EFFECTS OF INTENSIVE LIPID-LOWERING THERAPY ON THE CORONARY-ARTERIES OF ASYMPTOMATIC SUBJECTS WITH ELEVATED APOLIPOPROTEIN-B

Background. Do the benefits of intensive lipid-lowering therapy seen i n symptomatic patients extend to high-risk subjects who have never had symptoms? Methods and Results. Of 120 men completing the FATS trial, 91 were symptomatic and 29 asymptomatic. All had apolipoprotein B grea ter than or equal to 125 mg/dL, a positive family history, and coronar y atherosclerosis. All were counseled in diet and randomized to intens ive therapy: colestipol 10 g TID plus either niacin 1 g QID or lovasta tin 20 mg BID or to conventional therapy: placebos, or colestipol if l ow-density lipoprotein cholesterol was elevated. End points included q uantitative arteriographic disease change and clinical events over a 2 .5-year interval. At baseline, symptomatic and asymptomatic patients h ad comparable risk profiles, but proximal stenosis severity averaged 3 6% for symptomatic and 23% for asymptomatic patients (P<.001). Among t he 91 symptomatic patients, those in the intensive group experienced d efinite (greater than or equal to 10%S) proximal lesion progression le ss frequently than conventional (24% of intensive versus 48% of conven tional) and definite regression more frequently (36% of intensive vers us 15% of conventional) (P=.009). Similarly, among the 29 asymptomatic patients, 19% of intensive versus 38% of conventional had progression and 31% of intensive versus 0% of conventional, regression (P=.04). I schemia on baseline exercise tolerance testing was associated with sig nificantly greater proximal disease progression among the asymptomatic patients. Clinical cardiovascular events (death, infarction, or revas cularization) occurred in 10 of 38 symptomatic patients originally ass igned to conventional therapy, compared with 5 of 76 symptomatic patie nts assigned to intensive (P<.01); no asymptomatic patient had an even t. Conclusions. Asymptomatic subjects with this high-risk profile have less coronary disease at baseline than comparable symptomatic patient s, and they have an excellent short-term clinical prognosis. However, asymptomatic subjects are indistinguishable from symptomatic patients in terms of their arterial disease progression with conventional thera py and their regression with intensive. These findings may justify an active treatment strategy in such subjects, particularly those with pr ovokable ischemia.