阿司匹林抵抗与临床预后
Daniel I. Simon, M.D.
Associate Director, Interventional Cardiology
Brigham and Women’s Hospital
Associate Professor of Medicine
Harvard Medical School
Boston, MA USA
ASA Resistance and Clinical Outcomes
ASA Resistance: Key Questions
Does a standardized definition exist?
Are there reliable tests to diagnose this phenomenon?
What are the possible mechanisms and future implications?
Does it have any clinical significance?
How do we manage patients with Aspirin resistance?
Established Platelet Function Tests
Harrison P. Br J Hematology 2000;111:733-744
Newer Platelet Function Tests
(PFA)-100 Whole blood + Primary Limited range-most pts
hemostasis after GP IIb/IIIa inhibitors have
(high shear closure times >300 sec, so may
adhes/aggreg) not be able to discern diff. Used to assay ADP antagonist
Clot Signature Whole blood + Adhesion, Large instrument for routine use
Analyzer aggregation and interpretation of results is
complex
Rapid platelet Whole blood + Aggregation GP IIb/IIa: baseline sample req.
function assay Clinical outcome data (GOLD)
Aspirin: AA-like agonist
Harrison P. Br J Hematology 2000;111:733-744
Mukherjee D & Moliterno DJ. Clin Pharmacokinet 2000;39(6): 445-458
Flow cytometry Whole blood - Platelet GP, Flexible & powerful. Requires
activation markers, specialized operator. Expensive
Platelet function
Assay Substrate Bedside Principle Comments
Prevalence of ASA Resistance
Gum PA et al. Am J Cardiol 2001;88:230-235
ASA-R: mean aggregation ≥70% with μM 10 ADP & ≥20% with 0.5 mg/ml AA
325 patients with stable CVD taking ASA 325 mg >7days
Wang JC et al. Amer J Cardiol 2003;92:1492-4
422 patients presenting to cardiac cath lab on ASA 81-325 mg >7d
Prevalence of Aspirin Resistance
23.4% Aspirin non-responsive
Accumetrics VerifyNow Aspirin
Definition: ARU > 550
Multivariate analysis: history of CAD associated with twice the odds of being ASA non-responder (odds ratio 2.09, 95% CI 1.189-3.411, p=0.009)
No association with gender, DM, smoking, ASA dose
Clinical Studies
ASA Resistance: Long-term Clinical Studies
Stroke1 1500 mg Plt Reactivity 24 m Stroke/MI/ 10-fold lower
(n=180) Vascular death risk in ASA responders
PVD2 100 mg Whole blood 18 m Arterial 87% higher risk (n=100) aggregometry Occlusion in ASA-R
CVD/CVA3 100 mg PFA-10 >60 m Recurrent CVA/ Recurrent CVA 34%
(n=53) TIA TIA ASA-R vs. 0% no
recurrent events
Subgroup 75-325 mg Urinary 11-dehydro 5 yrs MI/Stroke/ 1.8 times
HOPE4 TX B2 &nb