| pathology | Demonstrated benefit and harm | k | | | |
|---|
| acute coronary syndrome | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| A to Z, 2004 | simvastatin vs placebo | | | Death 0.90 [0.60; 1.35] fatal MI 0.62 [0.35; 1.11] Revascularisation 0.95 [0.74; 1.21] Non fatal acute MI 0.99 [0.77; 1.29] Stroke (fatal & non fatal) 0.79 [0.48; 1.29] Death from CHD 0.86 [0.57; 1.30] Major cardiovascular events 0.89 [0.77; 1.02] death, MI and stroke - 4 month 0.99 [0.80; 1.22] death, MI and stroke - 1 month 0.93 [0.71; 1.22] |
| Trial | Treatments | Patients | Method |
|---|
| A to Z, 2004 | Simvastatin, 40-80 mg early initiation (n=2265) vs. Placebo (n=2232) | patient with an acute coronary syndrome (ACS) | Double aveugle Parallel groups Sample size: 2265/2232 Primary endpoint: cardiovascular death, MI, rehospitalization for ACS or stroke FU duration: 4 months |
|
| aortic stenosis | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SEAS, 2008 | ezetimibe+simvastatin vs placebo | | | CV detah, aortic replacement, hospitalization for severe aortic stenosis 0.92 [0.82; 1.04] Death from any cause 1.03 [0.80; 1.34] Aortic-valve replacement 0.95 [0.82; 1.09] CV death 0.83 [0.57; 1.20] |
| Trial | Treatments | Patients | Method |
|---|
| SEAS, 2008 | simvastatin 40mg plus ezetimibe 10 mg daily (n=944) vs. placebo (n=929) | patients with mild-tomoderate,
asymptomatic aortic stenosis | double blind Parallel groups Sample size: 944/929 Primary endpoint: aortic-valve and cardiovascular events FU duration: 52.2 mo |
|
| CABG surgery | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Christenson, 1999 | preoperative simvastatin vs no treatment | | | all-cause mortality NaN [NaN; NaN] MI 0.00 [0.00; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Christenson, 1999 | preoperative simvastatin 20 mg/d, stated 4 weeks before surgery (n=40) vs. no statins (n=37) | patients with hypercholesterolemia (total cholesterol > or =6.2 mmol/l) planned for CABG | Sample size: 40/37 Primary endpoint: FU duration: 7 days |
|
| cardiovascular prevention | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SEAS, 2008 | ezetimibe+simvastatin vs placebo | | | CV detah, aortic replacement, hospitalization for severe aortic stenosis 0.92 [0.82; 1.04] Death from any cause 1.03 [0.80; 1.34] Aortic-valve replacement 0.95 [0.82; 1.09] CV death 0.83 [0.57; 1.20] |
| Trial | Treatments | Patients | Method |
|---|
| SEAS, 2008 | simvastatin 40mg plus ezetimibe 10 mg daily (n=944) vs. placebo (n=929) | patients with mild-tomoderate,
asymptomatic aortic stenosis | double blind Parallel groups Sample size: 944/929 Primary endpoint: aortic-valve and cardiovascular events FU duration: 52.2 mo |
|
| cardiovascular prevention | versus placebo or control simvastatin superior to placebo in terms of all cause deaths in HPS, 2002 (secondary prevention patients) simvastatin superior to placebo in terms of all cause deaths in 4S, 1994 (secondary prevention patients) | 16 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HPS (diabetic sub group), 2002 | simvastatin vs placebo | Critère de jugement principal de l'étude 0.81 [0.73; 0.89] Evénement coronarien majeur 0.74 [0.64; 0.86] AVC 0.77 [0.63; 0.95] Cv events (CV death, MI, stroke) 0.81 [0.73; 0.89] | | | | 4S (diabetic sub group), 1999 | simvastatin vs placebo | Critère de jugement principal de l'étude 0.63 [0.47; 0.83] Evénement coronarien majeur 0.63 [0.47; 0.83] | | Décès toutes causes 0.79 [0.49; 1.28] | | simvastatin vs placebo | | | | | simvastatin vs placebo | | | | | MAAS, 1994 | simvastatin vs placebo | | | all cause deaths 0.35 [0.11; 1.09] coronary deaths 0.78 [0.21; 2.86] Rhabdomyolyses NaN [NaN; NaN] non cardiovascular death 0.00 [0.00; NaN] | | HPS, 2002 | simvastatin vs placebo | all cause deaths 0.88 [0.82; 0.94] Demonstrated coronary deaths 0.83 [0.75; 0.92] coronary events 0.74 [0.68; 0.80] cardiovascular death 0.83 [0.76; 0.91] MI non fatal 0.62 [0.55; 0.71] stroke (fatal et non fatal) 0.76 [0.67; 0.86] Infarctus non mortel et décès coronariens 0.74 [0.68; 0.80] | | Pancreatitis 0.80 [0.51; 1.27] décès par cancer 1.04 [0.90; 1.20] Haemorrhagic strokes 0.96 [0.66; 1.41] fatal stroke 0.81 [0.62; 1.05] Rhabdomyolyses 1.67 [0.40; 6.97] Myopathies 2.50 [0.78; 7.97] incident diabetes 1.15 [0.98; 1.35] | | 4S, 1994 | simvastatin vs placebo | all cause deaths 0.71 [0.59; 0.85] Demonstrated coronary deaths 0.59 [0.47; 0.74] coronary events 0.69 [0.62; 0.77] cardiovascular death 0.66 [0.53; 0.81] MI non fatal 0.67 [0.58; 0.77] stroke (fatal et non fatal) 0.71 [0.53; 0.97] cardiac death 0.59 [0.47; 0.74] cardiovascular events 0.74 [0.67; 0.81] | | Pancreatitis 0.71 [0.23; 2.25] décès par cancer 0.94 [0.59; 1.51] Haemorrhagic strokes 0.00 [0.00; NaN] fatal stroke 1.17 [0.54; 2.52] non cardiovascular death 0.94 [0.63; 1.40] incident diabetes 1.03 [0.83; 1.27] | | A to Z, 2004 | simvastatin vs placebo | | | Death 0.90 [0.60; 1.35] fatal MI 0.62 [0.35; 1.11] Revascularisation 0.95 [0.74; 1.21] Non fatal acute MI 0.99 [0.77; 1.29] Stroke (fatal & non fatal) 0.79 [0.48; 1.29] Death from CHD 0.86 [0.57; 1.30] Major cardiovascular events 0.89 [0.77; 1.02] death, MI and stroke - 4 month 0.99 [0.80; 1.22] death, MI and stroke - 1 month 0.93 [0.71; 1.22] | | Node, 2003 | simvastatin vs placebo | | | hospitalization for heart failure 1.13 [0.07; 17.02] All cause death NaN [NaN; NaN] cardiovascular death NaN [NaN; NaN] | | Hong, 2005 | simvastatin vs control | | | cardiovascular death 0.26 [0.05; 1.20] non fatal MI 0.45 [0.08; 2.39] | | CIS, 1997 | simvastatin vs placebo | | | all cause deaths 0.24 [0.03; 2.14] coronary deaths 0.48 [0.04; 5.28] coronary events 0.76 [0.41; 1.44] MI non fatal 0.19 [0.02; 1.64] non cardiovascular death 0.00 [0.00; NaN] | | 4S (elderly subgroup), 1997 | simvastatin vs placebo | All cause mortality 0.68 [0.51; 0.90] Coronary Heart Disease Mortality 0.59 [0.41; 0.83] Revascularization 0.62 [0.45; 0.86] Nonfatal Myocardial Infarction 0.71 [0.55; 0.90] | | | | HPS (elderly subgroup), 2002 | simvastatin vs placebo | All cause mortality 0.88 [0.81; 0.95] Coronary Heart Disease Mortality 0.83 [0.75; 0.93] stroke 0.71 [0.61; 0.83] | | | | HPS (post troke sub group), 2004 | simvastatin vs placebo | Major cardiovascular event 0.79 [0.66; 0.95] | | Nonfatal or fatal stroke 0.99 [0.76; 1.29] | | HPS (diabetic primary prevention sub group), 2003 | simvastatin vs placebo | | | | | HPS (women subgroup) , 2002 | Simvastatin vs placebo | CHD events 0.76 [0.62; 0.94] | | |
| Trial | Treatments | Patients | Method |
|---|
| HPS (diabetic sub group), 2002 | simvastatin 40mg daily (n=2978) vs. placebo (n=2985) | Men and women diabetes aged about 40–80 years with non-fasting
blood total cholesterol concentrations of at least
3·5 mmol/L (135 mg/dL) | double blind Parallel groups Sample size: 2978/2985 Primary endpoint: FU duration: | | 4S (diabetic sub group), 1999 | simvastatin (n=251) vs. placebo (n=232) | diabetic men
and women aged 35 to 70 years with previous MI or active,
stable angina pectoris and with serum total cholesterol
level between 5.5 to 8.0 mmol/L and serum
