A pharmacodynamic study of clopidogrel in chronic hemodialysis patients.

Combination antiplatelet agents, particularly aspirin and ticlopidine, have found increased use in the prevention of arterial thrombosis. Clopidogrel, a thienopyridine derivative, like ticlopidine was recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of ischemic events in patients with myocardial infarction, stroke, or peripheral arterial disease and appears to have much less hematologic toxicity than ticlopidine has. Thrombosis of hemodialysis access grafts is a major cause of morbidity in this patient population. Combination antiplatelet agents may be particularly useful in the prevention of hemodialysis access graft thrombosis. In preparation for such a study, we have performed a pharmacodynamic study of the platelet inhibitory effects of clopidogrel in patients on maintenance hemodialysis. Nine chronic hemodialysis patients were studied. Baseline platelet aggregation studies were performed, after which the subjects were begun on clopidogrel 75 mg daily. Platelet aggregation studies were repeated after 14 days of therapy. Drug was stopped and a final set of platelet aggregation studies were performed 7 days later. Because clopidogrel acts by inhibiting adenosine diphosphate (ADP)-induced platelet aggregation, we used ADP as the agonist in the platelet aggregation studies. We also measured the time required to achieve hemostasis after removing the dialysis needles at the termination of a dialysis session. Patients were carefully monitored for any adverse reaction to clopidogrel. Fourteen days' treatment with clopidogrel inhibited ADP-induced platelet aggregation from 48 to 23% with ADP 2 microM (P=0.0113), from 59 to 38% with ADP 5 microM (P=0. 0166), and from 66 to 44% with ADP 10 microM (P=0. 0172). This inhibition of platelet aggregation was reversed 7 days after stopping clopidogrel. Clopidogrel administration did not affect the time required to achieve hemostasis after removal of the dialysis needles. No adverse reactions were noted. No patient had evidence of bleeding, rash or gastro-intestinal (GI) upset. Clopidogrel inhibits ADP-induced platelet aggregation in subjects receiving chronic maintenance hemodialysis. The magnitude of inhibition is similar to that reported in nonuremic subjects with atherosclerosis. This inhibition is reversible within 7 days of discontinuing the drug. No adverse reactions to the drug were noted in this short-term (14-day) trial.

Alpha-tocopherol: effect on plasma lipoproteins in hypercholesterolemic patients.

This study was designed to examine the hypothesis that dl-alpha-tocopheryl acetate (vitamin E) increases the level of high-density lipoprotein cholesterol (HDLC) with a concomitant decrease of the ratio of total cholesterol/HDLC and a resultant amelioration of the coronary risk profile. Vitamin E (500 IU/day) or placebo were administered under double-blind randomized allocation to 69 hypercholesterolemic patients for 3 months. Sixty patients completed the study (30 in the active treatment group and 30 in the placebo group). Vitamin E raised the mean level of HDLC from 1.39 +/- 0.38 (SD) to 1.58 +/- 0.41 mmol, a 13.6% increase. This increase significantly (P less than 0.05) exceeded a parallel smaller increase of only 0.05 mmol (3.8%) in the placebo group. As total cholesterol (TC) declined by similar proportions in the vitamin E (7.8%) and placebo (9.4%) groups, a concomitant reduction of 23% in the TC/HDLC ratio was achieved in the vitamin E group, significantly exceeding a 9.1% reduction under placebo. Significant beneficial effects were noted on apolipoprotein (Apo) A (which rose) and Apo B (which declined). An increase of Apo A/Apo B ratio by 17.9% was observed only in the vitamin E group. These results suggest that the oral administration of vitamin E (500 IU/day) is beneficial in hyperlipoproteinemia and offers a potential tool for treating the increased coronary heart disease risk.

[Alpha blockers and microcirculation (author's transl)]. / Alpha bloqueurs et microcirculation.

The new compounds such as Prazosin are antihypertensive agents. Their action on blood pressure are a consequence of a direct action on vascular smooth muscle with little or no effect on cardiac output. This action is very important to reduce total peripheral resistance. In our Vascular Laboratory, we study 14 patients treated by Prazosin. They were all studied by capillaroscopy, ultrasonic investigations and plethysmography. Since Prazosin is primarily an alpha receptor blocker, it might be expected to have an action in microcirculation and in vasospastic diseases. We don't find modifications of microcirculation in seven people treated for hypertensive disease. Among seven patients with Raynaud phenomenon, we have only a good result in one case (Buerger disease) and two cases with a little increase of the fingertips blood flow.