Platelet monitoring for PCI

Summary

Percutaneous coronary intervention (PCI) has significantly improved clinical outcomes in coronary artery disease patients. Since PCI is associated with platelet activation, antiplatelet therapy with aspirin, clopidogrel and GPIIb/IIIa inhibitors comprise the cornerstone strategy during and following PCI. The latter agents are arguably the most important drugs we administer to the patient with established coronary artery disease since they are specifically given to prevent the most catastrophic event, the formation of an occlusive arterial thrombus. Numerous clinical trials have confirmed the efficacy of antiplatelet therapy in attenuating recurrent ischaemic event occur-rence.

Despite the extensive use of antiplatelet therapies, ischaemic event occurrence such as post-procedural myocardial infarction and stent thrombosis still remains an important concern and highlights the need for improved treatment strategies. A major limitation of current treatment is the application of a “one size fits all” strategy advocated by the guidelines that completely ignores the evaluation of the individual antiplatelet response. Pharmacodynamic studies have revealed the limitations of aspirin and clopidogrel treatment that include response variability, and a high prevalence of antiplatelet non-responsiveness associated with significant risk for recurrent ischemic event occurrence. Thus, two major paradoxes in cardiovascular medicine today are: 1) despite the overwhelming evidence that platelet reactivity strongly influences the development of potentially catastrophic events including myocardial infarction and stent thrombosis in the PCI patient, no measurement is made in clinical practice to assess the presence of blood vulnerability (platelet reactivity) and 2) despite the overwhelming evidence that the effect of dual antiplatelet therapy with aspirin and P2Y₁₂ receptor blockers is variable, the guidelines largely recommend a uniform, “one size fits all” dosing of these agents in the PCI patient without any confirmation of an adequate antiplatelet effect.