triglyceride level <=2.5 mmol/L | double blind Parallel groups Sample size: 251/232 Primary endpoint: FU duration: 5.4y | | Mondillo, 2003 | simvastatine: 40 mg/ jour pendant 6 mois. (n=43) vs. placebo (n=43) | Stade de la maladie: II. | Double aveugle Parallel groups Sample size: 43/43 Primary endpoint: périmètre de marche( maximal, sans douleur) FU duration: 6 mois | | Aronow , 2003 | simvastatine 40 mg/j (n=34) vs. placebo (n=35) | Stade II | Non déterminable Parallel groups Sample size: 34/35 Primary endpoint: périmètre de marche FU duration: 1 an | | MAAS, 1994 | simvastatin 20 mg daily (n=193) vs. placebo (n=188) | patients with coronary heart disease | double blind Parallel groups Sample size: 193/188 Primary endpoint: QCA FU duration: 4 y | | HPS, 2002 | simvastatin 40 mg/d (n=10269) vs. placebo (n=10267) | adults (aged 40-80 years) with coronary disease, other occlusive arterial disease, or diabete | double blind Factorial plan Sample size: 10269/10267 Primary endpoint: all cause death FU duration: 5 years | | 4S, 1994 | simvastatin 20 or 40 mg/d, target CT between 3 et 5.2 mmol/l (n=2221) vs. placebo (n=2223) (37 % des patients à 40 mg/j); simvastatine 10 mg/j pour 2 patients | patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet | double blind Parallel groups Sample size: 2221/2223 Primary endpoint: all cause death FU duration: 5.4 years | | A to Z, 2004 | Simvastatin, 40-80 mg early initiation (n=2265) vs. Placebo (n=2232) | patient with an acute coronary syndrome (ACS) | Double aveugle Parallel groups Sample size: 2265/2232 Primary endpoint: cardiovascular death, MI, rehospitalization for ACS or stroke FU duration: 4 months | | Node, 2003 | simvastatin 10mg/d (n=24) vs. placebo (n=27) | patients with symptomatic, nonischemic, dilated cardiomyopathy | Sample size: 24/27 Primary endpoint: FU duration: | | Hong, 2005 | simvastatin (n=106) vs. no treatment (n=96) | patients with ischemic heart failure who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (left ventricular [LV] ejection fraction <40%) | open Parallel groups Sample size: 106/96 Primary endpoint: none FU duration: 1 year | | CIS, 1997 | simvastatin 40 mg (n=129) vs. placebo (n=125) | men with documented coronary artery disease and hypercholesterolaemia | double blind Parallel groups Sample size: 129/125 Primary endpoint: mean change of minimum lumen diameter FU duration: 2.3 years | | 4S (elderly subgroup), 1997 | Simvastatin 20-40mg (n=518) vs. (n=503) | MI 6 months or stable angina, subgroup of age 65-70 y | double blind parallel groups Sample size: 518/503 Primary endpoint: FU duration: 5.4y | | HPS (elderly subgroup), 2002 | Simvastatin 40mg (n=5366) vs. (n=5331) | Vascular disease or diabetes, subgroup of age 65-80 y | double blind parallel groups Sample size: 5366/5331 Primary endpoint: FU duration: 5.0y | | HPS (post troke sub group), 2004 | simvastatin 40mg daily (n=920) vs. placebo (n=900) | adults with cerebrovascular disease, total cholesterol >=3·5 mmol/L and without coronaro disease (n=1820) | double blind Parallel groups Sample size: 920/900 Primary endpoint: FU duration: | | HPS (diabetic primary prevention sub group), 2003 | simvastatin 40 mg/d (n=1455) vs. placebo (n=1457)
| adults (aged 40-80 years) with diabetes (primary prevention subgroup)
| double blind Parallel groups Sample size: 1455/1457 Primary endpoint: All cause death FU duration: 5 years
| | HPS (women subgroup) , 2002 | Simvastatin 40 mg (n=914) vs. placebo (n=902) | UK adults (aged 40-80 years) with coronary disease,other occlusive arterial disease, or diabetes - subgroup of women without CHD | double blind Parallel groups Sample size: 914/902 Primary endpoint: mortality FU duration: 5 y |
