The findings of LipidSnapshot indicate that the majority of ASCVD patients were not treated adequately, regardless of the treatment setting, age, or gender. However, some relevant health care differences were noted.

Primarily, the discrepancies in LLT and LDL-C levels among patients documented by both OBCs and GPs highlight a significant structural gap in the treatment landscape of ASCVD patients in Germany. Patients documented by GPs exhibited higher LDL-C levels, including a larger proportion of patients with LDL-C levels ≥ 190 mg/dL, which are indicative of a familial hypercholesterolemia (FH). Due to the immense cardiovascular risk associated with FH, these patients should undergo genetic testing and should be appropriately managed to achieve significant LDL-C reduction [6]. Furthermore, a lower proportion of patients in the GP cohort reached the LDL-C target levels of < 55 mg/dL, as compared to those documented by OBCs. A similar discrepancy is observed regarding the achievement rates for an LDL-C target of < 70 mg/dL. Therapy intensification, including combination therapy, is more prevalent in the OBC setting.

Regarding the discrepancies in target achievement rates between OBCs and GPs, it is essential to consider that disparate targets are applicable to these settings. While the ESC/EAS guidelines [6]. which are relevant for OBCs, recommend LDL-C reduction of ≥ 50% from baseline and a LDL-C target level of < 55 mg/dL in ASCVD patients, the NVL [5]. which is one of the main guidelines for GPs, mentions both the “fire-and-forget” strategy as well as the “treat-to-target” strategy with a target LDL-C level of 70 mg/dL. The attainment rates for the targets specified within the context of each setting are comparable between OBCs (< 55 mg/dL: 27.4%) and GPs (< 70 mg/dL: 28.7%), suggesting the discrepancies in LDL-C target attainment are mainly due to the divergent recommendations in the guidelines.

In addition to these discrepancies in guideline recommendations, current reimbursement restrictions for PCSK9 modifying therapies may contribute to discrepancies between OBCs and GPs. The current findings indicate that only a small number of patients are treated with PCSK9 modifying therapies, almost none of which were observed in the GP setting. In Germany, these therapies 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 permissible in the GP setting. The low prescription rates observed in the GP setting suggest that patients who consult an OBC tend to remain in specialist care.

It is unfortunate that treatment options, including the prescription of PCSK9i, are not being utilized to their fullest potential, given the effectiveness of these options. A simulation study indicated that approximately half of patients in secondary prevention require PCSK9i to achieve target LDL-C levels [7]. In the “Jena auf Ziel” study, high-risk ASCVD patients received a high-intensity statin in combination with ezetimibe. Among these patients, 80% achieved the LDL-C target levels recommended by the ESC/EAS. Only 20% of the patients required escalation therapy with bempedoic acid or PCSK9i. In all patients receiving triple therapy the LDL-C target was achieved [8].

Overall, the discrepancies observed between the OBC and the GP setting prompt the question of whether comparable LDL-C targets and treatment strategies across the various guidelines would be beneficial, given that the same patients are involved irrespective of the structural settings. Enhanced cross-sectional networking could also potentially improve patient care.

Secondly, the present findings indicate age-specific disparities. Most strikingly, approximately 50% of patients younger than 50 years who were treated in a GP setting had not received any treatment despite their elevated cardiovascular risk. The majority of patients in both the OBC and GP settings have not achieved the target level of < 55 mg/dL. These findings are analogous to those observed in a cross-sectional study conducted at a Danish hospital among patients who experienced a cardiovascular event before the age of 40 years. In the hospital setting, approximately 60% of patients had not attained the ESC/EAS-recommended target level, which was defined as < 70 mg/dL at the time of the study [11]. It is notable that this cohort of young patients who experienced premature cardiac events, is at an elevated long-term risk. Although the relative one-year mortality risk does not appear to be age-dependent [13]. the longer remaining lifespan significantly elevates the absolute lifetime risk. Hereditary conditions such as FH or elevated Lp(a) levels frequently contribute to premature cardiovascular risk and complicate cardiovascular prevention [6]. Furthermore, it has to be kept in mind that the majority of patients with early ASCVD are engaged in paid employment. Cardiovascular re-events result in either temporary or permanent inability to work, which can also have economic consequences and result in costs to the healthcare and social system [14].

In addition, our data indicates that older patients were more likely to receive a statin monotherapy in both settings compared to younger patients. On the other hand, the proportion of patients who remained untreated increases once more in the group of patients aged ≥ 80 years. These findings align with those of a Swedish and a Canadian cross-sectional study, which both reported lower rates of LLT among patients aged ≥ 85 years compared to patients aged 75 to 84 years [15, 16]. The lower treatment rate in elderly patients may be attributed to concerns about adverse effects and drug interactions in a multimorbid population [17]. Additionally, the risk of a subsequent cardiovascular event within the remaining life expectancy may be considered less significant, leading to a less favourable benefit-risk balance [18].

