Table 1:
Description of studies included in the systematic review
| Study, year, location | Population | Sample size in statin/no-statin groups (mean follow-up, yr) | Statin and starting dose, mg/d | Cardiovascular history (%) | 10-yr risk of NFMI or CV death in controls, % | D’Agostino CVD risk,* % | DM HTN, % | Mean TC, LDL-C, HDL-C and TG levels, mmol/L | Mean age, yr (% male) |
|---|---|---|---|---|---|---|---|---|---|
| ASTRONOMER47 2010 Canada |
Men and women 18–82 yr; asymptomatic mild to moderate aortic stenosis (maximum aortic value velocity 2.5–4 m/s); no CAD, CVD, PVD or diabetes | 134/135 (3.5) | Rosuvastatin 40 | NA | 16 | 15 | 0 NR |
5.3 3.2 1.6 1.3 |
58 (62) |
| ESPLANADE49 2010 Italy |
>16 yr; BP >140/90 mm Hg or concomitant antihypertensive therapy; 24-hour proteinuria persistently >1 g (later changed to > 0.5 g) after 2-mo washout from previous treatment with RAS inhibitors or statins; no evidence of urinary tract infections or heart failure | 87/93 (0.5) | Fluvastatin 40–80 | NR | 0 | 18 | 17 NR |
5.6 3.6 1.2 1.4 |
51 (76) |
| LEADe46 2010 10 countries |
Men and women 50–90 yr; diagnosis of probable Alzheimer disease; taking donepezil 10 mg for ≥ 3 mo; LDL-C 2.5–3.5 mmol/L unless DM present (LDL-C < 10%); 2.5–3.5 mmol/L, blood sugar stable and HbA1C no clinically significant or unstable medical condition | 314/325 (1.4) | Atorvastatin 80 | NA | 13 | 28 | NR NR |
5.8 3.7 1.6 1.5 |
74 (48) |
| LORD48 2010 Australia |
18–85 yr with chronic kidney disease (SCr > 120 μmol/L); all levels of proteinuria and serum cholesterol; no previous lipid-lowering therapy | 58/65 (2.5) | Atorvastatin 10 | NR | 12 | 26 | 8 NR |
5.6 3.4 1.2 2.3 |
60 (65) |
| JUPITER4 2008 26 countries |
Men ≥ 50 yr and women ≥ 60 yr; no history of CVD; LDL-C < 3.4 mmol/L, TG < 5.6 mmol/L, high-sensitivity CRP ≥ 2.0 mg/dL; no previous/current use of lipid- lowering therapy | 8901/8901 (median 1.9) | Rosuvastatin 20 | NA | 6 | 22 | 0 NR |
4.8 2.8 1.3 1.3 |
66 (62) |
| Yun et al.50 2008 Korea |
Chest pain at rest; no significant CAD; no acute MI within 6 mo; no previous coronary intervention | 37/37 (0.5) | Rosuvastatin 10 | NR | 0 | 18 | 9 51 |
5.0 3.0 1.2 1.7 |
57 (48) |
| Bone et al.23 2007 USA |
Postmenopausal women 40–75 yr, LDL-C ≥ 3.4 < 4.9 mmol/L; no history of diabetes or CHD | 485/119 (1) | Atorvastatin 10, 20, 40, 80 | NA | 0 | 15 | 0 NR |
6.3 4.0 1.5 1.6 |
59 (0) |
| METEOR34 2007 USA |
Men 40–70 yr and women 55–70 yr; LDL-C < 4.1 mmol/L, HDL-C ≤ 1.6 mmol/L, TG < 5.7 mmol/L; 10-yr risk of CAD events < 10%; no evidence of CAD or other peripheral atherosclerotic disease; no previous revascularization; no diabetes | 702/282 (2) | Rosuvastatin 40 | NA | 0 | 14 | 0 28 |
5.9 4.0 1.3 1.4 |
57 (60) |
| MEGA24 2006 Japan |
Men and postmenopausal women 40–70 yr; TC 5.69– 6.98 mmol/L; no history of CHD or stroke | 3866/3966 (5.3) | Pravastatin 10–20 | NA | 2 | 18 | 21 42 |
6.3 4.1 1.5 1.4 |
58 (31) |
| Dernellis et al.35 2005 Greece |
Adults with CRP 0.8–1.3 mg/dL; at least one episode of PAF on ambulatory monitoring | 40/40 (0.5) | Atorvastatin 20–40 | NR | 0 | 20 | 20 65 |
5.8 4.0 1.2 NR |
52 (65) |
| Di Lullo et al.25 2005 Italy |