|
| cardiovascular prevention | versus ezetimibe No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Landmesser, 2005 | simvastatin vs ezetimibe | | | |
| Trial | Treatments | Patients | Method |
|---|
| Landmesser, 2005 | simvastatin 10mg/d (n=10) vs. ezetimibe 10mg/d (n=10) | patients with chronic heart failure | Sample size: 10/10 Primary endpoint: FU duration: |
|
| cardiovascular prevention | versus statin No demonstrated result for efficacy simvastatin high dose inferior to simvastatin in terms of Rhabdomyolyses in SEARCH, 2010 (secondary prevention patients) | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SEARCH, 2010 | simvastatin high dose vs simvastatin | MI non fatal 0.86 [0.75; 0.98] | Rhabdomyolyses 17.67 [5.53; 56.52] | Pancreatitis 0.66 [0.37; 1.17] all cause deaths 1.00 [0.92; 1.08] coronary deaths 1.02 [0.90; 1.16] coronary events 0.97 [0.90; 1.04] cardiovascular death 0.99 [0.89; 1.11] décès par cancer 0.92 [0.78; 1.09] CV events (including revascularization) 0.95 [0.89; 1.01] fatal stroke 0.85 [0.60; 1.21] stroke (fatal et non fatal) 0.91 [0.77; 1.08] cardiac death 1.02 [0.90; 1.16] cardiovascular events 0.95 [0.89; 1.01] non cardiovascular death 1.00 [0.87; 1.14] |
| Trial | Treatments | Patients | Method |
|---|
| SEARCH, 2010 | simvastatin 80 mg daily (n=6031) vs. simvastatin 20mg daily (n=6033) factorial design with folic acid and vitamin B12 | MI survivors | Parallel groups Sample size: 6031/6033 Primary endpoint: coronary death, myocardial infarction, stroke, or arterial revascularisation FU duration: 6.7 years (mean) |
|
| diabetes type 2 | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HPS (diabetic sub group), 2002 | simvastatin vs placebo | Critère de jugement principal de l'étude 0.81 [0.73; 0.89] Evénement coronarien majeur 0.74 [0.64; 0.86] AVC 0.77 [0.63; 0.95] Cv events (CV death, MI, stroke) 0.81 [0.73; 0.89] | | | | 4S (diabetic sub group), 1999 | simvastatin vs placebo | Critère de jugement principal de l'étude 0.63 [0.47; 0.83] Evénement coronarien majeur 0.63 [0.47; 0.83] | | Décès toutes causes 0.79 [0.49; 1.28] |
| Trial | Treatments | Patients | Method |
|---|
| HPS (diabetic sub group), 2002 | simvastatin 40mg daily (n=2978) vs. placebo (n=2985) | Men and women diabetes aged about 40–80 years with non-fasting
blood total cholesterol concentrations of at least
3·5 mmol/L (135 mg/dL) | double blind Parallel groups Sample size: 2978/2985 Primary endpoint: FU duration: | | 4S (diabetic sub group), 1999 | simvastatin (n=251) vs. placebo (n=232) | diabetic men
and women aged 35 to 70 years with previous MI or active,
stable angina pectoris and with serum total cholesterol
level between 5.5 to 8.0 mmol/L and serum
triglyceride level <=2.5 mmol/L | double blind Parallel groups Sample size: 251/232 Primary endpoint: FU duration: 5.4y |
|
| heart failure | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Node, 2003 | simvastatin vs placebo | | | hospitalization for heart failure 1.13 [0.07; 17.02] All cause death NaN [NaN; NaN] cardiovascular death NaN [NaN; NaN] | | Hong, 2005 | simvastatin vs control | | | cardiovascular death 0.26 [0.05; 1.20] non fatal MI 0.45 [0.08; 2.39] |
| Trial | Treatments | Patients | Method |
|---|
| Node, 2003 | simvastatin 10mg/d (n=24) vs. placebo (n=27) | patients with symptomatic, nonischemic, dilated cardiomyopathy | Sample size: 24/27 Primary endpoint: FU duration: | | Hong, 2005 | simvastatin (n=106) vs. no treatment (n=96) | patients with ischemic heart failure who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (left ventricular [LV] ejection fraction <40%) | open Parallel groups Sample size: 106/96 Primary endpoint: none FU duration: 1 year |
