FATS- Familial Atherosclerosis Treatment Study

Familial Atherosclerosis Treatment Study (FATS) Randomized, double-blind, placebo-controlled (or colestipol-controlled) study. 146 men with apolipoprotein B  125 mg/dL (3.23 mmol/L), documented coronary artery disease and family history of vascular disease. Randomized to diet plus: - Lovastatin (40 mg/d) + colestipol. - Niacin (4 g/d) + colestipol. - Conventional therapy (+ placebo or colestipol). Endpoints: - Change in severity of stenosis (based on an average of the most severe stenoses in 9 proximal coronary segments) at the end of the study, as assessed by coronary arteriography . - Clinical events (death, MI or revascularization for worsening symptoms. FATS: Familial Atherosclerosis Treatment Study The aim of this study was to compare two intensive strategies for modification of lipid levels with a more conventional approach in men at particularly high risk of cardiovascular disease as a result of established coronary atherosclerosis. Reference Brown G, Albers JJ, Fisher LD et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289-98 Brown G et al. N Engl J Med 1990; 323:1289-98.

FATS - Effect on lipids at 2.5 years FATS: Familial Atherosclerosis Treatment Study Both intensive treatment regimens were more effective reducing levels of LDL cholesterol and triglycerides (in fact, there was an increase in triglycerides in patients receiving conventional therapy), as well as raising HDL cholesterol. Notably, the combination niacin treatment was most effective in raising HDL cholesterol by 43% relative to baseline. Reference Brown G, Albers JJ, Fisher LD et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289-98 Brown G et al. N Engl J Med 1990; 323:1289-98.

FATS - Effect on primary endpoint FATS: Familial Atherosclerosis Treatment Study The main study endpoint was the change in severity of stenosis (based on an average of the most severe stenoses in 9 proximal coronary segments) at the end of the study, as assessed by coronary arteriography. Lipid changes observed in the group treated with niacin combination therapy were associated with a higher prevalence of net regression of atherosclerotic lesions (in at least 1 of 9 proximal lesions) compared with conventional treatment (39% vs. 11% of patients, p<0.005). Reference Brown G, Albers JJ, Fisher LD et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289-98 Brown G et al. N Engl J Med 1990; 323:1289-98.

FATS – Effect on clinical events FATS: Familial Atherosclerosis Treatment Study Although the study was not powered to evaluate the effect of the combination niacin treatment on clinical outcomes, death, MI or revascularisation for worsening symptoms occurred in a lower proportion of patients treated with this combination (2/48, 4%) compared with those treated with conventional therapy (10/52, 19%). Reference Brown G, Albers JJ, Fisher LD et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289-98 Brown G et al. N Engl J Med 1990; 323:1289-98.

FATS – 10 year follow-up FATS: Familial Atherosclerosis Treatment Study, 10-year follow-up A 10-year follow-up of FATS compared the effect of treatment with an aggressive triple therapy (statin plus niacin plus a bile acid sequestrant) with usual care. Cardiovascular events were total mortality were substantially reduced with the triple therapy regimen (p<0.05). Although this was a small and not formally randomised study, these results suggest a benefit with aggressive lipid-modifying therapy in patients with low HDL cholesterol. Reference Brown BG, Brockenbrough A, Zhao X-Q et al. Very intensive lipid therapy with lovastatin, niacin, and colestipol for prevention of death and myocardial infarction: a 10-year Familial Atherosclerosis Treatment Study (FATS) follow-up. Circulation 1998;98: I-635. Brown G et al. N Engl J Med 1990; 323:1289-98.