Näytönastekatsaukset

What is the effectiveness of PCSK9 inhibitors for cardiovascular disease (CVD) prevention?

Näytönastekatsaukset

24.9.2026

Miia Aro

Level of evidence: A

In adult, high risk CVD patients with high LDL-C, PCSK9 inhibitors alirocumab and evolocumab in addition to statin or life-style counselling reduce the risk of cardiovascular endpoint events (alirocumab events 11 % vs. 14 % in placebo, evolocumab 7 % vs. 11 %), any myocardial infarction (alirocumab events 10 % vs. 12 % in placebo, evolocumab 3.2 % vs. 4.5 %), or any stroke (alirocumab events 1.1% vs. 1.6 % in placebo, evolocumab 1.5 % vs. 1.9 %).

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.

Table 1. Description of the included studies
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 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 »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

Table 2. Additional comments for included studies
Reference	Comments
«Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 »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

Table 3. Composite endpoint of CVD, defined as urgent coronary revascularisation, unstable angina pectoris, non-fatal and fatal myocardial infarction, non-fatal and fatal stroke, and CHD death.
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 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 »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)	6-36 months	1049 (7%)	1639 (11%)	0.84 (0.78, 0.91)

Table 4. All-cause mortality
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 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 »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)	6-36 months	449 (3.02 %)	430 (2.95 %)	1.04 (0.91,1.19)

Table 5. Myocardial infarction
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 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 »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)	6-36 months	479 (3.2 %)	653 (4.5 %)	0.72 (0.64,0.82)

Table 6. Any stroke
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 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 »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)	6-36 months	209 (1.5%)	265 (1.9%)	0.79 (0.65, 0.94)

References

Schmidt AF, Carter JL, Pearce LS, ym. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;10(10):CD011748 «PMID: 33078867»PubMed