|
| heart failure | versus ezetimibe No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Landmesser, 2005 | simvastatin vs ezetimibe | | | |
| Trial | Treatments | Patients | Method |
|---|
| Landmesser, 2005 | simvastatin 10mg/d (n=10) vs. ezetimibe 10mg/d (n=10) | patients with chronic heart failure | Sample size: 10/10 Primary endpoint: FU duration: |
|
| peripheral vascular diseases | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| simvastatin vs placebo | | | | | simvastatin vs placebo | | | | | simvastatin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| HPS (sub group), 2002 | simvastatine 40 mg/ jour pendant 5 ans (n=10269) vs. placebo (n=10267) | 32.85% des patients présentaient une artériopathie des membres inférieurs 63603 ont été initialement recrutés, et 32145 ont commencé la période de prérandomisation. | Double aveugle Factorial plan Sample size: 10269/10267 Primary endpoint: mortalité / évènements vasculaires FU duration: 5 ans une phase de prérandomisation "run-in" incluant 4 semaines de placebo suivies de 4-6 semaines de simvastatine 40 mg/ jours permet d'exclure secondairement les sujets non éligibles ou les non compliants
La randomisation a été centralisée par téléphone.
les analyses sont en ITT | | Mondillo, 2003 | simvastatine: 40 mg/ jour pendant 6 mois. (n=43) vs. placebo (n=43) | Stade de la maladie: II. | Double aveugle Parallel groups Sample size: 43/43 Primary endpoint: périmètre de marche( maximal, sans douleur) FU duration: 6 mois | | Aronow , 2003 | simvastatine 40 mg/j (n=34) vs. placebo (n=35) | Stade II | Non déterminable Parallel groups Sample size: 34/35 Primary endpoint: périmètre de marche FU duration: 1 an |
|
| post myocardial infarction | versus placebo or control simvastatin superior to placebo in terms of all cause deaths in 4S, 1994 (secondary prevention patients) | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| 4S, 1994 | simvastatin vs placebo | all cause deaths 0.71 [0.59; 0.85] Demonstrated coronary deaths 0.59 [0.47; 0.74] coronary events 0.69 [0.62; 0.77] cardiovascular death 0.66 [0.53; 0.81] MI non fatal 0.67 [0.58; 0.77] stroke (fatal et non fatal) 0.71 [0.53; 0.97] cardiac death 0.59 [0.47; 0.74] cardiovascular events 0.74 [0.67; 0.81] | | Pancreatitis 0.71 [0.23; 2.25] décès par cancer 0.94 [0.59; 1.51] Haemorrhagic strokes 0.00 [0.00; NaN] fatal stroke 1.17 [0.54; 2.52] non cardiovascular death 0.94 [0.63; 1.40] incident diabetes 1.03 [0.83; 1.27] |
| Trial | Treatments | Patients | Method |
|---|
| 4S, 1994 | simvastatin 20 or 40 mg/d, target CT between 3 et 5.2 mmol/l (n=2221) vs. placebo (n=2223) (37 % des patients à 40 mg/j); simvastatine 10 mg/j pour 2 patients | patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet | double blind Parallel groups Sample size: 2221/2223 Primary endpoint: all cause death FU duration: 5.4 years |
|
| post stroke | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HPS (post troke sub group), 2004 | simvastatin vs placebo | Major cardiovascular event 0.79 [0.66; 0.95] | | Nonfatal or fatal stroke 0.99 [0.76; 1.29] |
| Trial | Treatments | Patients | Method |
|---|
| HPS (post troke sub group), 2004 | simvastatin 40mg daily (n=920) vs. placebo (n=900) | adults with cerebrovascular disease, total cholesterol >=3·5 mmol/L and without coronaro disease (n=1820) | double blind Parallel groups Sample size: 920/900 Primary endpoint: FU duration: |
|
