Effects of Intensive Lipid-Lowering Therapy on the Coronary Arteries of Asymptomatic Subjects With Elevated Apolipoprotein B

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Abstract

Background

Do the benefits of intensive lipid-lowering therapy seen in symptomatic patients extend to high-risk subjects who have never had symptoms?

Methods and Resuls

Of 120 men completing the FATS trial, 91 were symptomatic and 29 asymptomatic. All had apolipoprotein B 2125 mg/dL, a positive family history, and coronary atherosclerosis. All were counseled in diet and randomized to intensive therapy: colestipol 10 g TID plus either niacin 1 g QID or lovastatin 20 mg BID or to conventional therapy: placebos, or colestipol if low-density lipoprotein cholesterol was elevated. End points included quantitative arteriographic disease change and clinical events over a 2.5-year interval. At baseline, symptomatic and asymptomatic patients had comparable risk profiles, but proximal stenosis severity averaged 36% for symptomatic and 23% for asymptomatic patients (P<.001). Among the 91 symptomatic patients, those in the intensive group experienced definite (.101%S) proximal lesion progression less frequently than conventional (24% of intensive versus 48% of conventional) and definite regression more frequently (36% of intensive versus 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%1 of conventional, regression (P=.04). Ischemia on baseline exercise tolerance testing was associated with significantly greater proximal disease progression among the asymptomatic patients. Clinical cardiovascular events (death, infarction, or revascularization) occurred in 10 of 38 symptomatic patients originally assigned to conventional therapy, compared with 5 of 76 symptomatic patients assigned to intensive (P<.01); no asymptomatic patient had an event.

Concluions

Asymptomatic subjects with this high-risk profile have less coronary disease at baseline than comparable symptomatic patients, 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 therapy and their regression with intensive. These findings may justify an active treatment strategy in such subjects, particularly those with provokable ischemia.

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