哈佛医学院精品幻灯，GP IIb/IIIa抑制剂在UA/NSTEMI中的应用，共100张。
Dispelling the Myths: GP IIb/IIIa Inhibitors in UA/NSTEMI Management
Learning Objectives
Demonstrate the role of anti-platelet and anti-thrombin agents in the management of unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), including a review of the clinical benefits of the early use of GP IIb/IIIa inhibitors and their role in improving outcomes as well as their specific effects on high-risk UA/NSTEMI patients with diabetes
Explore the role of platelet-leukocyte conjugation in UA/NSTEMI
Discuss the presence of inflammatory biomarkers in patients with UA/NSTEMI
Review the ACC/AHA guidelines for GP IIb/IIIa use
ACC=American College of Cardiology.
AHA=American Heart Association.
Case Presentation: History and Exam
CC: Chest pain
HPI: 66-year-old woman presents to the ER complaining of several episodes of chest pain lasting 10-12 minutes each
PMH: Stable angina treated with PRN SL NTG; type 2 diabetes x 8 years managed with a sulfonylurea; hypercholesterolemia x 12 years managed with a statin; 40-pack-year smoker
Exam: Slightly overweight; BP 150/94 mm Hg; HR 78, regular
Evaluation: EKG - 1.5 mm ST-segment depression in precordial leads during chest pain episodes; troponin I level 2.1 ng/ml (nl <0.05 ng/ml)
Risk Stratification in UA/NSTEMI: TIMI Risk Score
Integrated risk predictor based on 7 variables:
Age ≥65 years
≥3 risk factors for CAD
Diabetes
Family history of CAD
Hypertension
Hypercholesterolemia
Current smoker
≥50% prior coronary stenosis
ST-segment deviation on EKG
At least 2 anginal events in prior 24 hours
Use of aspirin in prior 7 days
Elevated serum cardiac markers
Antman EM, et al. JAMA. 2000;284:835-842.
TIMI=Thrombolysis in Myocardial Infarction.
CAD=coronary artery disease.
This Patient Is High-Risk
≥3 risk factors for CAD
- Diabetes
- Hypertension
- Hypercholesterolemia
- Current smoker
Age ≥65 years
Elevated troponin I
ST-segment deviation
TIMI Score=5
>2 anginal events in past 24 hours
Braunwald E, et al. Circulation. 2002;106:1893-1900.
Overview of 2002 Update to the ACC/AHA Guidelines for UA/NSTEMI
Assess likelihood of CAD
Risk stratification
Target therapy: more aggressive treatment in higher-risk patients
Anti-ischemic, antithrombotic therapy
Invasive vs. conservative strategy
Discharge planning (risk-factor modification and long-term medical therapy)
Case Presentation: Plan of Action
A cardiologist is consulted and the patient is admitted at 10 pm; she is scheduled for an angiogram and possible PCI with stent insertion at 7 am the following morning
PCI=percutaneous coronary intervention.
How Would You Manage this Patient for the Next 9 Hours?
Antithrombotic Therapy Is Key to Maximizing Outcomes in UA/NSTEMI
There is confusion as to which agents to use and whether they are safe when used in combination
Therefore, it is important to address the misperceptions about the role of various antithrombotic agents in UA/NSTEMI management to improve patient outcomes
Rationale for Use: Pharmacologic Intervention in Thrombosis
UFH=unfractionated heparin.
LMWH=low-molecular-weight heparin
ADP=adenosine diphosphate.
TFPI=tissue factor pathway inhibitor
Selwyn A. Am J Cardiol. 2003;91:3H-11H.
Coagulation cascade
Platelets
LMWH
Thienopyridines
GP IIb/IIIa
inhibitors
Thrombolytics
LMWH
UFH
LMWH
UFH
Direct thrombin
inhibitors
Tissue factor
Factor Xa
Prothrombin
Thrombin
Platelets
A2 vWF ADP
Activated platelets
Fibrinogen cross-linking
Platelet aggregation
Aspirin
Fibrinogen
Fibrin
Fibrin
degradation
Collagen
Leukocytes
TFPI
Anti-thrombin
Anti-thrombin
Thromboxane
Plasmin
Thrombus
Myth #1: Aspirin plus an Anti-thrombin Agent Provide Sufficient Anticoagulation for Patients with UA/NSTEMI
Enoxaparin
1mg/kg q 12 H
Subcutaneous
+ aspirin
UFH Heparin
IV dose-adjusted
+ aspirin
Follow-up Visit
Day 14
Follow-up Visit
Day 14
Follow-up Call
Day 30
Follow-up Call
Day 30
Unstable Angina
Non-Q-Wave MI
Treatment Phase
min 48 hours, max 8 days
Follow-up Phase
MI=myocardial infarction.