Keywords

Platelets - percutaneous coronary intervention

• References

• 1 Gurbel PA, Bliden KP, Hayes KM, Tantry U. Platelet activation in myocardial ischemic syndromes. Expert Rev Cardiovasc Ther 2004; 2: 535-545.
• 2 Watala C. Blood platelet reactivity and its pharmacological modulation in (people with) diabetes mellitus. Curr Pharm Des 2005; 11: 2331-2365.
• 3 Ferroni P, Basili S, Davi G. Platelet activation, inflammatory mediators and hypercholesterolemia. Curr Vasc Pharmacol 2003; 1: 157-169.
• 4 Trip MD, Cats VM, van Capelle FJ, Vreeken J. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 1990; 322: 1549-1554.
• 5 Gurbel PA, Kereiakes DJ, Dalesandro MR. et al. Role of soluble and platelet-bound P-selectin in discriminating cardiac from noncardiac chest pain at presentation in the emergency department. Am Heart J 2000; 139: 320-328.
• 6 Yilmaz MB, Cihan G, Guray Y. et al. Role of mean platelet volume in triagging acute coronary syndromes. J Thromb Thrombolysis 2008; 26: 49-54.
• 7 Braunwald E, Angiolillo D, Bates E. et al. The problem of persistent platelet activation in acute coronary syndromes and following percutaneous coronaryintervention. Clin Cardiol 2008; 31: I17-120.
• 8 Samara WM, Gurbel PA. The role of platelet receptors and adhesion molecules in coronary artery disease. Coron Artery Dis 2003; 14: 65-79.
• 9 Bliden KP, DiChiara J, Tantry US. et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current anti-platelet therapy adequate?. J Am Coll Cardiol 2007; 49: 657-666.
• 10 Kabbani SS, Watkins MW, Ashikaga T. et al. Usefulness of platelet reactivity before percutaneous coronary intervention in determining cardiac risk one year later. Am J Cardiol 2003; 91: 876-878.
• 11 Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107: 2908-2913.
• 12 Michelson AD, Linden MD, Furman MI. et al. Evidence that pre-existent variability in platelet response to ADP accounts for ‘clopidogrel resistance’. J Thromb Haemost 2007; 5: 75-81.
• 13 Miyamoto S, Kawano H, Kudoh T. et al. Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention. Am J Cardiol 2005; 96: 71-73.
• 14 Gurbel PA, Bliden KP, Kreutz RP. et al. The link between heightened thrombogenicity and inflammation: pre-procedure characterization of the patient at high risk for recurrent events after stenting. Platelets 2009; 20: 97-104.
• 15 Tantry US, Bliden KP, Kreutz RP. et al. Transition to an Unstable Coronary Syndrome is Marked by Hypercoaguability, Platelet Activation, Heightened Platelet Reactivity, and Inflammation: Results of the Thrombotic RIsk Progression (TRIP) Study. J Am Coll Cardiol 2007; 49: 196A.
• 16 Gurbel PA, Bliden KP, Hayes KM. et al. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting. J Am Coll Cardiol 2005; 45: 1392-1396.
• 17 Gurbel PA, Tantry US. Clopidogrel resistance?. Thromb Res 2007; 120: 311-321.
• 18 Matetzky S, Shenkman B, Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
• 19 Samara WM, Bliden KP, Tantry US, Gurbel PA. The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res 2005; 115: 89.
• 20 Gurbel PA, Antonino MJ, Tantry US. Antiplatelet treatment of cardiovascular disease: a translational research perspective. Pol Arch Med Wewn 2008; 118: 289-297.
• 21 Gurbel PA, Bliden KP, Guyer K. et al. Platelet reactivity in patients and recurrent events post-stenting: Results of the PREPARE POST-STENTING study. J Am Coll Cardiol 2005; 46: 1820-1826.
• 22 Gurbel PA, Bliden KP, Zaman KA. et al. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: Results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation 2005; 111: 1153-1159.
• 23 Gurbel PA, Bliden KP, Tantry US. Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting: Results from the CLEAR PLATELETS 1b study. J Am Coll Cardiol 2006; 48: 2186-2191.
• 24 Gurbel PA, Bliden KP, Saucedo JF. et al. Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: Effects on platelet function, thrombelastographic indices and their relation to periprocedural infarction:Results of the CLEAR PLATELETS-2 study. J Am Coll Cardiol 2009; 53: 648-657.
• 25 Lev EI, Patel RT, Maresh KJ. et al. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: The role of dual drug resistance. J Am Coll Cardiol 2006; 47: 27-33.
• 26 Cuisset T, Frere C, Quilici J. et al. High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes. Thromb Haemost 2007; 97: 282-287.
• 27 Geisler T, Langer H, Wydymus M. et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 2006; 27: 2420-2425.
• 28 Hochholzer W, Trenk D, Bestehorn HP. et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006; 48: 1742-1750.
• 29 Frere C, Cuisset T, Quilici J. et al. ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome. Thromb Haemost 2007; 98: 838-843.
• 30 Price MJ, Endemann S, Gollapudi RR. et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008; 29: 992-1000.
• 31 Gurbel PA, Antonino MJ, Bliden KP. et al. Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: A potential antiplatelet therapeutic target. Platelets 2008; 19: 595-604.
