Probucol improves symptoms and reduces lipoprotein oxidation susceptibility in patients with Raynaud's phenomenon

Objective. Reactive oxygen species have been implicated in the pathogenesis of inflammatory and vascular disease. We have undertaken a controlled tria l to evaluate probucol, a synthetic antioxidant, as a potential therapy for Raynaud's phenomenon. Methods. The study cohort included patients with systemic sclerosis (SSc; n = 20), primary Raynaud's phenomenon (n = 15) or 'autoimmune Raynaud's' (n = 5). Patients were allocated to receive either probucol (500 mg daily) or nifedipine (20 mg daily) for 12 weeks. Clinical and biochemical variables a t baseline were compared with those at completion of treatment. Evaluation included assessment of Raynaud's attack frequency and severity by visual an alogue scale, measurement of low-density lipoprotein (LDL) oxidation lag ti me, and plasma concentrations of cholesterol, triglyceride, vitamin E and v itamin C. Results. There was a significant reduction of both the frequency and severi ty of Raynaud's attacks in the patients who received probucol, but not in t he control group. LDL oxidation lag time, reflecting in vitro susceptibilit y to oxidation, was also increased by probucol therapy and serum cholestero l levels were significantly reduced. Similar changes were observed in both SSc- and non-SSc-associated Raynaud's cases. Conclusion. These data suggest that probucol may be useful for the symptoma tic treatment of Raynaud's phenomenon and also reduces LDL oxidation suscep tibility. Since oxidized lipoproteins may mediate vascular damage in SSc, t he use of probucol could have additional disease-modifying benefits. Based upon the results of this pilot study, further evaluation of this novel form of therapy is warranted.