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

Abstract

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.

Methods: Of 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths 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 severe coronary artery disease. 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, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11).

Conclusions: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome.

Keywords: Cardiovascular disease; Lifetime risk; Lipid-lowering therapy; Mortality.

Figure 1

Study design of the 25-year observational study (OS) following the Familiar Atherosclerosis Treatment Study (FATS). After original FATS, 75 subjects choose to continued intensive lipid therapy (IT) and 100 others decided to return to the usual care (UC) of their physicians. The intensity of lipid treatment in the IT group was achieved based on the targeted LDL-C levels recommended by the National Cholesterol Education Program guidelines.

Figure 2

Kaplan-Meier estimated event-free survival over 25 years in FATS-OS by treatment. Panel A: survival from any death. HR (IT/UC) = 0.45 (95% CI 0.26–0.77), P=0.003 using log-rank test. Panel B: survival from cardiovascular death. HR (IT/UC) = 0.34 (95% CI 0.15–0.80), P=0.009. Panel C: survival from non-cardiovascular death. HR (IT/UC) = 0.55 (95% CI 0.27–1.14), P=0.11.