Background-After treatment with clopidogrel, patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with patients who are not diabetic. Whether platelet inhibition can be enhanced by increasing clopidogrel maintenance dosage in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of a high maintenance dose in T2DM patients with suboptimal clopidogrel-induced antiplatelet effects. Methods and Results-T2DM patients on chronic dual antiplatelet therapy were screened to identify suboptimal clopidogrel responders. The latter were randomized to 30-day treatment with a standard (75 mg; nϭ20) or high (150 mg; nϭ20) daily maintenance dose. Platelet function was assessed at 3 time points: baseline, 30 days after randomization, and 30 days after resuming standard dosing. Platelet function parameters included adenosine diphosphate-induced (20 and 5 mol/L) maximal and late platelet aggregation, inhibition of platelet aggregation, platelet disaggregation, and P2Y 12 reactivity index. A total of 64 T2DM patients were screened to identify 40 suboptimal responders. After randomization, maximal adenosine diphosphate-induced (20 mol/L) platelet aggregation was significantly reduced in the 150-mg group compared with the 75-mg group (Pϭ0.002; primary end point). However, suboptimal clopidogrel response was still present in 60% of patients on the 150-mg regimen. All other platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects with 150 mg, which returned to baseline values after resumption of standard dosing. Conclusions-A 150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects compared with 75 mg in high-risk T2DM patients. However, enhanced ex vivo platelet reactivity continues to persist, the clinical implications of which are unknown and need to be evaluated in large-scale clinical trials. (Circulation. 2007;115:708-716.)

Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y(12) signalling.

Background-A drug interaction between clopidogrel and omeprazole resulting in impaired platelet inhibition has been reported. It has been suggested that staggering administration of clopidogrel and omeprazole may overcome this pharmacodynamic (PD) interaction. Methods and Results-This prospective, open-label, 3-period, randomized crossover study was performed in 20 healthy volunteers. Subjects were randomly selected to receive omeprazole (40 mg daily) concomitantly (CONC) or staggered by 8 to 12 hours (STAG) for 1 week on a background of clopidogrel therapy in a crossover fashion, with a 2-to 4-week washout period between treatments. After another 2-to 4-week washout period, all subjects were treated for 1 week with clopidogrel alone. Clopidogrel was administered as a 600-mg loading dose followed by a 75-mg maintenance dose during all phases. PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, VerifyNow P2Y 12 system, and light transmittance aggregometry at baseline, 24 hours, and 1 week.

T-lymphocyte subsets when measured in steroid responsive nephrotic syndrome (SRNS) have demonstrated significant variance from normal values. T-cell subsets were studied by using two-color flow cytometric analysis in 32 children (9.2 +/- 5 years of age) with SRNS. The children were divided into four groups: a) SRNS in acute relapse, on prednisone; b) SRNS in acute relapse, off prednisone; c) SRNS in long-term remission, off prednisone (nephrotic controls); d) patients in remission on long-term prednisone therapy; and e) 15 age-matched normal controls. Children suffering an acute relapse of SRNS showed an increase in Leu2a+/DR+ (CD8) activated lymphocytes (P less than 0.05), a decrease in Leu4a+ total T-lymphocytes (P = 0.01) and a decrease in Leu3a+ (CD4) helper T-cells (P less than 0.05) when compared to normal controls and nephrotic controls. Though some subset changes may represent a prednisone effect and the functional role of these lymphocytes in the disease process is unknown, this study provides additional evidence to support a role for abnormal T-cell subsets in the etiology of SRNS.

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