ReviewAspirin and Clopidogrel Resistance
Section snippets
ASPIRIN RESISTANCE
The term aspirin resistance has been used to describe the inability of aspirin to inhibit platelet aggregation as demonstrated by platelet function tests (eg, biochemical aspirin resistance).9 The term has also been used to describe the occurrence of CV events despite therapeutic aspirin intake (eg, clinical treatment failure). No consensus exists on whether the definition should be based on laboratory evidence, clinical outcomes, or both. The clinical importance of biochemical aspirin
MECHANISMS OF ASPIRIN RESISTANCE
The mechanisms of aspirin resistance are poorly understood and are likely to be multifactorial (Figure 2).27 Multiple factors affect platelet aggregation, including patient posture, time of day, exercise, and serum cholesterol levels.28 Additionally, cigarette smoking stimulates platelet aggregation and blunts the effect of aspirin.29 Moreover, drug-drug interactions may reduce the efficacy of aspirin. For example, nonsteroidal anti-inflammatory drugs block aspirin's access to the active site
THIENOPYRIDINES
The thienopyridines, clopidogrel and ticlopidine, irreversibly bind the platelet surface P2Y12 ADP receptor, thereby inhibiting ADP-induced platelet activation (Figure 1). Although ticlopidine has proven superiority to aspirin in the prevention of atherothrombosis,43 clopidogrel is more widely used than ticlopidine because it offers better safety and tolerability43 with similar efficacy.44
Patients who experience an ACS or undergo percutaneous coronary intervention (PCI) have a lower risk of
LABORATORY TOOLS TO SCREEN FOR EFFICACY OF ANTIPLATELET AGENTS
The most appropriate laboratory test for assessing aspirin and clopidogrel resistance has not yet been established.67 Four of the more common techniques for assessing platelet function include (1) bleeding time; (2) optical aggregometry, which measures platelet aggregation in plasma after exposure to substrates such as arachidonic acid, epinephrine, collagen, or ADP; (3) PFA-100 (Dade-Behring, Deerfield, Ill), which measures high shear stress-dependent platelet aggregation in whole blood; and
POTENTIAL ALTERNATIVES FOR THE ANTIPLATELET-RESISTANT PATIENT
One potential alternative or addition to aspirin or thienopyridine therapy is cilostazol, a phosphodiesterase 3 inhibitor approved for the treatment of intermittent claudication. In patients who have had a cerebrovascular event, cilostazol monotherapy significantly reduces the risk of recurrent stoke.70 The addition of cilostazol to aspirin or clopidogrel does not result in further bleeding time prolongation, suggesting safety of the combination therapy.71 In the Cilostazol for Restenosis Trial
CONCLUSION
Many issues remain unresolved regarding the definition, identification, and clinical importance of resistance to aspirin and clopidogrel. Given these limitations, no established consensus exists of whether aspirin- or clopidogrel-resistant patients should discontinue their antiplatelet regimen or whether additional therapy, such as cilostazol, should be added. Future studies will establish whether patients receiving antiplatelet agents should undergo platelet function studies to assess the
REFERENCES (77)
One hundred years of aspirin
Lancet
(1997)- et al.
Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment
J Am Coll Cardiol
(2004) - et al.
Profile and prevalence of aspirin resistance in patients with cardiovascular disease
Am J Cardiol
(2001) - et al.
A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease
J Am Coll Cardiol
(2003) - et al.
Incidence of aspirin nonresponsiveness using the Ultegra Rapid Platelet Function Assay-ASA
Am J Cardiol
(2003) - et al.
Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease
Thromb Res
(2002) - et al.
Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate
Thromb Res
(2002) - et al.
Aspirin resistance after coronary artery bypass grafting
J Thorac Cardiovasc Surg
(2001) - et al.
Two-year follow-up of aspirin responder and aspirin non-responder: a pilot-study including 180 post-stroke patients
Thromb Res
(1993) Aspirin resistance: more than just a laboratory curiosity
J Am Coll Cardiol
(2004)