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.
OBJECTIVE
Patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with non-diabetics following P2Y(12) receptor blockade. Whether inhibition of P2Y(12) signalling can be enhanced by adjunctive treatment with cilostazol in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of cilostazol in T2DM patients on standard aspirin and clopidogrel treatment.


RESULTS
This was a prospective, double-blind, double-dummy, placebo-controlled, randomized, cross-over platelet function study. T2DM patients on dual antiplatelet therapy were assigned to receive cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment assignments for another 14 days. Platelet function was performed at three time points: at baseline, 14 days after randomization, and 14 days after treatment cross-over. The P2Y(12) reactivity index, determined through flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein, was the primary endpoint measure. In addition to this flow cytometric evaluation, light transmittance aggregometry and VerifyNow testing were performed. A total of 25 T2DM patients were randomized; five patients discontinued treatment due to side effects. The P2Y(12) reactivity index was significantly lower following cilostazol treatment compared with placebo (36.3 +/- 20 vs. 59.9 +/- 16%; P = 0.0002). All other P2Y(12)-specific functional assessments showed enhanced inhibition of this signalling pathway following treatment with cilostazol.


CONCLUSIONS
Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y(12) signalling.
Angiolillo
Dominick J
DJ
Division of Cardiology, University of Florida College of Medicine at Shands Jacksonville, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Capranzano
Piera
P
Goto
Shinya
S
Aslam
Mohammed
M
Desai
Bhaloo
B
Charlton
Ronald K
RK
Suzuki
Yoshie
Y
Box
Lyndon C
LC
Shoemaker
Steven B
SB
Zenni
Martin M
MM
Guzman
Luis A
LA
Bass
Theodore A
TA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D000077407:Cilostazol; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D058925:Receptors, Purinergic P2Y12; D013777:Tetrazoles / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin