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 prevlously studied. The effect of two drugs that potentially inhibit platelet activation were studied: nlfedipine, a calcium channel blocker, and dazoxiben, a specific thromboxane synthetase Inhibitor. Two platelet-specific proteins released during platelet activation, betathromboglobulin 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 <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.