A landmark study spanning three continents and more than 1.1 million patients has revealed that people at high risk of a first heart attack or stroke are routinely left untreated, untested and off-target when it comes to their cholesterol, exposing one of the largest and most consistent gaps between cardiology guidelines and everyday clinical practice ever documented. The research, known as VESALIUS-REAL and published in Clinical Research in Cardiology, analysed real-world medical and pharmacy records from 11 databases across North America, Europe and the Asia-Pacific region between 2017 and 2022, and found that 60 percent of high-risk patients were not receiving any lipid-lowering therapy at all when they should have been.
The population studied is one that cardiologists consider a critical window of opportunity. These were patients aged 50 or older who had established atherosclerotic disease—coronary artery disease, atherosclerotic cerebrovascular disease or peripheral artery disease—or high-risk diabetes marked by microvascular complications or chronic insulin use. All had elevated atherogenic lipids, defined as low-density lipoprotein cholesterol (LDL-C) of at least 2.3 mmol/L (90 mg/dL), non-high-density lipoprotein cholesterol of at least 3.1 mmol/L (120 mg/dL), or apolipoprotein B of at least 0.8 g/L, together with additional cardiovascular risk factors such as chronic kidney disease stage 3 or 4, familial hypercholesterolaemia, early menopause, age 65 or older, or a history of tobacco use. Crucially, none had yet experienced a myocardial infarction or stroke, and none had end-stage renal disease. This cohort definition was deliberately aligned with the VESALIUS-CV randomised trial, which demonstrated that intensifying lipid lowering with the PCSK9 inhibitor evolocumab in exactly this kind of population reduced major cardiovascular events by 25 percent compared with standard therapy alone—a hazard ratio of 0.75 with a 95 percent confidence interval of 0.65 to 0.86.
Against that trial evidence, the real-world picture is stark. Of the 1,126,756 patients identified, 51 percent were female, and median LDL-C levels at the index date ranged from 2.4 mmol/L in Hong Kong to 3.4 mmol/L in Germany—levels at which guidelines from the European Society of Cardiology, the American Heart Association and their counterparts unequivocally recommend treatment. Yet approximately 40 percent of patients overall were on lipid-lowering therapy at index, with the highest uptake in Hong Kong at 61 percent. When treatment was present, it was overwhelmingly statin monotherapy, which accounted for between 74 and 97 percent of regimens depending on the country. Ezetimibe monotherapy rarely exceeded 3 percent, PCSK9-targeting agents as monotherapy were used in fewer than 1 percent of patients, and combination therapy ranged from just 1 percent in Hong Kong to 17 percent in Italy.
The therapeutic inertia persisted over time. Among the 830,516 patients with at least one year of follow-up, only 27 percent of those untreated at baseline initiated lipid-lowering therapy within the year. Initiation rates varied enormously—from 11 to 12 percent in Japan to 55 to 62 percent in Spain—but even in the best-performing systems, nearly half of clearly eligible patients went untreated. For those already on therapy, intensification was rarer still: only 9 percent had any increase in treatment intensity, whether through a higher statin dose, a switch to a more potent agent, or the addition of another drug class. Women fared worse on both counts, with 25 percent initiating therapy versus 29 percent of men, and 8 percent intensifying versus 11 percent. When intensification did occur, it typically meant stepping up from low- to moderate- or high-intensity statins; the addition of ezetimibe to high-intensity statins ranged from 1 percent in the United Kingdom to 9 percent in Sweden, and adding a PCSK9-targeting agent to statin therapy was generally below 1 percent.
Monitoring—the prerequisite for knowing whether treatment is working—was itself inconsistent. Overall, only 52 percent of patients had their LDL-C measured within a year of follow-up, with rates ranging from 23 percent in South Korea to 92 percent in Hong Kong, and testing was less frequent in women than men (50 versus 54 percent). Among the patients who did have a follow-up lipid measurement, just 21 percent achieved their locally guideline-recommended LDL-C goal, which was set at 1.8 mmol/L (70 mg/dL) for most regions in line with multi-society recommendations, and at 2.6 mmol/L (100 mg/dL) for the Japanese database in accordance with Japan Atherosclerosis Society and Japanese Circulation Society guidelines. Goal attainment was substantially better among patients on therapy at baseline (29 percent) than those without (15 percent), but remained strikingly low everywhere—and lower in women than men, at 18 versus 24 percent. In Germany, only 8 percent of women reached their target compared with 14 percent of men.
