← PCSK9 inhibitors × cardiovascular events

SynthesisAdvances in therapy2020

Efficacy and Safety of PCSK9 Monoclonal Antibodies in Patients at High Cardiovascular Risk: An Updated Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

Guangyan Mu et al.PubMed ↗Publisher ↗

  • PCSK9 monoclonal antibodieslooks bad hereHigher injection site reactions, no clear effect on deaths.Randomised, large.
  • Alirocumablooks good hereFewer major cardiovascular events.Randomised, large.
  • Evolocumablooks good hereFewer major cardiovascular events.Randomised, large.
  • Evolocumab 140 mg every 2 weekslooks good hereLower absolute change in LDL-C levels, lower percent change in LDL-C levels.Correlation only, not a test of it.

What the trial testedrandomised · 57,090 people · 2020

Randomised vs placebo or active drugs

Raised injection site reactions

+54%+38% to +71%

PCSK9 monoclonal antibodies vs placebo or active drugs

Bigger than 7 in 10 for adverse events & safety

As reported

RR 1.54, 95% CI 1.38–1.71

Randomised vs placebo or active drugs

Reduced major cardiovascular events

−11%−17% to −5%

alirocumab vs placebo or active drugs

Bigger than 2 in 10 for cardiovascular events

As reported

RR 0.89, 95% CI 0.83–0.95

Randomised vs placebo or active drugs

Reduced major cardiovascular events

−14%−20% to −8%

evolocumab vs placebo or active drugs

Bigger than 3 in 10 for cardiovascular events

As reported

RR 0.86, 95% CI 0.80–0.92

One subgroup

May have reduced major cardiovascular events in secondary preventive patients

−12%−18% to −5%

alirocumab vs placebo or active drugs, in secondary preventive patients

Bigger than 2 in 10 for cardiovascular events

As reported

RR 0.88, 95% CI 0.82–0.95

What moved togetherboth groups pooled, not the treatment’s effect

Correlation, not cause

Went with fewer cardiovascular events

−14%−20% to −8%

Bigger than 3 in 10 for cardiovascular events

As reported

RR 0.86, 95% CI 0.80–0.92

Correlation, not cause

Evolocumab 140 mg every 2 weeks went with lower absolute change in LDL-C levels

−0.36−0.71 to −0.01

evolocumab 140 mg every 2 weeks vs alirocumab 150 mg every 2 weeks

As reported

difference −0.36, 95% CI −0.71 to −0.01

Correlation, not cause

Evolocumab 140 mg every 2 weeks went with lower percent change in LDL-C levels

−19.5−32.0 to −7.04

evolocumab 140 mg every 2 weeks vs alirocumab 150 mg every 2 weeks

As reported

difference −19.5, 95% CI −32.0 to −7.04

+1 more in the walkthrough ↓

Who was studied, and how

57,090people with cardiovascular disease, in this paper

The trial randomly assignedassigned by chance

PCSK9 monoclonal antibodies
placebo or active drugs

Raised injection site reactions+54%

No clear effect on deaths−12%

randomised

The trial randomly assignedassigned by chance

alirocumab
placebo or active drugs

Reduced major cardiovascular events−11%

randomised

the abstract, start to end

… site reactions (relative risks (RR) 1.54; 95% CI 1.38-1.71; P < 0.001).

Both alirocumab (RR 0.89; 95% CI 0.83-0.95; P < 0.001) and evolocumab (RR 0.86; 95% CI 0.80-0.92; P < 0.001) were associated with a lower risk of major cardiovascular events (MACEs), especially in secondary preventive patients (alirocumab group: RR 0.88; 95% CI 0.82-0.95; P < 0.001; evolocumab group: RR 0.86; 95% CI 0.80-0.92; P < 0.001).

… of all-cause mortality was found (RR 0.88; 95% CI 0.72-1.07; P = 0.182).

… (weighted mean differences (WMD) - 0.36; 95% confidence interval (CI) - 0.71 to - 0.01; P = 0.041) and percent change (WMD - 19.53; 95% CI - 32.02 to - 7.04; …

← favours treatmentfavours comparator →
could be chance
Injection site reactionsPCSK9 monoclonal antibodies vs placebo or active drugs
RR 1.541.38–1.71
Major cardiovascular events (MACEs)alirocumab vs placebo or active drugs
RR 0.890.83–0.95
Cardiovascular events
RR 0.860.80–0.92
Major cardiovascular events (MACEs)evolocumab vs placebo or active drugs
RR 0.860.80–0.92
Major cardiovascular events (MACEs)alirocumab vs placebo or active drugs, in secondary preventive patients
RR 0.880.82–0.95
All-cause mortalityPCSK9 monoclonal antibodies vs placebo or active drugs
RR 0.880.72–1.07
Absolute change in LDL-C levelsevolocumab 140 mg every 2 weeks vs alirocumab 150 mg every 2 weeks
−0.36−0.71 to −0.01
Percent change in LDL-C levelsevolocumab 140 mg every 2 weeks vs alirocumab 150 mg every 2 weeks
−19.5−32.0 to −7.04
PCSK9 inhibitorsLipidsCardiovascular eventsAll-cause mortalityAdverse events & safety

PCSK9 inhibitors × cardiovascular eventshelps?settled

unlikelylikely
1.00not counted

PCSK9 inhibitors × all-cause mortalityhelps?replicated

unlikelylikely
1.00not counted

PCSK9 inhibitors × adverse events & safetyharms?mixed

unlikelylikely
0.00not counted
← favours treatmentfavours comparator →
more certainless certain
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22 papers cite it

2020
2021
2022
2023
2024
2025
2026
this paperpooled ittrialcites it
Full record →Abstract, authors, funding and every citing paper · PMID 32108309