Men and women 18–80 yr; mild/moderate CRF for ≥ 5 yr; CRP 3–14 mg/dL, TC 6.5–9.1 mmol/L, HDL-C 1.3–1.8 mmol/L, LDL-C 2.6–4.9 mmol/L, TG 1.8–5.1 mmol/L; no diagnosis of severe heart failure or familial hypercholesterolemia; no cardiac illness | 80/50 (0.7) | Fluvastatin XL 80 | NA | 0 | 32 | 35 65 |
7.6 4.0 1.7 2.6 |
59 (54) |
| Holmberg et al.26 2005 Sweden |
≥ 18 yr; GFR < 30 mL/min per body surface area of 1.73 m2 | 70/73 (1.8) | Atorvastatin 10 | NR | 0 | 40 | 31 NR |
5.8 3.5 1.1 2.4 |
69 (69) |
| HYRIM28 2005 Norway |
Drug-treated hypertensive men 40–75 yr; TC 4.5–8 mmol/L, TG < 4.5 mmol/L; no symptomatic CVD, CHF, type I DM or history of coronary intervention | 283/285 (4) | Fluvastatin† 40 | NA | 8 | 26 | NR 100 |
5.9 3.9 1.3 1.8 |
57 (100) |
| UK-HARP-I27 2005 UK |
Men and women ≥ 18 yr; 1) pre-dialysis with PCr or SCr ≥ 1.7 mg/dL; under dialysis; or functioning renal transplant, and 2) no definite indication or contraindication for cholesterol-lowering therapy or ASA | 224/224 (1) | Simvastatin† 20 | Vascular disease‡ (9) | 9 | 22 | 12 NR |
5.2 3.2 1.0 2.1 |
53 (79) |
| Muldoon et al.29 2004 USA |
Hypercholesterolemic men and women 35–70 yr; LDL-C 4.1–5.7 mmol/L; no CAD, stroke, diabetes or current lipid-lowering medication | 206/102 (0.5) | Simvastatin 10, 40 | NA | 0 | 15 | 0 NR |
6.8 4.7 1.3 1.7 |
54 (48) |
| PHYLLIS30 2004 Italy |
Men and postmenopausal women 45–70 yr; untreated or uncontrolled HTN, hypercholesterolemia, asymptomatic carotid atherosclerosis; no previous CVA events; LDL-C 4.14–5.17 mmol/L, TG ≤ 3.39 mmol/L | 254/254 (2.6) | Pravastatin† 40 | NA | 5 | 21 | NR 100 |
6.8 4.7 1.4 1.6 |
58 (40) |
| PREVEND-IT31 2004 Netherlands |
28–75 yr; persistent microalbuminuria; BP < 160/100 mm Hg without use of antihypertensive medication; TC < 8 mmol/L (< 5 mmol/L if previous MI); no use of lipid-lowering medication | 433/431 (3.8) | Pravastatin† 40 | MI (1) CVA (1) PVD (1) | 11 | 14 | 3 NR |
5.8 4.1 1.0 1.4 |
51 (65) |
| Rejnmark et al.32 2004 Denmark |
Healthy, postmenopausal women < 76 yr; no previous statin use within 2 yr | 41/41 (1.5) | Simvastatin 40 | NA | 0 | 15 | NR NR |
6.5 4.0 1.9 1.2 |
64 (0) |
| ASCOT–LLA36 2003 Europe |
Men and women 40–79 yr; TC ≤ 6.5 mmol/L; not taking lipid-lowering therapy; ≥ 3 CVD risk factors; no previous MI or heart failure | 5168/5137 (median 3.3) | Atorvastatin 10 | Stroke/TIA (10) PVD (5) Other CVD (4) | 11 | 42 | 25 80 |
5.5 3.4 1.3 1.7 |
63 (81) |
| Bruckert et al.33 2003 France, Italy, Spain, Belgium, Israel |
Men and women 70–85 yr; primary hypercholesterolemia (TC ≥ 6.5 mmol/L, TG ≥ 4.6 mmol/L, LDL-C ≥ 4.1 mmol/L after dietary intevention); no symptomatic CHF, history of MI, angina or stroke | 607/622 (1) | Fluvastatin XL 80 | CHF (0.4) TIA (2) | 2 | 33 | 7 56 |
7.3 5.2 1.4 1.5 |
76 (25) |
| ALLHAT–LLT40 2002 Canada, USA, Puerto Rico, Virgin Islands |
Age ≥ 55 yr; stage I or II HTN; ≥ 1 additional CHD risk factor; fasting LDL-C 3.1–4.9 mmol/L (if no known CHD) or 2.6–3.3 mmol/L (if known CHD); fasting TG < 3.9 mmol/L | 5170/5185 (4.8) | Pravastatin 20–40 | CHD (14) | 18 | 36 | 35 100 |
5.8 3.8 1.2 1.7 |
66 (51) |
| KLIS37 2000 Japan |
Men 45–75 yr; primary hypercholesterolemia (TC ≥ 5.69 mmol/L) in at least two measurements; no history of MI or coronary bypass surgery | 2219/1634 (5) | Pravastatin 10–20 | NA | 3 | 33 | 23 43 |
