Monitoring the Antiplatelet Effect of Cilostazol with Light Transmission Aggregometer: Two Cases of Possible Cilostazol Resistance
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Background: Coronary artery disease is an important cause of death in adults and stent insertion is one of the treatment modalities. The most severe adverse effect of a stent insertion is the formation of a thrombus; therefore, antiplatelet agents are used. The addition of cilostazol to low-dose aspirin and clopidogrel results in a better antiplatelet effect. However, laboratory tests to monitor the effect of cilostazol are insufficient. Methods: We tested the inhibitory effect of cilostazol using maximal platelet aggregation in 20 healthy volunteers. Conditions for incubation and concentrations of cilostazol and prostaglandin E1 (PGE1) were established and aggregation was induced by 5´-adenosine diphosphate (ADP) and measured with light transmission aggregometry (LTA). Blood samples were incubated with 1 μM and 2 μM cilostazol for 10 minutes at room temperature, and 80 nM PGE1 was added and incubated for an additional 10 minutes. Aggregation was induced by ADP and reactivity was evaluated. Results: The average maximum aggregation (MA) was 58.1% at 1 μM cilostazol and 22.0% when PGE1 was added. The average MA was 42.8% when cilostazol concentration was increased to 2 μM and 21.2% when PGE1 was added. Average inhibition of aggregation at 1 μM cilostazol was not statistically significant (P=0.085), but was significant (P=0.004) at 2 μM cilostazol. Aggregation was not inhibited even with 2 μM cilostazol and PGE1 in 2 volunteers, which suggests possible resistance to cilostazol. Conclusions: We designed a method to monitor the effect of cilostazol using in vitro incubation with PGE1.
Abstract
Background: Coronary artery disease is an important cause of death in adults and stent insertion is one of the treatment modalities. The most severe adverse effect of a stent insertion is the formation of a thrombus; therefore, antiplatelet agents are used. The addition of cilostazol to low-dose aspirin and clopidogrel results in a better antiplatelet effect. However, laboratory tests to monitor the effect of cilostazol are insufficient. Methods: We tested the inhibitory effect of cilostazol using maximal platelet aggregation in 20 healthy volunteers. Conditions for incubation and concentrations of cilostazol and prostaglandin E1 (PGE1) were established and aggregation was induced by 5´-adenosine diphosphate (ADP) and measured with light transmission aggregometry (LTA). Blood samples were incubated with 1 μM and 2 μM cilostazol for 10 minutes at room temperature, and 80 nM PGE1 was added and incubated for an additional 10 minutes. Aggregation was induced by ADP and reactivity was evaluated. Results: The average maximum aggregation (MA) was 58.1% at 1 μM cilostazol and 22.0% when PGE1 was added. The average MA was 42.8% when cilostazol concentration was increased to 2 μM and 21.2% when PGE1 was added. Average inhibition of aggregation at 1 μM cilostazol was not statistically significant (P=0.085), but was significant (P=0.004) at 2 μM cilostazol. Aggregation was not inhibited even with 2 μM cilostazol and PGE1 in 2 volunteers, which suggests possible resistance to cilostazol. Conclusions: We designed a method to monitor the effect of cilostazol using in vitro incubation with PGE1.
참고문헌 (18)
- Sudo T, "Estimation of anti-platelet drugs on human platelet aggregation with a novel whole blood aggregometer by a screen filtration pressure method", Br J Pharmacol, 133, pp.1396~1404 (2001)
- Gum PA, "Profile and prevalence of aspirin resistance in patients with cardiovascular disease", Am J Cardiol, 88, pp.230~235 (2001)
- Gurbel PA, "Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity", Circulation, 107, pp.2908~2913 (2003)
- Lee SW, "Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE-Long trial)", Am J Cardiol, 100, pp.1103~1108 (2007)
- Yamamoto Y, "Effects of cilostazol, an antiplatelet agent, on axonal regeneration following nerve injury in diabetic rats", Eur J Pharmacol, 352, pp.171~178 (1998)
- Yamamoto H, "Evaluation of the antiplatelet effects of cilostazol, a phosphodiesterase 3 inhibitor, by VASP phosphorylation and platelet aggregation", Circ J, 72, pp.1844~1851 (2008)
- Russo I, "The activity of constitutive nitric oxide synthase is increased by the pathway cAMP", cAMP-activated protein kinase in human platelets. New insights into the antiaggregating effects of cAMP-elevating agents, 2004, pp.114, 265~273
- Bramer SL, "Cilostazol pharmacokinetics after single and multiple oral doses in healthy males and patients with intermittent claudication resulting from peripheral arterial disease", Clin Pharmacokinet, 37(Suppl 2), pp.1~11 (1999)
- Catella-Lawson F, "DeMarco S, Tour-nier B, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin", N Engl J Med, 345, pp.1809~1817 (2001)
- Csiszar A, "Oxidative stress-induced isoprostane formation may contribute to aspirin resistance in platelets", Prostaglandins Leukot Essent Fatty Acids, 66, pp.557~558 (2002)
- Szczeklik A, "Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia", Arterioscler Thromb Vasc Biol, 16, pp.948~954 (1996)
- Christiaens L, "Resistance to aspirin in vitro at rest and during exercise in patients with angiographically proven coronary artery disease", Thromb Res, 108, pp.115~119 (2002)
- Goto S, "Antiplatelet therapy after coronary intervention in Asia and Japan: the Asian perspective of antiplatelet intervention", Hamostaseologie, 29, pp.321~325 (2009)
- Uchiyama S, "The safety and efficacy of clopidogrel versus ticlopidine in Japanese stroke patients: combined results of two Phase III, multicenter, randomized clinical trials", J Neurol, 256, pp.888~897 (2009)
- Chan FK, "Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding", N Engl J Med, 352, pp.238~244 (2005)
- Bhatt DL, "ACCF", ACG, J Am Coll Cardiol, pp.2008, 52[DOI]
- Yamamoto T, "Thienopyridine and cilostazol are safer for gastroduodenal mucosa than low-dose aspirin--second report of endoscopic evaluation", Thromb Res, 125, pp.365~366 (2010)
- Jeong YH, "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, 53, pp.1101~1109 (2009)