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    Mortality reduction in patients treated with long-term intensive lipid therapy: 25-year follow-up of the Familial Atherosclerosis Treatment Study—Observational Study

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    BACKGROUND: Cardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia. OBJECTIVES: The clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial 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, non-CVD and any cause were compared between UC and IT using Cox proportional hazards model. RESULTS: UC and IT groups were similar in risk factors with the exception that IT had more sever CAD. 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). The non-CVD mortality was also reduced, but was not of statistical significance (6.8 vs. 12.7 per 1,000 PY, HR=0.55, 95% CI: 0.27–1.14, p=0.11). CONCLUSIONS: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in FATS-OS. These results support the importance of lifetime risk management to improve long-term outcome
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