6.4 4.3 1.3 1.9 |
58 (100) |
| Bak et al.44 1998 Netherlands |
Men 40–70 yr; TC 6.5–8 mmol/L, TG ≤ 4 mmol/L; no CVD; no prior use of lipid-lowering drugs | 106/109 (0.5) | Pravastatin† 20 | NA | 0 | 24 | NR NR |
7.3 5.2 1.1 2.1 |
55 (100) |
| AFCAPS/TexCAPS39 1998 USA |
Men 45–73 yr and postmenopausal women 55–73 yr; no history of MI, angina, claudication, CVA or TIA; TC 4.65–6.82 mmol/L, LDL-C 3.36–4.91 mmol/L, HDL-C ≤ 1.16 mmol/L for men and ≤ 1.22 for women, TG ≤ 4.53 mmol/L | 3304/3301 (5.2) | Lovastatin 20–40 | NA | 7 | 28 | 4 22 |
5.7 3.9 1.0 1.8 |
58 (85) |
| CAIUS42 1996 Italy |
Men and women 45–65 yr; three baseline determinations of LDL-C 3.88–6.47 mmol/L and TG < 2.82 mmol/L; no CAD; at least one carotid artery lesion detected by ultrasound imaging | 151/154 (3) | Pravastatin 40 | NA | 4 | 18 | 0 NR |
6.8 4.7 1.4 1.6 |
55 (53) |
| KAPS41 1995 Finland |
Men 44–65 yr; LDL-C > 4.25 mmol/L, TC < 8.0 mmol/L, BMI < 32 kg/m2, ALT/AST ≤ 1.5-fold the laboratory upper normal limit | 224/223 (3) | Pravastatin 40 | MI (8) | 13 | 29 | 2 33 |
6.7 4.9 1.2 1.7 |
57 (100) |
| WOSCOPS43 1995 Scotland |
Men 45–64 yr; hypercholesterolemia (LDL-C 4.5– 6 mmol/L); no history of MI or other serious illness | 3302/3293 (4.9) | Pravastatin 40 | Vascular disease** (16) | 17 | 31 | 1 16 |
7.0 5.0 1.1 1.8 |
55 (100) |
| ACAPS38 1994 USA |
Men and women 40–79 yr; early carotid atherosclerosis; moderately elevated LDL-C; no history of stroke, TIA, angina or MI | 460/459 (2.8) | Lovastatin† 20–40 | NA | 8 | 21 | 2 29 |
6.1 4.0 1.3 3.6 |
62 (52) |
| EXCEL45 1991 USA |
Men and women (postmenopausal or surgically sterile) 18–70 yr; fasting plasma TC 6.2–7.6 mmol/L, LDL-C ≥ 4.1 mmol/L; no unstable medical conditions, impaired hepatic or renal function | 6582/1663 (0.9) | Lovastatin 20, 40, 80 | CHD (29) | 13 | 21 | NR 40 |
6.7 4.7 1.2 1.8 |
56 (59) |
Note: ALT = alanine aminotransferase, ASA = acetylsalicylic acid, AST = aspartate aminotransferase, BMI = body mass index, BP = blood pressure, CAD = coronary artery disease, CHD = coronary heart disease, CHF = congestive heart failure, CRF = chronic renal failure, CRP = C-reactive protein, CV = cardiovascular, CVA = cerebrovascular accident, CVD = cardiovascular disease, DM = diabetes mellitus, GFR = glomerular filtration rate, HDL-C = high-density lipoprotein cholesterol, HTN = hypertension, LDL-C = low-density lipoprotein cholesterol, MI = myocardial infarction, NA = not applicable, NFMI = nonfatal myocardial infarction, NR = not reported, PAF = paroxysmal atrial fibrillation, PCr = plasma creatinine, PVD = peripheral vascular disease, SCr = serum creatinine, TC = total cholesterol, TG = triglycerides, TIA = transient ischemic attack, UK = United Kingdom, USA = United States of America. For complete study names, see Box 1.
*
Hypertension is assumed to be treated, unless inclusion criteria indicated untreated or uncontrolled hypertension, or no use of antihypertensive medications.
†
Factorial design: statin treatment groups combined, control groups combined.
‡
Includes angina, myocardial infarction, revascularization, stroke and peripheral arterial disease.
**
Includes angina, intermittent claudication, stroke, transient ischemic attack and abnormality on electrocardiogram.