SYSTEMATIC REVIEW article
Front. Cardiovasc. Med.
Sec. Lipids in Cardiovascular Disease
The Lipid Lowering Efficacy of PCSK9 Inhibitors Alone vs. Statins Alone: A Meta-Analysis
Provisionally accepted
- 1California University of Science and Medicine, San Bernardino, United States
- 2Statistics Core, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, United States
- 3Comprehensive Stroke Center and Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, United States
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Background: PCSK9 inhibitors (PCSK9is) have been developed as an add-on therapy to maximally tolerated statin therapy. To date, high prices have precluded their use as first-line agents but, in the near future, PCSK9is will go off patent protection, reducing cost barriers and making them first-line agent candidates before statins. This study's objective was to evaluate the lipid lowering efficacy of PCSK9i monotherapy compared with high intensity statin monotherapy as a first line agent. Methods: This meta-analysis adhered to PRISMA guidelines. A systematic literature review identified all RCTs of: 1) PCSK9i vs control in which data were available on a patient subgroup receiving PCSK9i monotherapy (predominantly due to total statin intolerance); and 2) high-intensity statins vs control, with high-intensity statins defined as atorvastatin 40 or 80 mg daily or rosuvastatin 20 or 40 mg daily. The primary outcome was mean percent change in serum low density lipoprotein cholesterol (LDL-C). Secondary outcomes evaluated high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), and apolipoprotein B (ApoB). Results: Five trials (766 patients) were identified for PCSK9is and 49 trials (19,603 patients) for statins. The mean age (±SD) was 57.5±5.1 years in PCSK9i trials and 60.2±2.3 years in statin trials, with a higher proportion of women enrolled in the PCSK9i group (54.3% vs. 39.9%). Compared to all high-intensity statin regimens combined, PCSK9is showed significantly greater reductions in LDL-C (-52.4% vs. -46.6%, p=0.03), ApoB (-43.3% vs. -32.8%, p=0.005), and increases in HDL-C (8.0% vs. 4.4%, p=0.02). Statin agent subgroup analysis found PCSK9is were superior to atorvastatin and comparable to rosuvastatin in increasing HDL-C and reducing LDL-C, ApoB, and TC, and inferior to atorvastatin and rosuvastatin in reducing TG. Conclusions: PCSK9i monotherapy is superior to atorvastatin and comparable to rosuvastatin in improving LDL-C, HDL-C, TC, and ApoB, though inferior in reducing TG. These findings confirm that PCSK9is are currently highly useful second-line agents in patients with total statin intolerance This is a provisional file, not the final typeset article and in the near future, after expiration of patent protection, will be useful first line agents for hyperlipidemia.
Keywords: Atherosclerosis, Hyperlipidemia, LDL cholesterol, Lipid lowering agent, PCSK9 inhibitors, Statins
Received: 21 Dec 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Kyan, Gornbein and Saver. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Katie Kyan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.