Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy

BackgroundGuidelines for dyslipidemia management recommend adding ezetimibe for patients with dyslipidemia inadequately controlled with statin monotherapy. A fixed-dose combination (FDC) of statin and ezetimibe may improve persistence and adherence and hence reduce LDL-C further compared to free-com...

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Main Authors: Mihail Samnaliev, Irfan Khan, Praveen Potukuchi, Kelly Lee, Genevieve Garon, Charlie Nicholls
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1461416/full
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author Mihail Samnaliev
Irfan Khan
Praveen Potukuchi
Kelly Lee
Genevieve Garon
Charlie Nicholls
author_facet Mihail Samnaliev
Irfan Khan
Praveen Potukuchi
Kelly Lee
Genevieve Garon
Charlie Nicholls
author_sort Mihail Samnaliev
collection DOAJ
description BackgroundGuidelines for dyslipidemia management recommend adding ezetimibe for patients with dyslipidemia inadequately controlled with statin monotherapy. A fixed-dose combination (FDC) of statin and ezetimibe may improve persistence and adherence and hence reduce LDL-C further compared to free-combination treatment (FCT). The primary aim was to compare persistence/adherence with FDC versus FCT of rosuvastatin and ezetimibe (R/E); the secondary aim was to assess the impact of treatment adherence and persistence to LDL-C percentage reduction from baseline. An exploratory analysis assessed the impact of treatment adherence and persistence to incidence of major adverse cardiovascular events (MACEs). A subgroup analysis of patients on FDC of rosuvastatin 10 mg and ezetimibe 10 mg was also conducted.MethodsA retrospective analysis was performed using the THIN® database from Belgium and France in individuals (aged ≥18 years who received R/E as FDC or FCT between January 01, 2017, and November 30, 2022). Persistence (time from landmark date to discontinuation, with the latter defined as >45 days gap between prescription fills) and adherence (having a proportion of days covered ≥80%) were defined. Subsequent analyses adopted propensity score matching or weighting, followed by Cox and logistic regression models.ResultsA total of 15,643 treatment episodes (FDC: 11,300; FCT: 4,343) were selected. FDC R/E was associated with greater persistence (HR: 0.54, 95% CI: 0.51–0.58) and higher odds of adherence (OR: 3.00, 95% CI: 2.70–3.30) than FCT R/E. Based on the regression analysis results, patients who were persistent to treatment had a 10% higher reduction in LDL-C values from baseline than those non persistent. Similarly, patients who were adherent had 9.6% higher reduction in LDL-C levels from baseline than those not adherent. No significant difference was observed in association between persistence/adherence and MACEs. A consistent trend was also observed in the subgroup analysis.ConclusionsIn conclusion, FDC of R/E use was associated with higher treatment persistence and adherence than FCT of R/E. Patients persistent/adherent to treatment had greater LDL-C reductions than those who discontinued or did not follow treatment schedule. The limited number of MACEs suggests a cautious interpretation of exploratory MACE findings.
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spelling doaj-art-b03d868b6b214e9fa0798bb4315dd3fe2025-08-20T02:30:35ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-05-011210.3389/fcvm.2025.14614161461416Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapyMihail Samnaliev0Irfan Khan1Praveen Potukuchi2Kelly Lee3Genevieve Garon4Charlie Nicholls5Department of RWE and HEOR Practice, Axtria, Boston, MA, United StatesDepartment of General Medicines Real World Evidence, Sanofi, Bridgewater, NJ, United StatesDepartment of General Medicines Real World Evidence, Sanofi, Bridgewater, NJ, United StatesDepartment of General Medicines and Market Access, Sanofi, Reading, United KingdomGlobal Medical Department of General Medicines, Sanofi, Toronto, ON, CanadaDepartment of General Medicines and Market Access, Sanofi, Reading, United KingdomBackgroundGuidelines for dyslipidemia management recommend adding ezetimibe for patients with dyslipidemia inadequately controlled with statin monotherapy. A fixed-dose combination (FDC) of statin and ezetimibe may improve persistence and adherence and hence reduce LDL-C further compared to free-combination treatment (FCT). The primary aim was to compare persistence/adherence with FDC versus FCT of rosuvastatin and ezetimibe (R/E); the secondary aim was to assess the impact of treatment adherence and persistence to LDL-C percentage reduction from baseline. An exploratory analysis assessed the impact of treatment adherence and persistence to incidence of major adverse cardiovascular events (MACEs). A subgroup analysis of patients on FDC of rosuvastatin 10 mg and ezetimibe 10 mg was also conducted.MethodsA retrospective analysis was performed using the THIN® database from Belgium and France in individuals (aged ≥18 years who received R/E as FDC or FCT between January 01, 2017, and November 30, 2022). Persistence (time from landmark date to discontinuation, with the latter defined as >45 days gap between prescription fills) and adherence (having a proportion of days covered ≥80%) were defined. Subsequent analyses adopted propensity score matching or weighting, followed by Cox and logistic regression models.ResultsA total of 15,643 treatment episodes (FDC: 11,300; FCT: 4,343) were selected. FDC R/E was associated with greater persistence (HR: 0.54, 95% CI: 0.51–0.58) and higher odds of adherence (OR: 3.00, 95% CI: 2.70–3.30) than FCT R/E. Based on the regression analysis results, patients who were persistent to treatment had a 10% higher reduction in LDL-C values from baseline than those non persistent. Similarly, patients who were adherent had 9.6% higher reduction in LDL-C levels from baseline than those not adherent. No significant difference was observed in association between persistence/adherence and MACEs. A consistent trend was also observed in the subgroup analysis.ConclusionsIn conclusion, FDC of R/E use was associated with higher treatment persistence and adherence than FCT of R/E. Patients persistent/adherent to treatment had greater LDL-C reductions than those who discontinued or did not follow treatment schedule. The limited number of MACEs suggests a cautious interpretation of exploratory MACE findings.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1461416/fullfixed-dose combinationfree-combination treatmentsingle-pill combinationpersistenceadherencemajor adverse cardiovascular events
spellingShingle Mihail Samnaliev
Irfan Khan
Praveen Potukuchi
Kelly Lee
Genevieve Garon
Charlie Nicholls
Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy
Frontiers in Cardiovascular Medicine
fixed-dose combination
free-combination treatment
single-pill combination
persistence
adherence
major adverse cardiovascular events
title Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy
title_full Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy
title_fullStr Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy
title_full_unstemmed Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy
title_short Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin–ezetimibe as a lipid-lowering therapy
title_sort treatment adherence persistence and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin ezetimibe as a lipid lowering therapy
topic fixed-dose combination
free-combination treatment
single-pill combination
persistence
adherence
major adverse cardiovascular events
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1461416/full
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