Acute coronary syndrome clopidogrel

Acute coronary syndrome For patients with acute coronary syndrome (unstable angina/non-Q-wave Ml) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or coronary artery bypass graft (CABG), clopidogrel has been shown to decrease the rate of a combined endpoint of cardiovascular death. Ml, or stroke, as well as the rate of a combined endpoint of cardiovascular death. Ml, stroke, or refractory ischemia. 

Budaj A, Yusuf S, Mehta SR, Eox KA, Tognoni G, Zhao E et al. Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups. Circulation 2002 106(13) 1622-6. 

In 45 patients with acute coronary syndrome randomized to receive either atorvastatin 10 mg/day or pravastatin 40 mg/day neither atorvastatin nor pravastatin significantly affected clopidogrel-induced inhibition of platelet activation nor did clopidogrel affect the therapeutic efficacy of atorvastatin (84). 

The inhibitory potency of clopidogrel on ADP-induced platelet activation was not attenuated when it was coadministered with atorvastatin (20 mg/day) for 5 weeks in 51 patients with acute coronary syndromes (86). Atorvastatin had no effect on either clopidogrel-induced inhibition of platelet aggregation initiated by ADP 5 or 10 pmol/l or clopidogrel-induced reduction of the membrane expression of P-selectin and CD40L induced by ADP. 

Mitsios JV, Papathanasiou AI, Rodis FI, Elisaf M, Goudevenos JA, Tselepis AD. Atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly for 5 weeks in patients with acute coronary syndromes. Circulation 2004 109(ll) 1335-8. 

I 6 Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment the ISAR-REACT 2 randomized trial. JAMA 2006 ... 

Clopidogrel inhibits platelet aggregation in a dose-dependent fashion, Several studies have shown that a loading dose of clopidogrel results in a much more rapid onset of platelet inhibition than that achieved by regular low doses (II), and recommended loading doses in acute coronary syndromes (ACS) management are 300 mg followed by 75 mg once daily. 

YusufS, Zhao F Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation, N Engl J Med 2001 345 494-502. 

Lindgren R Jonsson B, Yusuf S. Cost-effectiveness of clopidogrel in acute coronary syndromes in Sweden a long-term model based on the CURE trial. J Intern Med 2004 255 562-570. 

Xiao Z, Theroux R Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome. J Am Coll Cardiol 2004 43 1 982-1988. 

Di Nisio M, Bijsterveld NR, Meijers JC, Levi M, Buller HR, Peters RJ. Effects of clopidogrel on the rebound hypercoagula-ble state after heparin discontinuation in patients with acute coronary syndromes. J Am Coll Cardiol 2005 46 I 582-1583,... 

Wienbergen H, Gift AK, Schiele R, et al. MITRA PLUS Study Group. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003 92 285-288. 

In the CURE study, 12,562 patients with acute coronary syndromes without ST-segment elevation have received ASA and clopidogrel 300 mg bolus, followed by 75 mg daily, versus ASA and placebo (50). The clopidogrel group had early reduction [within 24 hours of treatment—9.3% vs. I 1.4%, RR reduction 20% (p < 0.001) in the primary endpoint death from cardiovascular cause, nonfatal Ml, or stroke], which was sustained at one year, and was observed in all patients with acute coronary syndromes regardless of their level of risk. CURE patients who underwent PCI and were randomized to clopidogrel had a 31% RR reduction in death and Ml compared with placebo-treated PCI patients (51). 

Peters R, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 2003 108 1682- 1687. 

Fig. 4 Proposed testing algorithm for clopidogrel therapy for acute coronary syndromes...

Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl JMed2007 357(20) 2001-15. 

Lincoff AM, Steinhubl SR, Manoukian SV, et al. Influence of timing of clopidogrel treatment on the efficacy and safety of bivalirudin in patients with non-ST-elevation acute coronary syndromes undergoing percutaneous coronary intervention. An analysis of the ACUITY Trial. JACC Cardiovasc Interv 2008 l(6) 639-48. 

Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009 301(9) 934-944. 

ADP, thromboxane A2, fibrin, and serotonin. Prostacyclin (PGI2) from endothelial cells and cAMP are naturally occurring compounds that inhibit platelet aggregation. Clopidogrel and ticlopi-dine are antagonists of ADP that are used both in acute coronary syndromes and as alternatives to ASA for prophylaxis post-MI and for transient ischemic attacks (TLAs). 

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