“Jena auf Ziel” has demonstrated that stringent ESC/EAS LDL-C target attainment by early combination of a high-intensity statin with the cholesterol absorption inhibitor ezetimibe and escalation with bempedoic acid and PSCK9-I in patients with ST-elevation myocardial infarction (STEMI) is feasible, effective, and safe over a follow-up period of 12 months. The 2-year follow-up results presented in this analysis, however, are sobering as a substantial proportion of patients have failed to stay on ESC/EAS LDL-C targets 2 years after the index event. Patients managed in the outpatient lipid clinic of the University Hospital Jena had significantly better LDL-C goal attainment over time compared to patients treated by their local GPs. “Deprescribing” of previously implemented LLT was the main reason for LDL-C target failure after 24 months and was associated with higher LDL-C levels and major adverse cardiovascular events (MACEs).

The results of the current analysis highlight a significant structural gap in the treatment landscape of high-risk ASCVD patients in Germany.

Regarding the discrepancies in target achievement rates between the outpatient clinic of the University hospital in Jena and treatment by local GPs, it is essential to consider that disparate targets are applicable to these settings. While the ESC/EAS guidelines [5], which are relevant for cardiologist, recommend LDL-C reduction of ≥ 50% from baseline and a LDL-C target of < 55 mg/dL in very high-risk patients, the Nationale Versorgunsleitline (NVL) [13], which is followed by most GPs, recommends a “fire and forget” strategy and less aggressive lipid lowering with higher LDL-C targets (70 mg/dL).

In addition to discrepancies in guideline recommendations, current reimbursement restrictions for PCSK9 modifying therapies in Germany may contribute to these divergent results. The current findings indicate that bempedoic acid (BA) as well as PSCK9-I, which were initiated during the first 12 months of follow-up in the outpatient lipid clinic of the Jena University Hospital, were “deprescribed” in the GP setting during the second year of follow-up. In Germany, PCSK9-I must be initiated by specialists, including those in the fields of cardiology, nephrology, endocrinology, diabetology, and angiology, as well as by specialists in lipid outpatient clinics. Subsequently, a continuous prescription is also feasible in the GP setting, but, due to possible financial restrictions, is often not translated in daily clinical practice.

It is unfortunate that treatment options that are not generically available, such as BA and PCSK9-I, are not being utilized to their fullest potential, given the effectiveness of these options [8, 9]. Moreover, it is concerning that in high-risk patients after myocardial infarction, well-tolerated drugs are deprescribed without medical indications which leads to higher LDL-C levels and, most importantly, higher incidence of MACE.

The discrepancies observed earlier in LipidSnaphot and the current analysis of the “Jena auf Ziel” cohort between the OBC and the GP setting prompt the question of whether the NVL guidelines should be updated to meet best practice standards with more stringent LDL targets. This is all the more important since most patients with elevated levels of cholesterol are treated by GPs and not by cardiologists [15]. Therefore, enhanced cross-sectional networking could potentially improve patient care. Given the efficacy of available LLT, the rates of target achievement and adherence in clinical practice are concerning.

Our results parallel findings from the multinational SANTORINI study, which reported that only 20.1% of high- and very high-risk patients achieved guideline-recommended LDL-C levels in Europe, largely due to underutilization of combination LLT and inconsistent adherence to guidelines [8]. Koenig and colleagues reported only recently a retrospective analysis from German claims data that there are high discontinuation rates of LLT, with statins having the lowest long-term persistence [16]. These findings underscore the challenges of long-term adherence to LLT and the need for improved strategies to optimize LDL-C control [17].

Our study identified a significant association between LDL-C levels and MACE incidence, with patients experiencing MACE having higher LDL-C levels and shorter durations at target LDL-C. This aligns with recent findings from SWEDEHEART, which demonstrated that patients with sustained reductions in non-HDL-C had the lowest risk of MACE [10, 12]. The importance of sustained LDL-C reduction is further supported by evidence indicating that higher LDL-C exposure over time contributes to atherosclerotic cardiovascular disease [18].

Our findings reinforce the necessity for systematic approaches to LDL-C management, including standardized treatment algorithms and improved adherence strategies. Given that “deprescribing” by GPs was a significant barrier to LDL-C goal attainment over time, targeted education and guideline reinforcement for primary care providers may be beneficial. Moreover, the result of the current analysis are a clear call to guideline harmonization in Germany. Differing treatment algorithms and LDL-C target recommendations by medical societies is a major driver for confusion. Furthermore, expanding access to lipid clinics and utilizing telemedicine-based interventions could improve long-term adherence to LLT. Future research should explore the implementation of structured LDL-C management programs and assess their impact on long-term cardiovascular outcomes.