Cytoplasmic free calcium mobilization in platelets, expression of P-selectin, phosphatidylserine, and microparticle formation, measured by whole blood flow cytometry, in hypertensive patients. Effect of doxazosin GITS

The effects of doxazosin on expression of CD62 (P-selectin) and phosphatidylserine on platelet membrane and platelet calcium flux were studied in 50 uncomplicated essential hypertensive patients (World Health Organization stages 1-2) and 80 normotensive control subjects, matched for age, sex, and cardiovascular risk factors. Hypertensive patients showed greater in vivo platelet activation at baseline than control patients (percentage of CD62-positive platelets, 4.1+/-2.2% versus 2.4+/-1.5%, p<0.001; percentage of phosphatidylserine-positive platelets, 0.8+/-0.5% versus 0.5+/-0.3%, p<0.001). Increased platelet activation was associated with significant changes in the mobilization of free intraplatelet calcium, evaluated by a whole blood flow cytometric kinetic method. With this method, an arbitrary Ca(2+) mobilization index was defined as the ratio of cytoplasmic free calcium before activation with thrombin to the slope of the calcium removal rate following the action of the agonist. This index was significantly higher in untreated hypertensive patients than in normotensive controls (0.12+/-0.06 versus 0.05+/-0.08, p<0.001). Treatment of hypertensive patients with doxazosin gastrointestinal therapeutic system (4 mg/day as a single dose) for 2 months normalized both platelet activation and Ca(2+) mobilization. Changes in the expression of CD62 and phosphatidylserine in the platelet membrane after treatment with doxazosin gastrointestinal therapeutic system may be related to normalization of the kinetics of cytoplasmic free Ca(2+). Normalization of platelet activation may represent an additional beneficial effect to the known antihypertensive action of doxazosin gastrointestinal therapeutic system.     

The effect of clopidogrel besylate and clopidogrel hydrogensulfate on platelet aggregation in patients with coronary artery disease: a retrospective study

Background

Recently several alternative forms of the original clopidogrel hydrogensulfate (CHS) were spread worldwide. A large amount of such drugs turned out to be clopidogrel besylate (CB). Only three studies, involving healthy volunteers, investigated the antiplatelet effect of CB, whereas its attribute remained unexplored in the case of patients with cardiovascular diseases. This retrospective study aimed to evaluate the difference between the antiplatelet effects of two clopidogrel formulas, CHS and CB, on patients with coronary artery diseases.

Methods

Data of 150 patients with previous CHS treatment were investigated. According to the documentations, the CHS therapy was shifted to CB. 94 patients of the selected population received dual antiplatelet therapy, clopidogrel and aspirin. The antiplatelet effects of CHS and CB were compared by ADP induced platelet aggregation measurements using light transmission aggregometry.

Results

Irrespective of the therapeutic combinations the performed statistical investigations failed to show significant difference (p = 0.30) between the effect of CB (AGGmax_CB: 27.6 ± 13.7%) or CHS (AGGmax_CHS: 29.0 ± 15.3%) on the ADP induced platelet aggregation. Insignificant deviations were found in both forms of clopidogrel salts, either in the lack (AGGmax_CB : 32.5 ± 14,2%; AGGmax_CHS: 34,0 ± 16,1%; p = 0,29) or in the presence of aspirin (AGGmax_CB: 24.7 ± 12,5%; AGGmax_CHS: 26,0 ± 14,1%; p = 0,31).

Conclusion

Our results indicated that both CB and CHS had an identical inhibitory effect on ADP induced platelet aggregation in patients with cardiovascular diseases. Moreover their efficiency showed no overall significant difference in the case of dual antiplatelet therapy with aspirin as well. However there might be an inter- and intraindividual variability between the two clopidogrel formulas.