Antiplatelet Therapy in Neuroendovascular Therapeutics

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Adhesion-activation-secretion-aggregation sequence

Platelets are anucleate blood cells with a tremendous capacity for interaction with their surrounding vascular environment. Platelets contain storage granules that hold multiple chemokines, cytokines, and growth factors. In addition, platelets can synthesize bioactive prostaglandins from membrane phospholipids.

In the resting state, the intact endothelium releases inhibitory factors, such as prostacyclin (PGI2) and nitric oxide (NO), which function to maintain platelets in a nonactivated state (

Mechanism of action

The initial activation of platelets results in the activation of phospholipase A2, leading to the liberation of arachidonic acid (AA) from membrane phospholipids. AA is immediately converted by cyclo-oxygenase (COX-1) to prostaglandin G2 (PGG2) and PGH2 and then to TXA2 by thromboxane synthase (TS). TXA2 is then released from the platelet to participate in a platelet receptor–mediated positive feedback loop, which plays a critical role in the further amplification of regional platelet

Measurement of antiplatelet activity

In neuroendovascular therapeutics, the ability to assess the status of platelet function rapidly and accurately is critical. Not infrequently, antiplatelet agents must be reversed immediately and completely to accommodate a required surgical intervention (eg, ventriculostomy catheter placement or craniotomy) or in response to a procedural hemorrhagic complication. Alternatively, given the frequency, and associated clinical implications, of antiplatelet agent resistance, adequate platelet

Anti-Thrombotic Trialists Collaboration

The most comprehensive summary of available data regarding the clinical efficacy of antiplatelet therapy comes from the Anti-Thrombotic Trialists Collaboration [48]. This study incorporated data from 287 studies (comprehensive through September 1997) involving 135,000 “high-risk” patients in comparisons of antiplatelet therapy versus controls. High-risk patients were those with acute or previous vascular disease or with significant risk factors for vascular disease. In these patients,

Applications of antiplatelet agents in interventional neuroradiology

There are no widely accepted antiplatelet regimens for application in common neuroendovascular scenarios. The agents selected and doses reported vary widely. Frequently, these decisions are based on individual operator experience and practice patterns rather than on an extrapolation of the existing data.

Summary

Our understanding of the pharmacology of antiplatelet therapy continues to evolve rapidly. Although the existing data are primarily generated in the setting of interventional and preventative cardiology studies, these data may be extrapolated to guide the rational application of these agents in neuroendovascular procedures. Platelet function testing represents an increasingly available and practical method by which to verify the adequacy of therapy and guide clinical decision making. The

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References (102)

  • F.J. Neumann et al.

    Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting

    J Am Coll Cardiol

    (2001)
  • N.S. Kleiman et al.

    Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors

    J Am Coll Cardiol

    (1995)
  • A.S. Kini et al.

    Effectiveness of tirofiban, eptifibatide, and abciximab in minimizing myocardial necrosis during percutaneous coronary intervention (TEAM pilot study)

    Am J Cardiol

    (2002)
  • Y.F. Li et al.

    Comparative efficacy of fibrinogen and platelet supplementation on the in vitro reversibility of competitive glycoprotein IIb/IIIa receptor-directed platelet inhibition

    Am Heart J

    (2002)
  • R.A. Harrington et al.

    Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention

    Am J Cardiol

    (1995)
  • D.L. Bhatt et al.

    Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. CAPRIE Investigators

    Am Heart J

    (2000)
  • S.R. Mehta et al.

    Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study

    Lancet

    (2001)
  • E.J. Topol et al.

    Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial

    Lancet

    (1999)
  • S.G. Ellis et al.

    Effect of 18- to 24-hour heparin administration for prevention of restenosis after uncomplicated coronary angioplasty

    Am Heart J

    (1989)
  • H.Z. Friedman et al.

    Randomized prospective evaluation of prolonged versus abbreviated intravenous heparin therapy after coronary angioplasty

    J Am Coll Cardiol

    (1994)
  • J. Owen et al.

    Thrombolytic therapy with tissue-plasminogen activator or streptokinase induces transient thrombin activity

    Blood

    (1988)
  • P.A. Merlini et al.

    Thrombin generation and activity during thrombolysis and concomitant heparin therapy in patients with acute myocardial infarction

    J Am Coll Cardiol

    (1995)
  • R.E. Baier et al.

    Initial events in interactions of blood with a foreign surface

    J Biomed Mater Res

    (1969)
  • C. Patrono

    Aspirin as an antiplatelet drug

    N Engl J Med

    (1994)
  • E.H. Awtry et al.

    Aspirin

    Circulation

    (2000)
  • M.J. Alberts et al.

    Antiplatelet effect of aspirin in patients with cerebrovascular disease

    Stroke

    (2004)
  • M.R. Mueller et al.

    Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty

    Thromb Haemost

    (1997)
  • M.J. Quinn et al.

    Ticlopidine and clopidogrel

    Circulation

    (1999)
  • M.E. Bertrand et al.

    Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS)

    Circulation

    (2000)
  • I. Muller et al.

    Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement

    Heart

    (2001)
  • CAPRIE Steering Committee

    A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE)

    Lancet

    (1996)
  • C. Patrono et al.

    Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European Society of Cardiology

    Eur Heart J

    (2004)
  • M. Savcic et al.

    Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects

    Semin Thromb Hemost

    (1999)
  • Y. Cadroy et al.

    Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans

    Circulation

    (2000)
  • C. Patrono

    Pharmacology of antiplatelet agents

  • S.R. Steinhubl et al.

    Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial

    JAMA

    (2002)
  • P.A. Gurbel et al.

    Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity

    Circulation

    (2003)
  • I. Muller et al.

    Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement

    Thromb Haemost

    (2003)
  • W.C. Lau et al.

    Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance

    Circulation

    (2004)
  • S. Matetzky et al.

    Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction

    Circulation

    (2004)
  • G.A. Fitzgerald

    Dipyridamole

    N Engl J Med

    (1987)
  • H. Tran et al.

    Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease

    JAMA

    (2004)
  • B.S. Coller

    Platelet GPIIb/IIIa antagonists: the first anti-integrin receptor therapeutics

    J Clin Invest

    (1997)
  • M. Gawaz et al.

    Evaluation of platelet membrane glycoproteins in coronary artery disease: consequences for diagnosis and therapy

    Circulation

    (1999)
  • ESPRIT Investigators

    Enhanced suppression of the platelet IIb/IIIa receptor with Integrilin therapy. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial

    Lancet

    (2000)
  • RESTORE Investigators

    Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis

    Circulation

    (1997)
  • S.C. Smith et al.

    ACC/AHA guidelines for percutaneous coronary intervention

    Circulation

    (2001)
  • The EPILOG Investigators

    Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization

    N Engl J Med

    (1997)
  • G. Renda et al.

    Effect of fibrinogen concentration and platelet count on the inhibitory effect of abciximab and tirofiban

    Thromb Haemost

    (2003)
  • S.R. Steinhubl et al.

    Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study

    Circulation

    (2001)

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