Overview
Unverified · drafted by AI from the sources cited below
Definition
PCSK9 inhibitors are agents that inhibit Proprotein Convertase Subtilisin/Kexin Type 9, an enzyme that plays an important role in the degradation of low-density lipoprotein receptors.1 By inhibiting this enzyme, these agents favor low-density lipoprotein catabolism and reduce plasma low-density lipoprotein cholesterol levels.1
Treatment
Evolocumab, a PCSK9 inhibitor, significantly reduced low-density lipoprotein cholesterol by a mean difference of -57.73 mg/dL in a meta-analysis of 67,662 patients.1 In the FOURIER trial, 27 564 patients with atherosclerotic cardiovascular disease received evolocumab or placebo, with 6635 patients subsequently enrolling in an open-label extension.2 Another PCSK9 inhibitor, alirocumab, was evaluated at a dose of 150 mg in 300 patients with acute myocardial infarction.3 Investigational oral PCSK9 inhibitors have also been evaluated in trials including 949 participants.4 Additionally, in vivo CRISPR base-editing technologies are being investigated in ongoing clinical trials as a strategy to permanently reduce circulating PCSK9 levels following a single infusion.5
New research on PCSK9 inhibitors
Landmark trials
Primary results of 4 trials behind the evidence on pcsk9 inhibitors, as each trial’s own publication reports them.
Left of the line at 1 favours the intervention; square size tracks trial size.Favours the interventionNo significant differenceFavours the comparator
0.512
alirocumab vs placebo · 18,924 patients · N Engl J Med 2018
In patients who had an acute coronary syndrome 1 to 12 months earlier
Primary outcome: a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization
Live debates in PCSK9 inhibitors1
Ranked by heat on the board →Key papers
Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction
JAMA — Räber L
616 citations · 2022 · among the most cited on PCSK9 inhibitors
Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease
Circulation — O’Donoghue M
410 citations · 2022 · among the most cited on PCSK9 inhibitors
Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE
Circulation — Gaba P
186 citations · 2023 · among the most cited on PCSK9 inhibitors
Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
eLife
164 citations · 2021 · among the most cited on PCSK9 inhibitors
How this page is built
A clinical question appears here only when its condition matches this topic, an outcome and a comparator were extracted from the studies, at least two studies and a patient count are on file, and the certainty is low or higher.
Supports benefit, no benefit shown, and mixed describe the direction of the measured effect. No benefit shown means the evidence does not support a benefit. It is not a finding of harm. Too little evidence means the question did not clear that bar.
Study count, RCT count, and patient count are separate. The patient total adds only studies that are linked into a study family and whose sample size is not flagged as implausible. A reversal is listed only when at least one randomized trial sits on each side of the change.
The overview is drafted from the guideline recommendations, trials, papers, and questions on this page, and every sentence has to cite one of them. It stays unverified until an NPI-verified clinician or a Synapse admin approves it. Approving records that person's name.
