Alirocumab reduces the risk of CVD with absolute difference of 3% compared to placebo, and in evolocumab with 4%. In addition, alirocumab reduces all-cause mortality in these patients but evolocumab did not. However, the follow-up times were quite short. There is very limited evidence on any potential safety issues or adverse effects of both evolocumab and alirocumab.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias «Additional comments for included studies...»2 |
|---|---|---|---|---|---|
| SR=systematic review, RCT=randomised controlled trial, CVD=cardiovascular disease | |||||
| «Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monocl...»1 | SR | 24 RCTs with data on 60 997 participants. People at high risk of CVD (history of CVD or high LDL-C despite treatment) in outpatient settings. | Alirocumab or evolocumab vs. placebo or active treatment | 1.CVD endpoint 2.All-cause mortality 3.Myocardial infarction 4.Any stroke |
Low |
| Reference | Comments |
|---|---|
| «Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monocl...»1 | 18 trials studied alirocumab and 6 evolocumab. All participants received background lipid-lowering treatment or lifestyle counselling. Six alirocumab studies used an active treatment comparison group (the remaining used placebo), and 3 evolocumab trials used active comparison. Follow-up ranged from 6 to 36 months for the comparisons with placebo and from 6 to 12 months for comparisons with active treatment. Most of the available studies preferentially enrolled people with either established CVD or at a high risk already. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Odds ratio (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: high CVD=cardiovascular disease; CHD=coronary heart disease; I=intervention; C=comparison; CI=confidence interval |
|||||
| «Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monocl...»1 | alirocumab 10 studies, 23868 patients (12770/11098) |
6-36 months | 1411 (11 %) | 1531 (14%) | 0.87 (0.80,0.94) |
| evolocumab. 3 studies, 29432 patients (14867/14565) |
1049 (7%) | 1639 (11%) | 0.84 (0.78, 0.91) | ||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Odds Ratio (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision and indirectness (short follow-up time). I=intervention; C=comparison; CI=confidence interval |
|||||
| «Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monocl...»1 | alirocumab 12 studies, 24797 patients (13390/11407) |
6-36 months | 352 (2.6 %) | 408 (3.6 %) | 0.83 (0.72,0.96) |
| evolocumab 3 studies, 29432 patients (14867/14565) |
449 (3.02 %) | 430 (2.95 %) | 1.04 (0.91,1.19) | ||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Odds ratio (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: high I=intervention; C=comparison; CI=confidence interval |
|||||
| «Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monocl...»1 | alirocumab 9 studies, 23352 patients (12369/10983) |
6-36 months | 1221 (10 %) | 1372 (12 %) | 0.86 (0.79,0.94) |
| evolocumab 3 studies, 29432 patients (14867/14565) |
479 (3.2 %) | 653 (4.5 %) | 0.72 (0.64,0.82) | ||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Odds Ratio (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: high I=intervention; C=comparison; CI=confidence interval |
|||||
| «Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monocl...»1 | alirocumab 8 studies, 22835 patients (12024/10811) |
6-36 months | 135 (1.1%) | 176 (1.6%) | 0.73 (0.58,0.91) |
| evolocumab 2 studies, 28531 patients (14268/14263) |
209 (1.5%) | 265 (1.9%) | 0.79 (0.65, 0.94) | ||