+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status



Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status



Catheterization and Cardiovascular Interventions 81(1): 42-49



In patients on dual antiplatelet therapy with aspirin and clopidogrel, the adjunctive use of cilostazol is associated with enhanced platelet inhibition. However, if cilostazol exerts different pharmacodynamic (PD) effects according to levels of on-treatment platelet reactivity remains unknown. This study aimed to determine the PD effects of cilostazol in patients with and without high on-clopidogrel platelet reactivity (HPR) according to diabetes mellitus (DM) status. This is a post-hoc analysis derived from patients (n = 79) enrolled in a prospective, randomized, double-blind, double-dummy, crossover study comparing cilostazol with placebo in stable coronary artery disease patients on aspirin and clopidogrel therapy. In the present analysis, patients were divided according to the presence or absence of HPR (HPR and non-HPR). HPR was defined as a P2Y12 units (PRU) > 240 as assessed by the VerifyNow P2Y12 assay. The PD effects of cilostazol were evaluated in patients with and without HPR according to DM status. Significant absolute changes in PRU values were observed after adjunctive cilostazol in both HPR [53.4 (95% CI 24.7-82.1), P = 0.001] and non-HPR [40.8 (95% CI 28.7-52.8), P < 0.0001] patients. This difference was statistically significant in HPR patients with DM (P = 0.001), but not without DM (P = 0.24), and in non-HPR patients with and without DM (P = 0.0001 for both). The greatest mean reduction in PRU was observed in HPR patients with DM (72.9; 95% CI 33.7-112.0). Thrombin generation was not affected by cilostazol, irrespective of HPR status. Cilostazol reduces platelet reactivity both in HPR and non-HPR patients, although these PD effects are enhanced in HPR patients with DM. Nevertheless, larger studies are needed to better evaluate possible differential effects of cilostazol on platelet reactivity by diabetes status.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036406612

Download citation: RISBibTeXText

PMID: 22431415

DOI: 10.1002/ccd.24416


Related references

A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study. European Heart Journal 29(18): 2202-2211, 2008

Pharmacodynamic effects of atorvastatin vs. rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy. European Heart Journal 34(Suppl 1): P4849-P4849, 2013

Comparison of the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in stable patients with coronary artery disease treated with dual antiplatelet therapy : The ROMAN (RanOlazine vs. aMlodipine on platelet reactivity in stable patients with CAD treated with dual ANtiplatelet therapy) study. Journal of Thrombosis and Thrombolysis 40(3): 331-339, 2015

Comparison of on-treatment platelet reactivity between triple antiplatelet therapy with cilostazol and standard dual antiplatelet therapy in patients undergoing coronary interventions: a meta-analysis. Journal of Cardiovascular Pharmacology and Therapeutics 18(6): 533-543, 2013

Pharmacodynamic effects of atorvastatin versus rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy--the PEARL randomized cross-over study. European Journal of Pharmacology 725: 18-22, 2014

Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. Journal of the American College of Cardiology 55(11): 1139-1146, 2010

Impact of pentoxifylline on platelet function profiles in patients with type 2 diabetes mellitus and coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Jacc. Cardiovascular Interventions 4(8): 905-912, 2011

Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivity in patients with coronary artery disease treated with dual antiplatelet therapy. European Heart Journal 34(Suppl 1): P4915-P4915, 2013

Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivity in patients with coronary artery disease treated with dual antiplatelet therapy. Circulation Journal 78(3): 679-684, 2014

Interaction analysis between genetic polymorphisms and pharmacodynamic effect in patients treated with adjunctive cilostazol to dual antiplatelet therapy: results of the ACCEL-TRIPLE (Accelerated Platelet Inhibition by Triple Antiplatelet Therapy According to Gene Polymorphism) study. British Journal of Clinical Pharmacology 73(4): 629-640, 2012

Pharmacodynamic effects of adjunctive high dose atorvastatin on double dose clopidogrel in patients with high on-treatment platelet reactivity depending on diabetes mellitus status. Journal of Thrombosis and Thrombolysis 37(4): 427-434, 2014

Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy. Thrombosis and Haemostasis 106(2): 253-262, 2011

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial. European Heart Journal 32(7): 838-846, 2011

Association between High Platelet Reactivity Following Dual Antiplatelet Therapy and Ischemic Events in Japanese Patients with Coronary Artery Disease Undergoing Stent Implantation. Journal of Atherosclerosis and Thrombosis 2019:, 2019

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation 134(11): 780-792, 2016