Cardiovascular Mortality Risk Reduction with Intensive Lipid Therapy: 25-Year Follow-Up of the Familiar Atherosclerosis Treatment Study - Observational Study

Background: Burden of atherosclerotic risk factors and exposure are significantly predictive of the lifetime risk of cardiovascular (CVD) death.
Objective: Effect of long-term intensive lipid therapy on lifetime CVD mortality risk was investigated in a 25-year follow-up of the Familiar Atherosclerosis Treatment Study – Observational Study (FATS-OS).
Methods: Of 175 CAD subjects with mean LDL-C of 191 mg/dl and mean age of 50 years, who completed the randomized and placebo-controlled FATS, 100 choose receiving lipid management by their physicians (UC) and 75 elected to receive an intensive lipid therapy (IT) with lovastatin (40mg/day), niacin (2.5g/day) and colestipol (20g/day) from 1989 to 2004, followed by double therapy with simvastatin (40-80mg/day) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40-80 mg/day plus niacin during 2007-2012. Death from CVD and any cause were compared between UC and IT using Cox proportional hazards model.
Results: Mean LDL-C levels were 167 mg/dl from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119 mg/dl, 97, and 83 in the 3 time periods. Compared to UC, IT significantly reduced total mortality (11.1 vs. 26.3 per 1,000 PY, HR=0.45, 95% CI: 0.26-0.77, p=0.003) and CVD mortality (10.6 vs. 27.7 per 1,000 PY, HR=0.34, 95% CI: 0.15-0.80, p=0.009). Compared to lifetime risk of CVD mortality data from the epidemiologic studies, the IT group gained additional 13 years of survival.
Conclusions: A long-term intensive lipid therapy significantly reduced cardiovascular and total mortality over 25 years among subjects at high risk for cardiovascular mortality in FATS-OS. These results indicate the importance of lifetime cardiovascular risk management by early and long-term interventions.