Background: Cardiovascular diseases (CVD) are the leading cause of death in Germany. Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major risk factor for CVD. A reduction in LDL-C levels by lipid-lowering therapy (LLT) is associated with a reduced risk of CVD. However, only a small proportion of patients achieve their risk-adapted LDL-C treatment goal. The effectiveness of LLT is impacted by patient`s persistence and adherence.

Objective: The aim of this project is to describe persistence and adherence to LLT in a real-world setting in Germany.

Methods: We performed a retrospective, longitudinal analysis of prescription data from the Insight HealthTM Patient Insights Tool. The database contains data from more than 62 million patients in Germany, covering approximately 77% of the outpatient statutory health insurance prescription market. Patients who were newly prescribed statins, ezetimibe or PCSK9-monoclonal antibodies [mAB] between July and December 2017 were included in the analysis and followed until March 2021. Persistence data were stratified by age and gender. Non-persistence was defined as LLT discontinuation with a prescription gap of ≥ 90 days between end of prescription duration and new prescription. Adherence to LLT was measured based on prescriptions as Proportion of Days Covered (PDC) in patients receiving at least two subsequent prescriptions.

Results: Pharmacy records from 865 732, 34 490 and 1 940 patients newly prescribed statins, ezetimibe and PCSK9-mAB were identified. After 12, 24 and 36 months, 39.2%, 26.6%, and 20.6% of patients remained on statin treatment, 39.7%, 28.1%, and 22.3% on ezetimibe and 69.4%, 60.1% and 50.9% on PCSK9-mAB (Figure 1). Persistence rates were lower in female patients compared to male patients across all regimens (Figure 2 to Figure 4). Persistence rates stratified by age are shown in Figure 5 to Figure 7. The mean PDC was 0.84, 0.92, 0.93 for statins, ezetimibe and PCSK9-mAB, respectively. The median treatment duration in patients who discontinued LLT was 133 days (25%;75%-quantile: 66; 350), 100 days (100; 329) and 239 days (84; 669) for statins, ezetimibe, and PCSK9-mAB, respectively. Most patients discontinued their LLT within 300 days after initiation (Figure 8). After discontinuation, most patients did not initiate any of the other LLT (Table 1). 

Conclusion: We found high rates of non-persistence across all LLT regimens, with a high proportion of patients not initiating another LLT after discontinuation, highlighting the need for improvements in LDL-C management. Further studies are needed to understand drivers of non-persistence in Germany.

Table 1 Subsequent therapy after treatment discontinuation

Initial treatment	Patients who discontinued treatment	Subsequent statin prescription %	Subsequent ezetimibe prescription %	Subsequent PCSK9-mAB prescription %	No subsequent LLT %	No subsequent therapy at all) %
Statins	402,991	-	1.4%	0.2%	79.2%	19.2%
Ezetimibe	19,723	33.1%	-	2.6%	55.8%	9.3%
PCSK9-mAB	735	26.1%	16.6%	-	53.1%	13.9%

Patients can receive more than one subsequent therapy.