Journal of Vascular Surgery
Volume 45, Issue 4 , Pages 645-654.e1 , April 2007

Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions

Presented at the Sixtieth Annual Meeting of the Society for Vascular Surgery, Philadelphia, Pa, June 1-4, 2006.

  • Heart Protection Study Collaborative Group

      Affiliations

    • Writing and other Committees are listed in the Appendix, and collaborators and participating hospitals are listed in reference 17.
    • (e-mail: hps@ctsu.ox.ac.uk).
    • Corresponding Author InformationCorrespondence to: Heart Protection Study, Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Building, University of Oxford, Old Road Campus, Roosevelt Dr, Oxford OX3 7LF, UK.

Received 30 May 2006 ,Accepted 18 December 2006.

References 

  1. Criqui MH, Fronek A, Barrett-Connor E, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985;71:510–515
  2. Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, Grobbee DE. Peripheral arterial disease in the elderly: The Rotterdam Study. Arterioscler Thromb Vasc Biol. 1998;18:185–192
  3. Fowkes FG, Housley E, Cawood EH, Macintyre CC, Ruckley CV, Prescott RJ. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol. 1991;20:384–392
  4. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381–386
  5. Jacobs D, Blackburn H, Higgins M, Reed D, Iso H, McMillan G, et al. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation. 1992;86:1046–1060
  6. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434–444
  7. Chen J, Campbell TC, Li J, Peto R. Diet, lifestyle and mortality in China. Oxford: Oxford University Press; 1990;
  8. Szatrowski TP, Peterson AV, Shimizu Y, Prentice RL, Mason MW, Fukunaga Y, et al. Serum cholesterol, other risk factors, and cardiovascular disease in a Japanese cohort. J Chronic Dis. 1984;37:569–584
  9. Fowkes FG, Housley E, Riemersma RA, Macintyre CC, Cawood EH, Prescott RJ, et al. Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Am J Epidemiol. 1992;135:331–340
  10. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389
  11. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. West of Scotland Coronary Prevention Study Group Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–1307
  12. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. Cholesterol and Recurrent Events Trial investigators The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–1009
  13. The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med. 1997;336:153–162
  14. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–1357
  15. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study). JAMA. 1998;279:1615–1622
  16. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience. Eur Heart J. 1999;20:725–741
  17. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22
  18. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005–2016
  19. Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004;363:757–767
  20. Rehring TF, Sandhoff BG, Stolcpart RS, Merenich JA, Hollis HW. Atherosclerotic risk factor control in patients with peripheral arterial disease. J Vasc Surg. 2005;41:816–822
  21. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient (II. analysis and examples). Br J Cancer. 1977;35:1–39
  22. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23–33
  23. White SJ, Freedman LS. Allocation of patients to treatment groups in a controlled clinical study. Br J Cancer. 1978;37:849–857
  24. Leng GC, Price JF, Jepson RG. Lipid-lowering for lower limb atherosclerosis. Cochrane Database Syst Rev. 2000;CD000123
  25. Meade T, Zuhrie R, Cook C, Cooper J. Bezafibrate in men with lower extremity arterial disease: randomised controlled trial. BMJ. 2002;325:1139–1144
  26. Heart Protection Study Collaborative Group. Cost-effectiveness of simvastatin in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20,536 individuals. Lancet. 2005;365:1779–1785
  27. Dormandy JA, Rutherford RB TASC Working Group TransAtlantic Inter-Society Concensus (TASC). Management of peripheral arterial disease (PAD). J Vasc Surg. 2000;31:S1–S296
  28. Pedersen TR, Kjekshus J, Pyorala K, Olsson AG, Cook TJ, Musliner TA, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian simvastatin survival study (4S). Am J Cardiol. 1998;81:333–335
  29. Aronow WS, Nayak D, Woodworth S, Ahn C. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Am J Cardiol. 2003;92:711–712
  30. Mohler ER, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108:1481–1486
  31. McDermott MM, Guralnik JM, Greenland P, Pearce WH, Criqui MH, Liu K, et al. Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation. 2003;107:757–761
  32. Mondillo S, Ballo P, Barbati R, Guerrini F, Ammaturo T, Agricola E, et al. Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med. 2003;114:359–364

 The study was funded by the UK Medical Research Council (MRC), the British Heart Foundation (BHF), Merck & Co (manufacturers of simvastatin), and Roche Vitamins Ltd (manufacturers of the vitamins).

 Competition of interest: The Clinical Trial Service Unit has a staff policy of not accepting honoraria or other payments from the pharmaceutical industry, except for the reimbursement of costs to participate in scientific meetings. Members of the writing committee have, therefore, only had such costs reimbursed.CME article

PII: S0741-5214(07)00003-1

doi: 10.1016/j.jvs.2006.12.054

Journal of Vascular Surgery
Volume 45, Issue 4 , Pages 645-654.e1 , April 2007