Physicians' Academy for Cardiovascular Education

Very long-term intensive lipid-lowering therapy pays off with mortality benefit in CAD

Zhao XQ et al., J Clin Lipidol 2016

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


Zhao XQ, Phan BA, Davis J, et al.
J Clin Lipidol 2016;10(5):1091-7
 

Background

CV risk is dependent on the number and the length of exposure to CV risk factors [1]. Randomised clinical trials demonstrating a CVD event reduction associated with LDL-C lowering lasted up to 7 years [2,3].
In this study, the long-term clinical benefit of intensive lipid therapy was assessed in 175 men with hypercholesterolaemia during a 25-year observational study: the Familial Atherosclerosis Treatment Study-Observational Study (FATS) trial [4]. The FATS observational trial originated in the FATS randomised trial. Patients who finished the randomised phase were asked whether they wanted to continue indefinitely on the triple-therapy regime that was evaluated in a pilot study as part of the FATS randomised study.
75 out of 86 wanted to continue triple therapy (intensive treatment (IT): lovastatin 40 mg/d, niacin 2.5 g/d and colestipol 20 g/d from 1989 through 2004, followed by double therapy with simvastatin (40-80 mg/d) plus niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin (40-80 mg/d) plus niacin from 2007 till 2012). The remaining 11 plus 89 subjects who finished FATS before 1988 returned to lipid management by their physician (usual care: UC). Risk factors were similar between groups, except that the IT group had more severe coronary artery disease.
 

Main results

  • In patients receiving UC, the mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 mg/dL from 2005 to 2006, and 96 mg/dL from 2007 to 2012 in surviving subjects.
    Subjects in the IT group had mean LDL- C levels of 119 mg/dL from 1988 to 2004, 97 mg/dL from 2005 to 2006, and 83 mg/dL from 2007 to 2012.
  • During the 25 years of follow-up, there were 70 deaths in total, 52 in the US group and 18 in the IT group. Compared with the UC group, the IT group had significantly lower total mortality (11.1 vs 26.3 per 1000 person years [PY], HR: 0.45; 95% CI: 0.26–0.77; P = 0.003), significantly lower CV mortality (10.6 vs 27.7 per 1000 PY, HR: 0.34; 95% CI: 0.15–0.80; P = 0.009), lower non-CV mortality (6.8 vs 12.7 per 1000 PY, HR: 0.55; 95% CI: 0.27-1.14; P = 0.11).
  • In the multivariate analysis, IT, history of MI, and history of ischemic leg pain were identified as independent factors associated with total mortality. IT independently reduced total mortality risk by 53% (HR: 0.47; 95% CI: 0.26–0.85; P = 0.01), risk of CV death by 70% (HR: 0.30; 95% CI: 0.12–0.74, P = 0.01), and risk of non-CV death by 29% (HR: 0.71; 95% CI: 0.32–1.55; P = 0.4).
 

Conclusion

Intensive lipid-lowering therapy for 25 years was associated with significant reductions in CV and total mortality in men with hypercholesterolaemia and established coronary artery disease.
 
Find this article online at J Clin Lipidol
 

References

1. Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006;113:791–798.
2. Cholesterol Treatment Trialists’ (CTT) Collaboration, Fulcher J, O’Connell R, Voysey M, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015; 385(9976):1397–1405.
3. Cannon CP, Blazing MA, Giugliano RP, et al, IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.
4. Brown BG, 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(19):1289–1298.