Trial reportJournal of lipid research2010
High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol.
Trial report in Journal of lipid research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06381947 (Efficacy and Safety of Bempedoic Acid in Association With Anti-PCSK9 and Ezetimibe in Statin-intolerant Patients), which is not on this map. Cited by 97 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy and Safety of Bempedoic Acid in Association With Anti-PCSK9 and Ezetimibe in Statin-intolerant Patients: a Randomized Crossover Trial
Who cites it
97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 244 citations in OpenAlex.
- Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- The Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review.Current cardiology reviews · 2017Pooled it
- Lipid-lowering efficacy of atorvastatin.The Cochrane database of systematic reviews · 2015 · on this mapPooled it
- PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.BMC medicine · 2022Trial
- Trial
- Pharmacokinetics and exploratory efficacy biomarkers of bococizumab, an anti-PCSK9 monoclonal antibody, in hypercholesterolemic Japanese subjects .International journal of clinical pharmacology and therapeutics · 2019Trial
- Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat-a randomized controlled dietary intervention study.The American journal of clinical nutrition · 2019Trial
- Effects of Hedan Tablet () on lipid profile, proprotein convertase subtilisin/kexin type 9 and high-density lipoprotein subfractions in patients with hyperlipidemia: A primary study.Chinese journal of integrative medicine · 2016Trial
- Short- and long-term effects of xuezhikang, an extract of cholestin, on serum proprotein convertase subtilisin/kexin type 9 levels.Chinese journal of integrative medicine · 2016Trial
- Ancestry and other genetic associations with plasma PCSK9 response to simvastatin.Pharmacogenetics and genomics · 2014Trial
- Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials.BMC cardiovascular disorders · 2014Trial
- Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies.Cardiovascular drugs and therapy · 2014Trial
- Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial.Lancet (London, England) · 2014Trial
- Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9.Clinical drug investigation · 2013Trial
- Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.PloS one · 2013Trial
- Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans.Journal of lipid research · 2010Trial
- Trial
- Octacosanol: A Natural Bioactive Ingredient for Atherosclerosis Prevention and Cardiovascular Health Promotion.Molecules (Basel, Switzerland) · 2026Review
- Relationship between lipoprotein(a) and PCSK9 in angiogram-proven premature coronary artery disease in an Asian cohort.Scientific reports · 2026Article
- Lower body mass index is associated with the achievement of target LDL in patients using PCSK9 inhibitors in Taiwan.European journal of medical research · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum LDL-cholesterol (LDL-C) levels. PCSK9 is secreted by the liver into the plasma and binds the hepatic LDL receptor (LDLR), causing its subsequent degradation. We first demonstrated that a moderate dose of atorvastatin (40 mg) increases PCSK9 serum levels, suggesting why increasing statin doses may have diminished efficacy with regard to further LDL-C lowering. Since that initial observation, at least two other groups have reported statin-induced PCSK9 increases. To date, no analysis of the effect of high-dose atorvastatin (80 mg) on PCSK9 over time has been conducted. Therefore, we studied the time course of atorvastatin (80 mg) in human subjects. We measured PCSK9 and lipid levels during a 2-week lead-in baseline period and every 4 weeks thereafter for 16 weeks. We observed that atorvastatin (80 mg) caused a rapid 47% increase in serum PCSK9 at 4 weeks that was sustained throughout 16 weeks of dosing. Importantly, while PCSK9 levels were highly correlated with total cholesterol (TC), LDL-C, and triglyceride (TG) levels at baseline, atorvastatin (80 mg) completely abolished all of these correlations. Together, these results further suggest an explanation for why increasing doses of statins fail to achieve proportional LDL-C lowering.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.