| treatment |
|
comparator |
All cause death | Coronary death | Coronary event | Cardiovascular death | stroke (fatal and non fatal) | myocardial infarction (fatal and non fatal) | cardiovascular events | Allergic reactions | serious adverse events | death from all causes as adverse event | cardiovascular events as adverse event | Muscle-related adverse events | Neurocognitive disorder | neurological SAE | myocardial infarction as adverse event | cardiovascular death as adverse event | unstable angina as adverse death |
|
|
| Alirocumab | cardiovascular prevention, in all type of patients | vs ezetimibe (on top statin) | - | - | - | - | - | - | - | - | NS | NS | - | - | - | - | - | NS | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | no data | | Coronary death | no data | | Coronary event | no data | | Cardiovascular death | no data | | stroke (fatal and non fatal) | no data | | myocardial infarction (fatal and non fatal) | no data | | cardiovascular events | no data | | Allergic reactions | no data | | serious adverse events | 0.65 [0.29 1.50] | p=1.00 | 0 | 410 | 2 | ODYSSEY OPTIONS I, ODYSSEY OPTIONS II, | | death from all causes as adverse event | 0.33 [0.03 3.17] | p=1.00 | 0 | 410 | 2 | ODYSSEY OPTIONS I, ODYSSEY OPTIONS II, | | cardiovascular events as adverse event | no data | | Muscle-related adverse events | no data | | Neurocognitive disorder | no data | | neurological SAE | no data | | myocardial infarction as adverse event | no data | | cardiovascular death as adverse event | 0.25 [0.03 2.28] | p=1.00 | 0 | 410 | 2 | ODYSSEY OPTIONS I, ODYSSEY OPTIONS II, | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| ODYSSEY OPTIONS I, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Ezetimibe 10 mg | high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg) | | ODYSSEY OPTIONS II, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Ezetimibe 10 mg | high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg) |
|
| Alirocumab | cardiovascular prevention, in all type of patients | vs ezetimibe alone | - | - | - | - | - | - | - | - | NS | NS | - | - | - | - | - | NS | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | no data | | Coronary death | no data | | Coronary event | no data | | Cardiovascular death | no data | | stroke (fatal and non fatal) | no data | | myocardial infarction (fatal and non fatal) | no data | | cardiovascular events | no data | | Allergic reactions | no data | | serious adverse events | 0.98 [0.06 16.12] | p=1.00 | 0 | 103 | 1 | ODYSSEY MONO, | | death from all causes as adverse event | 0.98 [0.02 50.39] | p=1.00 | 0 | 103 | 1 | ODYSSEY MONO, | | cardiovascular events as adverse event | no data | | Muscle-related adverse events | no data | | Neurocognitive disorder | no data | | neurological SAE | no data | | myocardial infarction as adverse event | no data | | cardiovascular death as adverse event | 0.98 [0.02 50.39] | p=1.00 | 0 | 103 | 1 | ODYSSEY MONO, | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| ODYSSEY MONO, | Alirocumab 75 mg Q2W | Ezetimibe 10 mg | hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy |
|
| Alirocumab | cardiovascular prevention, in all type of patients | vs placebo (on top statins) | by 15% | NS | by 12% [demonstrated] | NS | - | - | by 13% [demonstrated] | NS | NS | by 62% | NS | - | NS | NS | by 56% | by 62% | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | 0.85 [0.73 0.98] | p=0.04 | 0 | 18924 | 1 | ODYSSEY OUTCOMES, | | Coronary death | 0.92 [0.76 1.11] | p=1.00 | 0 | 18924 | 1 | ODYSSEY OUTCOMES, | | Coronary event | 0.88 [0.80 0.96] | p=0.04 | 0 | 18924 | 1 | ODYSSEY OUTCOMES, | | Cardiovascular death | 0.88 [0.74 1.05] | p=1.00 | 0 | 18924 | 1 | ODYSSEY OUTCOMES, | | stroke (fatal and non fatal) | no data | | myocardial infarction (fatal and non fatal) | no data | | cardiovascular events | 0.87 [0.81 0.94] | p=0.04 | 0 | 18924 | 1 | ODYSSEY OUTCOMES, | | Allergic reactions | 1.06 [0.79 1.41] | p=1.00 | 0 | 2341 | 1 | ODYSSEY Long-Term, | | serious adverse events | 0.98 [0.82 1.18] | p=1.00 | 0 | 3732 | 5 | ODYSSEY Long-Term, ODYSSEY Alternative, ODYSSEY HIGH FH , ODYSSEY COMBO, ODYSSEY COMBO II, | | death from all causes as adverse event | 0.38 [0.15 0.96] | p=0.04 | 0 | 3735 | 5 | ODYSSEY Long-Term, ODYSSEY Alternative, ODYSSEY HIGH FH , ODYSSEY COMBO, ODYSSEY COMBO II, | | cardiovascular events as adverse event | 0.91 [0.61 1.36] | p=1.00 | 0 | 2341 | 1 | ODYSSEY Long-Term, | | Muscle-related adverse events | no data | | Neurocognitive disorder | 2.28 [0.77 6.77] | p=1.00 | 0 | 2341 | 1 | ODYSSEY Long-Term, | | neurological SAE | 0.94 [0.62 1.43] | p=1.00 | 0 | 2341 | 1 | ODYSSEY Long-Term, | | myocardial infarction as adverse event | 0.44 [0.22 0.85] | p=0.04 | 0 | 2908 | 3 | ODYSSEY Long-Term, ODYSSEY Alternative, ODYSSEY COMBO, | | cardiovascular death as adverse event | 0.38 [0.18 0.77] | p=0.04 | 0 | 3735 | 5 | ODYSSEY Long-Term, ODYSSEY Alternative, ODYSSEY HIGH FH , ODYSSEY COMBO, ODYSSEY COMBO II, | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| ODYSSEY Long-Term, 2015 | alirocumab 150 mg as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. | placebo | patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy | | ODYSSEY Alternative, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Ezetimibe 10 mg | statin-intolerant patients | | ODYSSEY OUTCOMES, 2018 | Alirocumab (on top intensive or maximum-tolerated statin therapy) | placebo | Post-ACS patients (1 to 12 months)with elevated levels of atherogenic lipoproteins despite intensive or maximum-tolerated statin therapy | | ODYSSEY FH 1, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Placebo | patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy | | ODYSSEY FH 2, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Placebo | patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy | | ODYSSEY HIGH FH , | Alirocumab 150 mg Q2W | Placebo | patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy | | ODYSSEY COMBO, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Placebo | high cardiovascular risk patients on maximally tolerated statin therapy | | ODYSSEY COMBO II, | Alirocumab 75 mg with potential up-titration to 150 mg Q2W | Ezetimibe 10 mg | high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins |
|
| Evolocumab | cardiovascular prevention, in all type of patients | vs | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | no data | | Coronary death | no data | | Coronary event | no data | | Cardiovascular death | no data | | stroke (fatal and non fatal) | no data | | myocardial infarction (fatal and non fatal) | no data | | cardiovascular events | no data | | Allergic reactions | no data | | serious adverse events | no data | | death from all causes as adverse event | no data | | cardiovascular events as adverse event | no data | | Muscle-related adverse events | no data | | Neurocognitive disorder | no data | | neurological SAE | no data | | myocardial infarction as adverse event | no data | | cardiovascular death as adverse event | no data | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| MENDEl 2, | | | | | Mendel 1, 2012 | | | | | YUKAWA-1, 2014 | | | |
|
| Evolocumab | cardiovascular prevention, in all type of patients | vs ezetimibe alone | - | - | - | - | - | - | - | - | NS | NS | - | NS | - | - | - | - | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | no data | | Coronary death | no data | | Coronary event | no data | | Cardiovascular death | no data | | stroke (fatal and non fatal) | no data | | myocardial infarction (fatal and non fatal) | no data | | cardiovascular events | no data | | Allergic reactions | no data | | serious adverse events | 3.01 [0.83 10.93] | p=1.00 | 0 | 307 | 1 | GAUSS 2, | | death from all causes as adverse event | 2.01 [0.04 102.03] | p=1.00 | 0 | 307 | 1 | GAUSS 2, | | cardiovascular events as adverse event | no data | | Muscle-related adverse events | 1.85 [0.99 3.45] | p=1.00 | 0 | 307 | 1 | GAUSS 2, | | Neurocognitive disorder | no data | | neurological SAE | no data | | myocardial infarction as adverse event | no data | | cardiovascular death as adverse event | no data | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| GAUSS 2, | evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) | ezetimibe 10 mg | patients with statin intolerance |
