Clopidogrel Cilostazol

Comerota AJ. Effect on platelet function of cilostazol, clopidogrel, and aspirin, each alone or in combination. Atheroscler (suppl) 2006 6 13-19. 

CILOSTAZOL CLOPIDOGREL, DIPYRIDAMOLE, GLYCOPROTEIN lib/ Ilia INHIBITORS Possible t risk of bleeding with cilostazol Additive effect cilostazol has antiplatelet activity. Clopidogrel t the levels of a metabolite of cilostazol that has high antiplatelet activity, by an uncertain mechanism Warn the patient to report any signs of t bleeding... 

Clinically important, potentially hazardous interactions with abciximab, anagrelide, anticoagulants, cilostazol, clopidogrel, dabigatran, dipyridamole, eptifibatide, salicylates, ticlopidine, tirofiban. Many herbals that possess anticoagulant or antiplatelet activity... 

Cilostazol is a PDE3 inhibitor and also is a drug with multiple mechanisms of action (23,24), some of which are directly platelet-related, and others of which exert their effects indirectly via endothelial cells (Figs, 4 and 5), As a PDE inhibitor, it increases the concentration of cyclic nucleotides within platelets and inhibits platelet aggregation in response to shear forces (via ADP) and a variety of agonists. Like other inhibitors of platelet activation, it blocks the expression and release of P-selectin, a key adhesion molecule on the membrane of platelet alpha granules that externalizes with activation, and plays an important role in the interactions between platelets, endothelial cells, and leukocytes, The effect of cilostazol on P-selectin expression appears to be additive to those of aspirin and clopidogrel (25). 

Lee et al. (50) examined the clinical effect of triple antiplatelet therapy with cilostazol (200 mg load, 100 mg BID), aspirin, and athienopyridine (ticlopidine or clopidogrel) versus... 

Ahn JC, Song WH, Kwon JA, et al. Effects of cilostazol on platelet activation in coronary stenting patients who already treated with aspirin and clopidogrel. Korean J Int Med 2004 19 230-236. 

Cilostazol is a phosphodiesterase inhibitor that reduces platelet aggregation, vascular smooth muscle proliferation and also has vasodilatory effects. Earlier studies comparing cilostazol and aspirin to ticlodipine and aspirin identified no significant increase in the subacute stent thrombosis rate (21-23). Indeed, the latter has been supported by comparison of this combination to clopidogrel and aspirin (24). Two recent trials, however, have demonstrated that a much higher proportion of patients develop subacute stent thrombosis when taking cilostazol as compared with ticlodipine (25,26). The data from these trials are summarized in Table I. 

T ble 1 A comparison of the rates of subacute stent thrombosis in trials comparing cilostazol with ticlodipine or clopidogrel... 

Lee SW, Park SW, Hong MK, et al, Comparison of cilostazol and clopidogrel after successful coronary stenting. Am J Cardiol 2005 95(7) 859-862. 

There is an increased risk of bleeding if clopidogrel is given with aspirin, but the use of low-dose aspirin and clopidogrel can be beneficial. Ticlopidine increases the antia r ant effects of aspirin and there is an increased risk of bleeding on concurrent use. Cilostazol appears not to interact to a clinically relevant extent with low-dose aspirin, and the addition of dipyridamole to aspirin does not appear to increase the incidence of bleeding. 

In one study clopidogrel slightly increased levels of cilostazol, without altering platelet count, aPTT, or prothrombin time. However, the effect of concurrent use on bleeding time was not assessed. 

The concurrent use of cilostazol 150 mg twice daily and clopidogrel 75 mg daily for 5 days increased the AUC of cilostazol by only 9%, but increased the AUC of the dehydro metabolite of cilostazol by 24% (this metabolite has 3 to 4 times the potency of cilostazol in inhibiting platelet aggregation). No changes in platelet count, prothrombin time or aPTT were seen. However, clopidogrel alone prolonged bleeding time, and it was not possible to determine whether there was an additive effect with cilostazol. ... 

Amna, D., and M.U. Naidu. 2007. Pharmacod)mamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br. J. Clin. Pharmacol. 63(3) 333-338. Bal Dit Sollier, C., H. Caplain, and L. Drouet. 2003. No alteration in platelet function or coagulation induced by EGb761 in a controlled study. Clin. Lab. Haematol. 25(4) 251-253. Baron-Ruppert, G., and N.P. Luepke. 2001. Evidence for toxic effects of alkylphenols from Ginkgo biloba in the hen s egg test (HET). Phytomedicine 8(2) 133-138. 

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