Thirdly, gender appears to influence lipid management in patients with ASCVD. In both treatment settings, LDL-C levels in men were observed to be numerically lower than in women, LDL-C levels indicative for FH were less common in men, and men were more likely to receive lipid-lowering treatment than women, indicating the presence of structural gender-related treatment differences.

These results are consistent with those of the EUROASPIRE IV cross-sectional study, initiated by the ESC. It was found that women were significantly less likely to achieve the LDL-C target than men and less likely to receive LLT. This was observed to be consistent across countries [12]. The EUROASPIRE study additionally indicates that the largest gender disparity was observed in patients with lower levels of education and advanced age. With advancing age and greater educational attainment, the gender gap diminished [19].

Previous research has indicated that lower adherence may be a potential explanation for the higher target failure rate observed in women [20]. Accordingly, a meta-analysis encompassing over 1.8 million elderly patients receiving statin treatment revealed that female gender was associated with nonadherence. The authors postulated that this may be attributable to heightened concerns about adverse effects among women or lower motivation to adhere to treatment due to underestimation of their cardiovascular risk [20]. As women overall tend to show greater concern for their health and engage more frequently with the health system than men [21]. the implementation of appropriate patient education may prove an effective means of reducing the gender gap.

Lp(a) was infrequently assessed, but more frequently in the OBC setting than in the GP setting and more frequently in patients receiving PCSK9i or non-statin LLT monotherapy. No discernible differences were identified based on age or gender, except for a slight tendency towards increased testing in younger patients. The ESC/EAS guidelines recommend Lp(a) testing, particularly in cases of premature ASCVD (Class IIa recommendation) [6]. In contrast, the NVL does not endorse Lp(a) testing [5]. which may explain the lower rates in the GP setting. However, although the ESC/EAS guidelines recommend measuring Lp(a) levels for each individual patient, this is not done as a standard procedure, even in younger patients in the OBC setting.

The present results are consistent with an analysis of claims data showing an Lp(a) testing rate of less than 2% even in younger patients with ASCVD [22]. A recent registry of cardiovascular rehabilitation clinics showed that Lp(a) is tested infrequently even in the context of major cardiac events, and at the same time the study demonstrated the above average prevalence of elevated Lp(a) levels in these patients [23]. The EAS/ESC Consensus Group has defined 50 mg/dL as relevant threshold for elevated Lp(a) levels [4]. According to the Copenhagen Heart Study, the prevalence of elevated Lp(a) levels above 50 mg/dL in the general European population is 20% [24]. In a cohort of 52,898 patients (not limited to patients with major cardiac events) admitted to a clinic for cardiology in Germany, 18.4% were reported to have Lp(a) levels above 50 mg/dL [25]. In our cohorts, the prevalence of elevated Lp(a) levels above 50 mg/dL is 26.8% in the OBC setting and 36.9% in the GP setting, higher in both settings than in the general population and in a cardiologic patient population not limited to those with major cardiac events.

In addition, the data revealed that the proportion of patients with levels below 30 mg/dL tended to be higher in the OBC cohort than in the GP cohort. The Lp(a) testing pattern suggests that OBCs and GPs may initiate Lp(a) testing in patients with different profiles. A lower overall prevalence of patients with Lp(a) levels below 30 mg/dL may be the result of a targeted approach to Lp(a) testing in the GP cohort. This focus is understandable as far as Lp(a) may be considered as a causal driver of ASCVD in patients with less remarkable elevation of LDL-C levels, patients with particularly early onset of ASCVD, or patients with recurrent events. Nevertheless, such a targeted approach may underestimate the Lp(a)-mediated risk in patients with a classic risk profile.

In order to accurately interpret the findings of the present study, it is essential to acknowledge the inherent limitations of the research design. It should be noted that the data were derived from disparate study parts, a prospective non-interventional study for OBC data and a retrospective analysis for GP data. The sample sizes between the two study parts differ considerably and the prospective OBC cohort is restricted to a sample size of 1,500 patients. This results in a relatively small number of subjects in some subgroups. Moreover, it should be noted that only 3.0% of the GPs and 20.3% of the OBCs within the panel provided Lp(a) levels. Missing data was not imputed. This lack of completeness in the Lp(a) data represents an additional limitation. In conclusion, the results can only be presented in a descriptive manner, and any interpretation should be regarded as hypothesis-generating.