Cohen M, et al. Am J Cardiol. 1998;82:19L-24L.
ESSENCE: Study Design
ESSENCE
Inclusion Criteria
Male or non-pregnant female ≥18 years of age
Recent-onset rest angina
Last episode of angina within 24 hours
Definite evidence of underlying CAD (1 or more):
Ischemic EKG changes on presentation
Previous MI, PTCA, or CABG
Previous angiography with >50% vessel stenosis
Exclusion Criteria
LBBB or pacemaker
Persistent ST-segment elevation
Angina precipitated by secondary causes (e.g., tachydysrhythmia, etc.)
Contraindication to anticoagulation
CrCl <30 mL/min
Cohen M, et al. Am J Cardiol. 1998;82:19L-24L.
LBBB=left bundle branch block.
PTCA=percutaneous transluminal coronary angioplasty.
CABG=coronary artery bypass graft.
CrCl=creatinine clearance.
Time (Days)
All Randomized Population
30%
25%
20%
15%
10%
5%
0
% of Patients with Death, MI, or Recurrent Angina
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31
Heparin
Enoxaparin
Death, MI, Recurrent Angina
Cohen M, et al. Am J Cardiol. 1998;82:19L-24L.
ESSENCE: First 30 Days, Enoxaparin Is Superior to UFH
Primary endpoint: Death or MI at 30 days
High-Risk NSTEMI Patients
Randomize (n=10,000)
Early invasive strategy
Other therapy per AHA/ACC guidelines
(aspirin, ?-blocker, ACE-I, clopidogrel, GP IIb/IIIa)
60 U/kg ? 12 U/kg/hr (aPTT 50–70 sec)
1 mg/kg SC Q12H
SYNERGY: Enoxaparin with Early Invasive Strategy in High-Risk UA/NSTEMI Patients
Enoxaparin
IV Heparin
At least 2 of 3 required:
Age ≥60
ST ? (transient) or ?
(+) CK-MB or Troponin
SYNERGY Trial Investigators. JAMA. 2004;292:45-54.
ACE-I=angiotensin-converting enzyme inhibitor.
Enoxaparin UFH (n=4,993) (n=4,985)
Median age (years) 68 68
Female sex (%) 34 34
Hypertension (%) 68 68
Diabetes (%) 29 30
Hypercholesterolemia (%) 58 59
Family history of CAD (%) 46 45
MI (%) 29 28
CHF (%) 9 9
Stroke (%) 5 5
PVD (%) 10 10
CABG (%) 16 17
PCI (%) 21 19
SYNERGY Trial Investigators. JAMA. 2004;292:45-54.
CHF=congestive heart failure.
PVD=peripheral vascular disease.
SYNERGY: A High-Risk Population
0
5
10
15
20
25
30
0.8
0.85
0.9
0.95
1.0
Freedom from Death/MI
Days from Randomization
UFH
Enoxaparin
SYNERGY: Enoxaparin and UFH Had Similar Reductions in 30-day Endpoint
SYNERGY Trial Investigators. JAMA. 2004;292:45-54.
Summary
ESSENCE and SYNERGY prove that enoxaparin is a viable alternative to upstream use of UFH in high-risk patients with UA/NSTEMI
Benefits of LMWHs:
Do not require continuous infusion
Do not require monitoring of aPTT
No effects on increasing surface GP IIb/IIIa receptors
ESSENCE: No GP IIb/IIIa inhibitors were used and most patients did not undergo early catheterization
SYNERGY did not show that enoxaparin can be used instead of an antiplatelet agent, but rather that it can be used as a complementary agent
More than half of patients received GP IIb/IIIa inhibitors
Almost all patients underwent early catheterization
SYNERGY showed increased bleeding with enoxaparin
High-risk patients d