Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: a population-based study

Giulia Corn; Marie Lund; Niklas W Andersson; Tine L Dohlmann; Mark A Hlatky; Jan Wohlfahrt; Mads Melbye

doi:10.1016/j.ahj.2024.04.018

Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: a population-based study

Am Heart J. 2024 May 4:S0002-8703(24)00105-4. doi: 10.1016/j.ahj.2024.04.018. Online ahead of print.

Authors

Giulia Corn¹, Marie Lund², Niklas W Andersson³, Tine L Dohlmann³, Mark A Hlatky⁴, Jan Wohlfahrt⁵, Mads Melbye⁶

Affiliations

¹ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.; Danish Cancer Institute, Statistics and Data Analysis, Copenhagen, Denmark. Electronic address: gico@ssi.dk.
² Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.; Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
³ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
⁴ Department of Health Policy and Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.; Danish Cancer Institute, Cancer Epidemiology and Surveillance, Copenhagen, Denmark.
⁶ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Institute, Copenhagen, Denmark; K.G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Norway; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.

PMID: 38710378
DOI: 10.1016/j.ahj.2024.04.018

Abstract

Background: The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.

Methods: This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (p-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations.

Results: Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance.

Conclusion: Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.

Keywords: LDL-cholesterol; Pharmacoepidemiology; atorvastatin; cardiovascular prevention; simvastatin; statin response.