|
| Evolocumab | cardiovascular prevention, in all type of patients | vs placebo | - | - | - | - | - | - | - | - | NS | NS | - | NS | - | - | - | - | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | no data | | Coronary death | no data | | Coronary event | no data | | Cardiovascular death | no data | | stroke (fatal and non fatal) | no data | | myocardial infarction (fatal and non fatal) | no data | | cardiovascular events | no data | | Allergic reactions | no data | | serious adverse events | 3.03 [0.16 57.91] | p=1.00 | 0 | 127 | 1 | GAUSS 1, | | death from all causes as adverse event | 0.34 [0.01 17.33] | p=1.00 | 0 | 127 | 1 | GAUSS 1, | | cardiovascular events as adverse event | no data | | Muscle-related adverse events | 0.81 [0.26 2.50] | p=1.00 | 0 | 127 | 1 | GAUSS 1, | | Neurocognitive disorder | no data | | neurological SAE | no data | | myocardial infarction as adverse event | no data | | cardiovascular death as adverse event | no data | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| GAUSS 1, 2012 | | | statin-intolerant patients |
|
| Evolocumab | cardiovascular prevention, in all type of patients | vs placebo (on top statins) | NS | - | - | NS | by 21% | by 27% | by 20% [demonstrated] | - | NS | NS | NS | NS | NS | - | - | - | - | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| All cause death | 1.04 [0.91 1.19] | p=1.00 | 0 | 27564 | 1 | FOURIER, | | Coronary death | no data | | Coronary event | no data | | Cardiovascular death | 1.05 [0.88 1.25] | p=1.00 | 0 | 27564 | 1 | FOURIER, | | stroke (fatal and non fatal) | 0.79 [0.66 0.95] | p=0.04 | 0 | 27564 | 1 | FOURIER, | | myocardial infarction (fatal and non fatal) | 0.73 [0.65 0.82] | p=0.04 | 0 | 27564 | 1 | FOURIER, | | cardiovascular events | 0.80 [0.73 0.88] | p=0.04 | 0 | 27564 | 1 | FOURIER, | | Allergic reactions | no data | | serious adverse events | 1.03 [0.66 1.59] | p=1.00 | 0 | 3072 | 4 | DESCARTES, RUTHERFORD-1, LAPLACE 2, RUTHERFORD-2, | | death from all causes as adverse event | 0.61 [0.11 3.44] | p=1.00 | 0 | 3072 | 4 | DESCARTES, RUTHERFORD-1, LAPLACE 2, RUTHERFORD-2, | | cardiovascular events as adverse event | 1.55 [0.53 4.53] | p=1.00 | 0 | 2905 | 3 | DESCARTES, LAPLACE 2, RUTHERFORD-2, | | Muscle-related adverse events | 4.95 [0.63 39.21] | p=1.00 | 0 | 329 | 1 | RUTHERFORD-2, | | Neurocognitive disorder | 0.96 [0.08 11.52] | p=1.00 | 0 | 2004 | 2 | LAPLACE 2, RUTHERFORD-2, | | neurological SAE | no data | | myocardial infarction as adverse event | no data | | cardiovascular death as adverse event | no data | | unstable angina as adverse death | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients | Trial | Studied treatment | Control | Patients |
|---|
| DESCARTES, 2014 | evolocumab (420 mg) every 4 weeks | placebo | | | LAPLACE-TIMI 57, | subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, | placebo | | | RUTHERFORD-1, | AMG 145 350 mg, AMG 145 420 mg | placebo | heterozygous familial hypercholesterolemia patients | | LAPLACE 2, 2014 | evolucumab + statin | placebo + statin | | | RUTHERFORD-2, 2015 | subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly | placebo | heterozygous familial hypercholesterolaemia | | FOURIER, 2017 | evolocumab (either 140 mg every 2 weeks or 420 mg monthly) | placebo | patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy |
|