• 32 Barragan P, Bouvier JL, Roquebert PO. et al. Resistance to thienopyridines: Clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003; 59: 295-302.
• 33 Gurbel PA, Bliden KP, Samara W. et al. The clopidogrel Resistance and Stent Thrombosis (CREST) study. J Am Coll Cardiol 2005; 46: 1827-1832.
• 34 Buonamici P, Marcucci R, Miglironi A. et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007; 49: 2312-2317.
• 35 Bonello L, Paganelli F, Arpin-Bornet M. et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 5: 1630-1636.
• 36 Cuisset T, Hamilos M, Sarma J. et al. Relation of low response to clopidogrel assessed with point-of-care assay to periprocedural myonecrosis in patients undergoing elective coronary stenting for stable an-gina pectoris. Am J Cardiol 2008; 101: 1700-1703.
• 37 Wang ZJ, Zhou YJ, Liu YY. et al. Impact of clopidogrel resistance on thrombotic events after percutaneous coronary intervention with drug-eluting stent. Thromb Res 2009; 124: 46-51.
• 38 Gori AM, Marcucci R, Migliorini A. et al. Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents. J Am Coll Cardiol 2008; 52: 734-739.
• 39 Marcucci R, Gori AM, Paniccia R. et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: A 12-month follow- up. Circulation 2009; 119: 237-342.
• 40 Bonello L, Camoin-Jau L, Arques S. et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: A multicenter randomized prospective study. J Am Coll Cardiol 2008; 51: 1404-1411.
• 41 Bonello ST, Bonello L, Camoin-Jau L. et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol 2009; 103: 5-10.
• 42 Valgimigli M, Campo G, de Cesare N. et al. Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study. Circulation 2009; 119: 3215-3222.
• 43 Patti G, Nusca A, Mangiacapra F. et al. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol. 2008; 52: 1128-1133.
• 44 Sibbing D, Braun S, Morath T. et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009; 53: 849-856.
• 45 Tantry US, Mahla E, Gurbel PA. Aspirin resistance. Progress in Cardiovascular Diseases 2009; 52: 141-152.
• 46 Gurbel PA, Bliden KP, DiChiara J. et al. Evaluation of dose-related effects of aspirin on platelet function: Results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation 2007; 115: 3156-3164.
• 47 DiChiara J, Bliden KP, Tantry US. et al. The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients: An analysis from the aspirin-induced platelet effect (ASPECT) study. Diabetes 2007; 56: 3014-3019.
• 48 Tantry US, Bliden KP, Gurbel PA. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol 2005; 46: 1705-1709.
• 49 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961-965.
• 50 Chen WH, Lee PY, Ng W. 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; 43: 1122-1126.
• 51 Chen WH, Cheng X, Lee PY. et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med 2007; 120: 631-635.
• 52 Gianetti J, Parri MS, Sbrana S. et al. Platelet activation predicts recurrent ischemic events after percutaneous coronary angioplasty: a 6 months prospective study. Thromb Res 2006; 118: 487-493.
• 53 Reny JL, De Moerloose P, Dauzat M, Fontana P. Use of the PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost 2008; 6: 444-450.
• 54 Chen KY, Rha SW, Li YJ. et al. Korea Acute Myocardial Infarction Registry Investigators. Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 2009; 119: 3207-3214.
• 55 Han Y, Li Y, Wang S. et al. Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J 2009; 157: 733-739.
• 56 Jeong YH, Lee SW, Choi BR. et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity: results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) randomized study. J Am Coll Cardiol 2009; 53: 1101-1109.
• 57 Duzenli MA, Ozdemir K, Aygul N. et al. Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin. Am J Cardiol 2008; 102: 396-400.
• 58 Steinhubl SR, Bhatt DL, Brennan DM. et al. CHARISMA Investigators. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med 2009; 150: 379-386.
• 59 Price MJ, Berger PB, Angiolillo DJ, Teirstein PS, Tanguay JF, Kandzari DE, Cannon CP, Topol EJ. Evaluation of individualized clopidogrel therapy after drug-eluting stent implantation in patients with high residual platelet reactivity: design and rationale of the GRAVITAS trial. Am Heart J 2009; 157: 818-824.
• 60 Mehta SR, Bassand JP, Chrolavicius S. et al. CURRENT-OASIS 7 Steering Committee. Design and rationale of CURRENT-OASIS 7: a randomized, 2 x 2 factorial trial evaluating optimal dosing strategies for clopidogrel and aspirin in patients with ST and non-ST-elevation acute coronary syndromes managed with an early invasive strategy. Am Heart J 2008; 156: 1080-1088.
• 61 Wiviott SD, Braunwald E, McCabe CH. et al. TRITON- TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
• 62 Vvan Giezen JJJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y₁₂ antagonists. Semin Thromb Hemost 2005; 31: 195-204.
• 63 Fox KA, Mehta SR, Peters R. et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation 2004; 110: 1202-1208.