Table 2, Cholesterol Studies Conducted from 1955 through 2011

Year Study Author Type Intervention No Pt Population End Point Finding
1955 Framingham Study; 30-year examination Anderson Observation None 4,374 Primary Death,MI Association of Chol and death from CAD; F/U was 18 years w/ only 3% dropout rate; Mortality for men (p<0.01) and women (p<0.05); 5% inc in death with each 10 mg% inc in Chol; MI death assoc is higher with 9% inc in death for each 10% inc Chol (p<0.01)
1984 Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) Group RCT Cholestyramine 3,806 Primary Death,MI Reduction in death & MI by 1.6%
1991 Multiple Risk Factor Intervention Trial Research (MRFIT) Group Observation None 361,662 Primary Death fr MI BP, Chol, Smoking: Chol > 180 mg% assoc w/ Death
1995 Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia Shepherd RCT Pravastatin 6,595 Primary MI Reduction in MI by 1.1% (p=0.001)
1996 Cholesterol and Recurrent Events (CARE) Sacks RCT Pravastatin 4,159 CAD Death,MI Death from MI reduced by 3% (p<.003); same for CVA; LDL below 125 did not confer benefit
1997 National Cholesterol Education Program (NCEP) Cleeman Review None       NCEP makes recommendations for Chol screening & treatment; Borderline high-risk LDL > 130; High-risk LDL > 160
1997 Effects of Serum Lipoproteins and Smoking on Atherosclerosis in Young Men and Women McGill, HC Observation Autopsy 1,443 Sudden death Death Fatty acid streaks correlate with high LDL and low HDL levels; Smoking correlates w/ size of fatty streaks and raised lesions
1998 AFCAPS/TexCAPS Downs JR RCT Lovastatin 6,605 Primary MI Reduction in MI by 1.0% (p=0.001)
2000 Follow-Up Study of Patients Randomized in the Scandinavian Simvastatin Survival Study (4S) of Cholesterol Lowering Pedersen, TR RCT Simvastatin 4,006 Death Long-term effects; death in placebo (15.9%) vs Simvastatin (11.5%) has a p=0.00002; cancer deaths were NS
2001 MIRACL Schwartz RCT Atorvastatin 3,086 ACS Death,MI,CVA Atorvastatin 80 mg/d vs placebo; 3.6% reduction in recurrent MI within 16 weeks of 1st cardiac event (p = 0.048); CVA risk was also reduced by 0.8% (p < 0.05)
2002 Heart Protection Study Collaborative RCT Simvastatin 20,536 Primary Death,MI,CVA Reduction in Death by 1.8% (p=00003); and MI death by 18% (p=.0005); and MI by 3.1% (p=0.0001); and CVA by 1.4% (p=0.0001)
2002 Adult Treatment Panel II Versus Adult Treatment Panel III: What Has Changed and Why? Pasternak, R Review None       Guidelines (old)
2004 Aggressively in Lipid-Lowering Disease Management Clinics (ALLIANCE) Koren RCT Atorvastatin 2,442 Primary MI LDL < 80; reduced MI by 3.4% (p=0.0002)
2004 Collaborative Atorvastatin Diabetes Study (CARDS) Colhoun, HM RCT Atorvastatin 2,838 DM MI,CVA Reduction by 1.6% (p=0.001)
2004 PROVE-IT: Atorvastatin vs Pravastatin Cannon, CP RCT Atorvastatin vs Pravastatin 4,162 CAD Death,MI,CVA, other vasc events Atorvastatin 80 mg/d vs Pravastatin 40 mg/d; Atorvastatin over Pravastatin had 3.9% reduction in cardiovascular events (p < 0.001); Suggests an LDL target of <70 mg%
2005 Treating to New Targets (TNT) LaRosa RCT Atorvastatin 10,001 CAD Death,MI Pt w/ CAD; Mean LDL=77, Reduction in MI by 2.2% (p<0.001)
2005 IDEAL: Atorvastatin vs Simvastatin Pedersen, TR RCT Atorvastatin vs Simvastatin 8,888 CAD MI Atorvastatin 80 mg/d vs Simvastatin 20 mg/d; Only nonfatal MI was reduced by 2.2% (p < 0.02); Transaminase levels rose in only 1% of pt on Atorvastatin & 0.1% on Simvastatin; mortality difference did not reach statistical significance; Safety of high-dose Atorvastatin is established
2008 IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) Cannon, CP RCT Ezetimibe & Simvastatin 18,000 CAD   Pending study
2008 Evidence for Dietary Prevention VanHorn, L Review Diet       Polyunsaturated FA lower LDL; diets low in Sat FA had reduced risk CAD (p<0.001); 118 pt in 3 RCT included; Plant Sterols & Stanol reduce CAD by OR=0.78 (p<0.05); Soluble Fiber: beta-glucans reduce LDL by 7.7%, w/ Oat bran Fiber by 1.96 mg%; Fiber interfers w/ Chol absorption; EPA & DHA (fish) show reduced CAD (p=0.03); however, many conflicting studies; ALA (nuts) show lower CAD risk, more convincing (p<0.01); Folate, Vit B-6 & B-12 reduced restenosis rate (p<0.001); Physicians Health Study shows <6 ETOH drinks/wk reduces CAD (p=0.05)
2008 Lifestyle Approaches and Dietary Strategies to Lower LDL-Cholesterol and Triglycerides and Raise HDL-Cholesterol Katcher, HI Review Diet       Seven Countries Studies correlate SFA w/ elevation of LDL; IOM, AHA recommendations; Table of food substitutions; Diagram showing TFA > SFA in raising LDL; image of cholesterol; Omega-3 FA; other dietary measures incl ETOH; Wt loss w/ low CHO vs low Fat; Mediterranean diet
2009 ASTEROID Study Wiviott, SD Prospective Open labeled Rosuvastatin 471 CAD   For pt LDL < 70 mg% no major SE; study limited due to low power; US of coronary arteries failed to show regression
2009 JUPITER Glynn, RJ RCT Rosuvastatin 8,901 Primary CRP LDL < 30; CRP > 2; CRP drops with Rosuvastatin therapy
2010 Combination Statin & Ezetimibe Toth Review Ezetimibe & Statins     Serogates Lowers LDL, CRP
2010 Intake of Fish & n-3 FA Baik, I Cohort Diet: fish 3,504 Primary Metabolic Syn Fish intake assoc'd with reduced metabolic syn only in men OR 0.53
2010 JUPITER Ridker, PM RCT Rosuvastatin 17,802 Primary MI Rosuvastatin reduced MI by 44% (p<0.0001); funded by AstraZeneca
2011 Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Group RCT Pravastatin 9,014 CAD Death,MI Death from MI reduced by 1.9% (p<.001)