LOWERING OF HDL(2B) BY PROBUCOL PARTLY EXPLAINS THE FAILURE OF THE DRUG TO AFFECT FEMORAL ATHEROSCLEROSIS IN SUBJECTS WITH HYPERCHOLESTEROLEMIA - A PROBUCOL QUANTITATIVE REGRESSION SWEDISH TRIAL (PQRST) REPORT

The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303) was to investigate whether probucol (0.5 g BID) added to die t and cholestyramine (8 g BID) could retard progression or induce regr ession of femoral atherosclerosis in hypercholesterolemic ( > 6.86 mmo l/L) subjects. Probucol did not induce regression over the 3-year tria l period as estimated by change in lumen volume on quantitative arteri ography of a 20-cm segment of the femoral artery. In this report we st udied in a representative subgroup (n = 72) whether the reduction in H DL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL par ticle size subclasses. Probucol lowered the relative level of HDL(2b), comprising the largest HDL particles, by 53% and the protein concentr ation of HDL(2b) by 67%. The protein reduction in HDL was mainly confi ned to the apolipoprotein A-I moiety. The change in lumen volume corre lated significantly with change in HDL, ie, HDL cholesterol (r = .34, P < .01), HDL(2) cholesterol (r = .37, P < .01), HDL(2b) protein (r = .44, P < .001), and the relative HDL(2b) value (r = .51, P < .001). Th e corresponding values for relative HDL(2b) distribution calculated on the active (n = 35) and placebo (n = 37) groups separately were also significant (r = .39 and .32, respectively; both P < .05). The correla tion between drug-induced change in the relative HDL(2b) concentration and change in atherosclerosis was independent of the alteration in tr iglyceride concentration and could not be explained by treatment inter action. HDL(2b) lowering was highly significantly correlated to probuc ol concentration. We suggest that the lowering effects of probucol on HDL and particularly on the HDL(2b) fraction at least in part explain why regression of femoral atherosclerosis was not obtained by the drug .