Nifedipine in the treatment of Raynaud's phenomenon. Evidence for inhibition of platelet activation.
Platelet activation has been reported to occur in patients with Raynaud's phenomenon; however, the effect of calcium channel blockers and thromboxane synthetase inhibitors has not been previously studied. The effect of two drugs that potentially inhibit platelet activation were studied: nifedipine, a calcium channel blocker, and dazoxiben, a specific thromboxane synthetase inhibitor. Two platelet-specific proteins released during platelet activation, beta-thromboglobulin and platelet factor 4, were measured during a double-blind clinical trial of these two drugs in patients with Raynaud's phenomenon. The plasma beta-thromboglobulin level was significantly elevated in the patient population (53.8 +/- 7.6 ng/ml) during the placebo period compared with that in a normal control population (27.0 +/- 3.1 ng/ml) (p less than 0.01). The plasma platelet factor 4 level was 8.7 +/- 2.2 ng/ml in the patients compared with 6.5 +/- 1.0 ng/ml in the normal subjects (p = NS). These findings indicate the presence of in vivo platelet activation in patients with Raynaud's phenomenon. Nifedipine lowered the levels of beta-thromboglobulin to near the normal range (33.4 +/- 4.6 ng/ml). The inhibition of platelet activation by nifedipine was associated with clinical improvement in Raynaud's phenomenon with fewer and less intense episodes. Beta-thromboglobulin was not lowered by dazoxiben (58.1 +/- 9.0 ng/ml) compared with the placebo. The reduction of beta-thromboglobulin levels by nifedipine indicates that in vivo platelet activation was inhibited by this agent. Since this was associated with a reduced frequency of attacks, it is not clear whether this was a direct effect of the drug on platelet activation, leading to decreased frequency of vasospasm, or an effect on vascular smooth muscle leading to decreased vasospasm and a secondary decrease in platelet activation.
Malamet
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R
Wise
R A
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Ettinger
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Wigley
F M
FM
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D010919:Placebos; D010978:Platelet Factor 4 / Q000032:analysis; D011928:Raynaud Disease / Q000097:blood / Q000188:drug therapy*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D001620:beta-Thromboglobulin / Q000032:analysis
D001095:Arachidonic Acids; D007093:Imidazoles; D010919:Placebos; D001620:beta-Thromboglobulin; C029166:dazoxiben; D016718:Arachidonic Acid; D010978:Platelet Factor 4; D013930:Thromboxane-A Synthase; D009543:Nifedipine