Use of clopidogrel in the reduction of myocardial damage during percutaneous coronary intervention

Abstract

It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK)/creatinine kinase myocardial band (CK-MB) elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI). Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of clopidogrel is considered to be at least 300 mg given 6 to 15 hours prior to PCI but there is considerable evidence to suggest that a loading dose of 600 mg given 2 to 6 hours prior to PCI may be more efficacious in limiting post-coronary intervention events. The benefit obtained from clopidogrel appears independent of and incremental to that of other antiplatelet and antithrombotic agents used during and after coronary intervention.

Keywords: antiplatelet agents; clopidogrel; myocardial infarction; myonecrosis; percutaneous coronary intervention.

Figure 1

Kaplan Meier cumulative event rates for primary endpoint at 30 days after PCI in the PCI CURE study. Reprinted from The Lancet, 358, Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study, 527–533, Copyright © 2001, with permission from Elsevier.

Figure 2

CREDO combined end points at 28 Days. Reproduced with permission from Steinhubl et al. JAMA. 2002;288(19):2411–2420. Copyright © 2005 American Medical Association. All rights reserved.

Figure 3

Outcomes at 30 days in the PCI-CLARITY study. Reproduced with permission from Sabatine et al. JAMA. 2005;294(10):1224–1232. Copyright © 2005 American Medical Association. All rights reserved.

Figure 4

Summary of PCI studies assessing the effect of clopidogrel treatment. Reproduced with permission from Sabatine et al. JAMA. 2005;294(10):1224–1232. Copyright © 2005 American Medical Association. All rights reserved.

Figure 5

Meta-analysis of clopidogrel pretreatment in STEMI patients undergoing PCI with respect to short-term outcomes. Reproduced with permission from Vlaar PJ, Svilaas T, Damman K, et al. Impact of pretreatment with clopidogrel on initial patency and outcome in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review. Circulation. 2008;118(18):1828–1836. Copyright © 2008 Lippincott Williams and Wilkins.

Figure 6

Peri-procedural biomarker changes in the ARMYDA-2 study. Reproduced with permission from Patti G, Colonna G, Pasceri V, et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation. 2005;111(16):2099–2106. Copyright © 2005 Lippincott Williams and Wilkins.

Figure 7

Degree of platelet inhibition and major cardiovascular events. Reproduced with permission from 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(9):1742–1750. Copyright © 2006 Elsevier.

Figure 8

Effect of additional clopidogrel dosing on VASP Index. Reproduced with permission from 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(14):1404–1411. Copyright © 2008 Elsevier.

Figure 9

One month clinical outcomes standard versus VASP-guided clopidogrel loading. Reproduced with permission from 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(14):1404–1411. Copyright © 2008 Elsevier.