Nationwide LDL-C goal attainment in high-risk and very-high-risk patients in Denmark: real-world lipid management and simulated impact of guideline implementation.
LDL-C goal attainment remains suboptimal in Denmark, but simulated optimal implementation of lipid-lowering therapy guidelines could substantially improve attainment, prevent hundreds of annual cardiovascular events, and generate meaningful healthcare cost savings.
Key Findings
Results
Real-world LDL-C goal attainment at follow-up was low across all patient groups, particularly in secondary prevention.
Among 487,962 individuals (336,705 primary prevention and 151,257 secondary prevention), follow-up LDL-C goal attainment in primary prevention was 39.8% under the Danish guideline and 15.1% under the European guideline.
In secondary prevention, goal attainment was 18.8% under both guidelines.
Data were drawn from a nationwide registry-based cohort study using LDL-C measurements between January 2022 and December 2023, with repeat measurements 6–15 months later.
Patients were aged 30–85 years and classified as high-risk or very-high-risk for ASCVD.
Results
Simulated optimal implementation of lipid-lowering therapy substantially increased LDL-C goal attainment under both guidelines.
Under the Danish guideline, optimal implementation increased attainment to 91.9% in primary prevention and 63.5% in secondary prevention.
Under the European guideline, optimal implementation increased attainment to 75.8% in primary prevention and 96.8% in secondary prevention.
The simulation modeled stepwise intensification of therapy including statins, ezetimibe, and PCSK9 inhibitors within current Danish reimbursement restrictions.
The large gap between real-world and simulated attainment indicates substantial undertreatment in current clinical practice.
Results
Implementation of the Danish guideline could prevent hundreds of cardiovascular events annually compared with real-world outcomes.
Compared with real-world outcomes, Danish guideline implementation could annually prevent 589 strokes, 491 myocardial infarctions, 581 revascularisations, and 196 cardiovascular deaths.
These estimates were derived from the simulation model applied to the nationwide cohort of high-risk and very-high-risk patients.
The preventable event estimates reflect the clinical impact of closing the gap between current and optimal lipid-lowering therapy use.
Results
Implementing the European guideline instead of the Danish guideline would avert additional cardiovascular events and generate greater cost savings.
The European guideline would avert an additional 179 strokes, 156 myocardial infarctions, 166 revascularisations, and 67 cardiovascular deaths annually compared with the Danish guideline.
This difference corresponds to annual clinical event cost savings of €15.8 million.
The Danish and European guidelines differ in LDL-C goal thresholds, treatment recommendations, and access to advanced lipid-lowering therapy.
The European guideline has stricter LDL-C targets, particularly for very-high-risk patients, which drives additional event prevention.
Methods
The study identified a large nationwide cohort of high-risk and very-high-risk ASCVD patients with repeated LDL-C measurements in Denmark.
The cohort included 487,962 individuals: 336,705 classified as primary prevention and 151,257 as secondary prevention.
All patients had LDL-C measurements between January 2022 and December 2023 and a repeat measurement 6–15 months later.
The study used a nationwide registry-based design, capturing real-world lipid management across Denmark.
Eligible patients were aged 30–85 years and classified as high-risk or very-high-risk for ASCVD.
Discussion
Early and broader adoption of combination lipid-lowering therapy, including PCSK9 inhibitors, was identified as key to improving LDL-C goal attainment.
The simulation modeled stepwise intensification including statins, ezetimibe, and PCSK9 inhibitors.
Current Danish reimbursement restrictions on PCSK9 inhibitors limit access and contribute to the gap between real-world and optimal attainment.
The authors concluded that 'early and broader adoption of combination lipid-lowering therapy could substantially improve LDL-C goal attainment, reduce cardiovascular events and generate meaningful healthcare cost savings.'
Secondary prevention patients had particularly low real-world attainment (18.8%) despite being the highest-risk group, suggesting a critical treatment gap.
What This Means
This research analyzed cholesterol management across nearly 488,000 Danish adults who are at high or very high risk of heart disease or stroke. Researchers looked at whether these patients had their 'bad' (LDL) cholesterol reduced to recommended target levels, and then used a computer model to estimate how many heart attacks, strokes, and deaths could be prevented if doctors followed cholesterol treatment guidelines more closely. The study found that current real-world treatment is falling far short: only about 19% of patients who already have heart disease reached their cholesterol target, and primary prevention patients fared only moderately better. This suggests that a large proportion of high-risk patients are not receiving adequate cholesterol-lowering treatment.
When the researchers simulated what would happen if guidelines were fully implemented — using a step-by-step approach of statins, then adding ezetimibe, then adding newer powerful drugs called PCSK9 inhibitors — goal attainment improved dramatically. Following Danish guidelines optimally could prevent nearly 600 strokes, about 500 heart attacks, and almost 200 cardiovascular deaths every year in Denmark alone. Switching to the stricter European guidelines, which set lower cholesterol targets especially for the highest-risk patients, would prevent even more events and save an additional €15.8 million annually in healthcare costs.
This research suggests that there is a major missed opportunity in cardiovascular disease prevention in Denmark, and likely in similar countries, due to undertreating high-risk patients with available cholesterol-lowering medications. The findings point to the potential value of broader access to combination therapies — including newer, more potent cholesterol-lowering drugs — and closer adherence to evidence-based treatment guidelines as strategies to reduce the burden of heart disease and stroke at a population level.
Mohamed A, Rached R, Kantsø L, Honore E, Lauridsen B, Fijolek A, et al.. (2026). Nationwide LDL-C goal attainment in high-risk and very-high-risk patients in Denmark: real-world lipid management and simulated impact of guideline implementation.. Open heart. https://doi.org/10.1136/openhrt-2026-004265