| pathology | Benefit (demonstrated or suggested) and harm | | | |
|---|
| acute coronary syndrome | superior to placebo (on top statins) in terms of CV events (fatal and non fatal) in IMPROVE-IT, 2014 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| IMPROVE-IT, 2014 | vs placebo (on top statins) | CV events (fatal and non fatal) 0.94 [0.89; 0.99] Demonstrated Major coronary event
0.87 [0.80; 0.95] | | all cause death or CV event 0.95 [0.90; 1.00] all cause mortality
0.99 [0.91; 1.07] Death from coronary heart disease 0.96 [0.84; 1.09] Death from cardiovascular causes 1.00 [0.89; 1.13] stroke 0.86 [0.73; 1.01] |
| Trial | Treatments | Patients | Method |
|---|
| IMPROVE-IT, 2014 | 10 mg/day of ezetimibe and 40 mg/day of simvastatin (n=9067) vs. simvastatin 40 mg/day (n=9077) If LDL-C response is inadequate, the dose of simvastatin may be increased to 80 mg | subjects with stabilized high-risk acute coronary syndrome | double blind Parallel groups Sample size: 9067/9077 Primary endpoint: CV death, MI, hospitalization for unstable angina, stroke and coronary revascularization FU duration: 5.68 years |
|
| cardiovascular prevention | superior to placebo (on top statins) in terms of CV events (fatal and non fatal) in IMPROVE-IT, 2014 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Enhance, 2008 | vs placebo (on top statins) | | | | | IMPROVE-IT, 2014 | vs placebo (on top statins) | CV events (fatal and non fatal) 0.94 [0.89; 0.99] Demonstrated Major coronary event
0.87 [0.80; 0.95] | | all cause death or CV event 0.95 [0.90; 1.00] all cause mortality
0.99 [0.91; 1.07] Death from coronary heart disease 0.96 [0.84; 1.09] Death from cardiovascular causes 1.00 [0.89; 1.13] stroke 0.86 [0.73; 1.01] | | SHARP, 2010 | vs placebo (on top statins) | CV events (fatal and non fatal) 0.87 [0.79; 0.95] | | Any incident cancer 0.99 [0.87; 1.12] all cause mortality
1.02 [0.95; 1.09] Major coronary event
0.92 [0.77; 1.10] fatal stroke 0.87 [0.63; 1.20] cancer 0.99 [0.87; 1.12] End-stage renal disease (ESRD) 0.97 [0.90; 1.04] | | SANDS, 2008 | vs placebo (on top statins) | | | adverse events 1.32 [0.98; 1.78] cardiovascular events 1.35 [0.55; 3.29] non cardiovascular death 0.49 [0.09; 2.65] | | ARBITER-HALTS 6, 2010 | vs placebo (on top statins) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Enhance, 2008 | ezetimibe 10mg + simvastatin daily (n=357) vs. simvastatin 80mg daily (n=363) | patients with familial hypercholesterolemia | double blind Parallel groups Sample size: 357/363 Primary endpoint: change in the mean carotid-artery intima–media thickness FU duration: 24 months | | IMPROVE-IT, 2014 | 10 mg/day of ezetimibe and 40 mg/day of simvastatin (n=9067) vs. simvastatin 40 mg/day (n=9077) If LDL-C response is inadequate, the dose of simvastatin may be increased to 80 mg | subjects with stabilized high-risk acute coronary syndrome | double blind Parallel groups Sample size: 9067/9077 Primary endpoint: CV death, MI, hospitalization for unstable angina, stroke and coronary revascularization FU duration: 5.68 years | | SHARP, 2010 | Simvastatin 20mg/Ezetimibe 10mg (n=4193) vs. placebo (n=4191) 3 arms: Simvastatin 20 mg, Simvastatin 20mg/Ezetimibe 10mg and placebo | patients with established chronic kidney disease (dialysis or pre-dialysis) | double-blind Parallel groups Sample size: 4193/4191 Primary endpoint: vascular events: cardiac death, MI, any stroke, or any revascularization FU duration: 4.9 years There is a certain incertitude concerning the primary endpoint (apparently changed by the Steering committe before the trial ended but this change was not endorsed by the sponsor)
Statistical analysis plan is not clear too, with or without the inclusion of patients initially allocated to simvastatin alone and re-randomized to either combination or placebo for the remainder of the study period | | SANDS, 2008 | aggressive targets of LDL-C of 70 mg/dL or lower and SBP of 115 mm Hg or lower (n=252) vs. standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower (n=247) | adults with type 2 diabetes | open Parallel groups Sample size: 252/247 Primary endpoint: common carotid artery intimal medial thickness (IMT) FU duration: 3 years | | ARBITER-HALTS 6, 2010 | addition of ezetimibe (10 mg/daily) to statin therapy (n=-9) vs. extended-release niacin 2000 mg/daily (n=-9) | patients at high risk for vascular disease but with LDL-cholesterol levels <100 mg/dL and moderately low HDL-cholesterol levels (<50 mg/dL) | open Parallel groups Sample size: -9/-9 Primary endpoint: carotid IMT FU duration: 14 months stopped early on the basis of a prespecified interim analysis showing that niacin was superior to ezetimibe on the end point of change in the carotid IMT |
|
| diabetes type 2 | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SANDS, 2008 | vs standard teatment | | | adverse events 1.32 [0.98; 1.78] cardiovascular events 1.35 [0.55; 3.29] non cardiovascular death 0.49 [0.09; 2.65] |
| Trial | Treatments | Patients | Method |
|---|
| SANDS, 2008 | aggressive targets of LDL-C of 70 mg/dL or lower and SBP of 115 mm Hg or lower (n=252) vs. standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower (n=247) | adults with type 2 diabetes | open Parallel groups Sample size: 252/247 Primary endpoint: common carotid artery intimal medial thickness (IMT) FU duration: 3 years |
|
| familial hypercholesterolemia | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Enhance, 2008 | vs placebo (on top statins) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Enhance, 2008 | ezetimibe 10mg + simvastatin daily (n=357) vs. simvastatin 80mg daily (n=363) | patients with familial hypercholesterolemia | double blind Parallel groups Sample size: 357/363 Primary endpoint: change in the mean carotid-artery intima–media thickness FU duration: 24 months |
|
| post myocardial infarction | superior to placebo (on top statins) in terms of CV events (fatal and non fatal) in IMPROVE-IT, 2014 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| IMPROVE-IT, 2014 | vs placebo (on top statins) | CV events (fatal and non fatal) 0.94 [0.89; 0.99] Demonstrated Major coronary event
0.87 [0.80; 0.95] | | all cause death or CV event 0.95 [0.90; 1.00] all cause mortality
0.99 [0.91; 1.07] Death from coronary heart disease 0.96 [0.84; 1.09] Death from cardiovascular causes 1.00 [0.89; 1.13] stroke 0.86 [0.73; 1.01] |
| Trial | Treatments | Patients | Method |
|---|
| IMPROVE-IT, 2014 | 10 mg/day of ezetimibe and 40 mg/day of simvastatin (n=9067) vs. simvastatin 40 mg/day (n=9077) If LDL-C response is inadequate, the dose of simvastatin may be increased to 80 mg | subjects with stabilized high-risk acute coronary syndrome | double blind Parallel groups Sample size: 9067/9077 Primary endpoint: CV death, MI, hospitalization for unstable angina, stroke and coronary revascularization FU duration: 5.68 years |
|
