Mortality Reduction in Patients Treated with Long-term Intensive Lipid Therapy: 25-year Follow-up of the Familial Atherosclerosis Treatment Study-Observational Study

Overview

Journal J Clin Lipidol

Publisher Elsevier

Specialties Biochemistry
Endocrinology

Date 2016 Sep 29

PMID 27678425

Citations 2

Authors

Xue-Qiao Zhao

Binh An P Phan

Joseph Davis

Daniel Isquith

Alice A Dowdy

Suzanne Boltz

Moni Neradilek

Erik A Monick

Andrew Brockenbrough

Ellen E Hus-Frechette

John J Albers

B Greg Brown

Affiliations

Soon will be listed here.

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.

Citing Articles

Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events.

Zhan S, Tang M, Liu F, Xia P, Shu M, Wu X Cochrane Database Syst Rev. 2018; 11:CD012502.

PMID: 30480766 PMC: 6516816. DOI: 10.1002/14651858.CD012502.pub2.

High-density Lipoprotein and Low-density Lipoprotein Therapeutic Approaches in Acute Coronary Syndromes.

Androulakis E, Zacharia E, Papageorgiou N, Lioudaki E, Bertsias D, Charakida M Curr Cardiol Rev. 2017; 13(3):168-182.

PMID: 28190386 PMC: 5633711. DOI: 10.2174/1573403X13666170209145622.

References

Shepherd J, Cobbe S, Ford I, Isles C, LORIMER A, Macfarlane P . Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995; 333(20):1301-7. DOI: 10.1056/NEJM199511163332001. View

Fulcher J, OConnell R, Voysey M, Emberson J, Blackwell L, Mihaylova B . 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):1397-405. DOI: 10.1016/S0140-6736(14)61368-4. View

Stitziel N, Won H, Morrison A, Peloso G, Do R, Lange L . Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014; 371(22):2072-82. PMC: 4335708. DOI: 10.1056/NEJMoa1405386. View

Jacobson T, Ito M, Maki K, Orringer C, Bays H, Jones P . National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol. 2015; 9(2):129-69. DOI: 10.1016/j.jacl.2015.02.003. View

Criqui M, Langer R, Fronek A, Feigelson H, Klauber M, McCann T . Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992; 326(6):381-6. DOI: 10.1056/NEJM199202063260605. View

Versmissen J, Oosterveer D, Yazdanpanah M, Defesche J, Basart D, Liem A . Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008; 337:a2423. PMC: 2583391. DOI: 10.1136/bmj.a2423. View

Nordestgaard B, Chapman M, Humphries S, Ginsberg H, Masana L, Descamps O . Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013; 34(45):3478-90a. PMC: 3844152. DOI: 10.1093/eurheartj/eht273. View

Navar-Boggan A, Peterson E, DAgostino Sr R, Neely B, Sniderman A, Pencina M . Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation. 2015; 131(5):451-8. PMC: 4370230. DOI: 10.1161/CIRCULATIONAHA.114.012477. View

Brown G, Albers J, Fisher L, Schaefer S, Lin J, Kaplan C . 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):1289-98. DOI: 10.1056/NEJM199011083231901. View

10.

Heart Protection Study Collaborative Group . Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet. 2011; 378(9808):2013-2020. PMC: 3242163. DOI: 10.1016/S0140-6736(11)61125-2. View

11.

Stone N, Robinson J, Lichtenstein A, Merz C, Blum C, Eckel R . 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 63(25 Pt B):2889-934. DOI: 10.1016/j.jacc.2013.11.002. View

12.

Ference B, Majeed F, Penumetcha R, Flack J, Brook R . Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study. J Am Coll Cardiol. 2015; 65(15):1552-61. PMC: 6101243. DOI: 10.1016/j.jacc.2015.02.020. View

13.

Malloy M, Kane J, Kunitake S, Tun P . Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia. Ann Intern Med. 1987; 107(5):616-23. DOI: 10.7326/0003-4819-107-5-616. View

14.

Cohen J, Boerwinkle E, Mosley Jr T, Hobbs H . Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006; 354(12):1264-72. DOI: 10.1056/NEJMoa054013. View

15.

Lloyd-Jones D, Leip E, Larson M, DAgostino R, Beiser A, Wilson P . Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006; 113(6):791-8. DOI: 10.1161/CIRCULATIONAHA.105.548206. View

16.

Berry J, Dyer A, Cai X, Garside D, Ning H, Thomas A . Lifetime risks of cardiovascular disease. N Engl J Med. 2012; 366(4):321-9. PMC: 3336876. DOI: 10.1056/NEJMoa1012848. View

17.

Ross R . Atherosclerosis--an inflammatory disease. N Engl J Med. 1999; 340(2):115-26. DOI: 10.1056/NEJM199901143400207. View

18.

Roe M, Messenger J, Weintraub W, Cannon C, Fonarow G, Dai D . Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol. 2010; 56(4):254-63. DOI: 10.1016/j.jacc.2010.05.008. View

19.

Cannon C, Blazing M, Giugliano R, McCagg A, White J, Theroux P . Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015; 372(25):2387-97. DOI: 10.1056/NEJMoa1410489. View

20.

Ford I, Murray H, Packard C, Shepherd J, Macfarlane P, Cobbe S . Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007; 357(15):1477-86. DOI: 10.1056/NEJMoa065994. View