Abstract
Clinical trials that evaluate more aggressive cholesterol reduction in a broader range of patients at high risk for coronary heart disease (CHD) are needed to fill gaps in our understanding of the impact of lipid‐lowering therapy on risks for clinical events and mortality. This paper briefly reviews results from recent landmark studies that have evaluated the benefits of aggressive lipid‐lowering therapy in patients with, or at risk for, CHD. The Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study demonstrated that aggressive treatment with atorvastatin was significantly more effective than less aggressive therapy with pravastatin in slowing the progression of atherosclerosis in patients with symptomatic CHD. Results from two large‐scale clinical end‐point trials, the Heart Protection Study (HPS) and the Anglo‐Scandinavian Cardiac Outcomes Trial‐Lipid Lowering Arm (ASCOT‐LLA), have shown that aggressive lipid‐lowering treatment in patients with relatively low baseline levels of low‐density lipoprotein cholesterol (LDL‐C) significantly reduces CHD risk. Taken together, the results of these landmark trials not only support aggressive lipid lowering in patients at risk for CHD, but also suggest that greater LDL‐C reductions may improve outcomes across a wide range of patients.
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References
- 1. Multiple Risk Factor Intervention Trial Research Group : Relationship between baseline risk factors and coronary heart disease and total mortality in the Multiple Risk Factor Intervention Trial. Prev Med 1986; 15: 254–273 [DOI] [PubMed] [Google Scholar]
- 2. Menotti A, Keys A, Blackburn H, Kromhout D, Karvonen M, Nissinen A, Pekkanen J, Punsar S, Fidanza F, Giampaoli S, Seccareccia F, Buzina R, Mohacek I, Nedeljkovic S, Aravanis C, Dontas A, Toshima H, Lanti M: Comparison of multivariate predictive power of major risk factors for coronary heart diseases in different countries: Results from eight nations of the Seven Countries Study, 25‐year follow‐up. J Cardiovasc Risk 1996; 3: 69–75 [PubMed] [Google Scholar]
- 3. Chen Z, Peto R, Collins R, MacMahon S, Lu J, Li W: Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. Br Med J 1991; 303: 276–282 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Neaton JD, Wentworth D, for the Multiple Risk Factor Intervention Trial Research Group : Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Arch Intern Med 1992; 152: 56–64 [PubMed] [Google Scholar]
- 5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary. NIH Publication No. 01‐3670. May 2001. [DOI] [PubMed]
- 6. Fedder DO, Koro CE, L'Italien GJ: New National Cholesterol Education Program III guidelines for primary prevention lipid‐lowering drug therapy: Projected impact on the size, sex, and age distribution of the treatment‐eligible population. Circulation 2002; 105: 152–156 [DOI] [PubMed] [Google Scholar]
- 7. Scandinavian Simvastatin Survival Study Investigators : Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–1389 [PubMed] [Google Scholar]
- 8. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301–1307 [DOI] [PubMed] [Google Scholar]
- 9. Sacks FM, Pfeffer MA, Moyé LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001–1009 [DOI] [PubMed] [Google Scholar]
- 10. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr: 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. J Am Med Assoc 1998; 279: 1615–1622 [DOI] [PubMed] [Google Scholar]
- 11. 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 [DOI] [PubMed] [Google Scholar]
- 12. Vrecer M, Turk S, Drinovec J, Mrhar A: Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta‐analysis of randomized trials. Int J Clin Pharmacol Ther 2003; 41: 567–577 [DOI] [PubMed] [Google Scholar]
- 13. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN, and the REVERSAL Investigators : Effect of intensive compared with moderate lipid‐lowering therapy on progression of coronary atherosclerosis: A randomized controlled trial. J Am Med Assoc 2004; 291: 1071–1080 [DOI] [PubMed] [Google Scholar]
- 14. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J, and the ASCOT Investigators : Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower‐than‐average cholesterol concentrations, in the Anglo‐Scandinavian Cardiac Outcomes Trial‐Lipid Lowering Arm (ASCOT‐LLA): A multi‐centre randomised controlled trial. Lancet 2003; 361: 1149–1158 [DOI] [PubMed] [Google Scholar]
- 15. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, and the National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee : The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. J Am Med Assoc 2003; 289: 2560–2572 [Google Scholar]
- 16. 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 12114036 [Google Scholar]
- 17. Collins R, Armitage J, Parish S, Sleigh P, Peto R: Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol‐lowering with simvastatin in 5,963 people with diabetes: A randomised placebo‐controlled trial. Lancet 2003; 361: 2005–2016 [DOI] [PubMed] [Google Scholar]
- 18. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group : Major outcomes in high‐risk hypertensive patients randomized to angiotensin‐converting enzyme inhibitor or calcium channel blocker vs. diuretic: The Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Am Med Assoc 2002; 288: 2981–2997 [DOI] [PubMed] [Google Scholar]
- 19. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group : Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs. usual care: The Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT‐LLT). J Am Med Assoc 2002; 288: 2998–3007 [DOI] [PubMed] [Google Scholar]