after
Vascular Access
 Avoid ET drugs whenever possible
 Peripheral IV’s OK
 Central IV’s slightly better, but compression interruption
frequent with placement
 Interosseous recommended when peripheral IV’s not
obtainable
Pathophysiology of V-Fib Arrest
How Compressions move blood
What about AED’s?
Great in first 3 minutes. Must be in community.
Deadly after this as delay to shock is over 30 seconds.
Manual defib required after 3 minutes.
Defibrillation
No more stacked shocks
Takes too long
All shocks maximum energy.
EMS probably should not use AED’s
Biphasic increases efficacy
Pulse Checks
Deadly!!
Only check pulses when rhythm appears to have
converted thru CPR on ECG or signs of life
ECC says check before shock delivered after 5 cycles
of 30:2 CPR
What about intubation?
In first 6 minutes, not a priority (V-fib) ASAP in PEA and
Asystole.
Understand that positive pressure breaths decrease
cardiac output.
Some air exchange from CPR plus gasping.
Once intubated, 1 second breaths,six per minute. NO
MORE.
Airway
Combitube or ET equivalent
RSA Mentality-view and see cords place
ET, otherwise immediate Combitube first
try.
Protocol
Dispatch instructs CCC
If good CPR on EMS arrival, shock max X1
If no or poor CPR, immediate compressions
Protocol
OP airway
Non-rebreather face mask @ 90+%
200 compressions
IV access
Epinephrine 1mg IVP
Vasopressin 40 units IVP ASAP
One shock, 3-5 seconds, no pulse checks.
Protocol
Begin second round of 200 compressions
Amiodarone 300mg IVP
Shock X1 at max joules
No pulse checks, not off chest more than 5 seconds.
Protocol
Begin 3rd round of compressions
Epinephrine 1mg IVP
Shock X1 after 200 compressions
Protocol
During 4th round of compressions place
definitive airway without halting compressions
on first attempt.
Protocol
200 compressions alternating epinephrine
with antidysrhythmic drug and shock X1.
Remain on scene and work until pulse or nonshockable rhythm.
48% Neuro-intact survivors!!
10% before new protocol
QUESTIONS??