Association between adherence to statin therapy and low-density lipoprotein cholesterol (LDL-c) response in first-time users of standard-dose and low-dose statins: the PharmLines initiative

Abstract

Objective

To investigate whether statin adherence (defined as proportion days covered, PDC) is associated with LDL-c response in statin initiators on standard and low starting doses of statins, and to detect a possible interaction with sex.

Methods

An inception cohort study was conducted using the PharmLines Initiative, a linkage between the Lifelines Cohort Study and the University of Groningen’s IADB.nl (prescription database). First-time statin users were followed from baseline to follow-up measurement. We matched participants (1:1) between the standard-dose and the low-dose group of statin users on the duration of follow-up. Multiple linear regression analysis was used to model the association.

Results

In univariate analysis, PDC was significantly associated with LDL-c response similarly (slope = −0.021), in both the standard-dose group (N = 115, p < .001) and the low-dose group (N = 115, p = .003). In the standard-dose group, the same level of PDC appeared to be significantly associated with a greater LDL-c level reduction in women (slope = −0.027, N = 48, p < .001) than in men (slope = −0.017, N = 67, p < .001). Meanwhile, in the low-dose group, the reduction of LDL-c level from baseline seemed to be greater in men (slope = −0.023, N = 56, p < .001) than in women (slope = −0.020, N = 59, p < .001) for the same level of PDC. In multiple regression analysis, the significant association between PDC and LDL-c with a similar pattern to the univariate result was maintained only in the standard-dose group.

Conclusions

Adherence is significantly associated with LDL-c response to statins at follow-up. Sex appears to significantly modify this association. At a similar adherence level, women seem to experience a better LDL-c response to standard-dose statins compared to men in a real-world setting.

Keywords:

• Adherence
• statins
• low-density-lipoprotein cholesterol
• LDL-c

Transparency

Declaration of funding

The Lifelines Biobank initiative has been made possible by funds from FES (Fonds Economische Structuurversterking), SNN (Samenwerkingsverband Noord Nederland) and REP (Ruimtelijk Economisch Programma) and The IADB.nl is funded by the University of Groningen. The Indonesia Endowment Fund for Education (Lembaga Pengelola Dana Pendidikan, LPDP) of the Ministry of Finance of the Republic of Indonesia funded SI’s PhD program and had no role in all aspects of the study conduct or publication.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

EH and RAdB contributed to the conception or design of the work. SI drafted the manuscript. SDV and SI contributed to the statistical analysis of the data. JHJB prepared the data for the analysis. All authors contributed to the acquisition, analysis, or interpretation of the data. All authors critically revised the manuscript, gave final approval, and agreed to be accountable for all aspects of work ensuring integrity and accuracy.

Acknowledgements

The authors wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centres delivering data to Lifelines, and all the study participants, and the participating IADB.nl pharmacies for kindly providing their data for research.

Data availability statement

De-identified individual participant data that underlie the results reported in this study (text, tables, figures, appendices) can be made available upon request immediately following article publication for researchers whose proposed use of the data has been approved by an independent review committee (“learned intermediary”) identified for this purpose. The proposal should be directed to: [email protected].

Ethics approval

The Lifelines study protocol is approved by the medical ethical committee of the University Medical Center Groningen and all Lifelines participants have each signed an informed consent stating that he/she approves use of his/her (anonymized) data and material for scientific purposes. Data of the IADB.nl is collected according to the national and European guidelines on privacy with human data valid at the time of collection.

Consent to participate

Informed consent was obtained from all participants included in the study.