The sex disparities echo a growing body of evidence that women with equivalent or even higher LDL-C levels receive less aggressive lipid management. The authors note that the differences cannot be fully explained in an observational dataset, but point to prior literature suggesting that risk perception, treatment prioritisation and healthcare access all contribute. Notably, women in the cohort had a lower prevalence of coronary artery disease and high-risk diabetes but a higher prevalence of cerebrovascular and peripheral artery disease, and median LDL-C and non-HDL-C levels were actually higher in women than men across the databases—making the lower rates of combination therapy, testing and goal attainment all the more conspicuous.
Methodologically, the study’s strength lies in its harmonisation. Rather than pooling heterogeneous national statistics, the investigators applied a common protocol and a shared analytical data model across claims and electronic medical record databases including HealthVerity in the United States, the German Disease Analyzer, The Health Improvement Network in Italy and Spain, the PHARMO Data Network in the Netherlands, Swedish national and regional healthcare registries, CPRD Aurum in the United Kingdom, DeSC in Japan, the Hospital Authority database in Hong Kong, NHIS-HEALS in South Korea, and the Chang Gung Research Database in Taiwan. Lipid-lowering therapy was captured using WHO anatomical therapeutic chemical codes, and the index date was defined as the earliest point at which every inclusion criterion was met, with patients required to have at least two years of prior observability to exclude misclassification. The scale—over a million patients from three continents—makes this one of the largest real-world analyses of lipid management ever conducted, and the consistency of the findings across wildly different healthcare systems strengthens the conclusion that the treatment gap is systemic rather than local.
The authors caution that the cohort was restricted to patients with documented elevated lipids, so the results describe the subgroup with the clearest indication for further LDL-C lowering rather than all high-risk individuals. Routine data may also miss out-of-hospital care and over-the-counter medication, potentially underestimating true treatment use, and information on adherence and treatment duration was unavailable. Goal attainment was assessed only among patients with follow-up lipid measurements, a more selective and presumably better-monitored subgroup—meaning that goal achievement across the entire high-risk population is likely even lower than the headline 21 percent. The observational design also precludes determining why the gaps exist, though the authors point to a combination of clinical decision-making, patient factors such as adherence and statin intolerance, and healthcare system constraints including reimbursement and access, particularly for newer agents.
The biological rationale for closing these gaps is well established. Large epidemiological and genetic studies show that cumulative lifetime exposure to LDL-C is a key determinant of atherosclerotic burden, and that each sustained reduction in LDL-C lowers the risk of major adverse cardiovascular events in a dose- and time-dependent manner, with earlier intervention yielding greater long-term benefit. International guidelines accordingly recommend at least a 50 percent LDL-C reduction and a goal below 1.8 mmol/L for high-risk patients, and below 1.4 mmol/L (55 mg/dL) for groups such as those with coronary artery disease. The VESALIUS-CV trial’s demonstration that evolocumab added to optimised standard therapy prevented major events in a pre-event population reinforces the point that proactive, early intensification—rather than waiting for a first infarct—is both feasible and effective.
The study’s conclusion is blunt: despite the widespread availability of effective therapies and well-established guidelines, most high-risk patients remain untreated or undertreated and fail to meet recommended targets, and only about half are even monitored. The authors argue that addressing this will require multifaceted strategies—improving LDL-C testing rates, promoting earlier initiation of lipid-lowering therapy, making fuller and more timely use of combination regimens including statins, ezetimibe and PCSK9-targeting agents where guidelines support them, and tackling structural barriers of access, reimbursement and healthcare delivery. Because the data reflect practice between 2017 and 2022, the team calls for future studies to assess whether recent guideline updates and emerging evidence have begun to translate into better care. For now, the message from more than a million patient records is clear: the patients most likely to benefit from preventing their first cardiovascular catastrophe are precisely the ones the system is failing to reach.
Subject of Research: Real-world lipid-lowering therapy use, LDL-C monitoring and LDL-C goal attainment among patients at high cardiovascular risk without prior myocardial infarction or stroke, across 11 databases in North America, Europe and the Asia-Pacific region.
Subject of Research: Medicine
Article Title: Gaps in lipid management among high-risk patients without prior MI or stroke: the VESALIUS-REAL global study
Article References: Chan, Q., Cegla, J., Laufs, U., Cornel, J. H., De Ferrari, G. M., Hagström, E., Huang, H.-K., Lopez-Miranda, J., Avcil, S., Brooks, C., Cars, T., Chan, A. Y. L., Chui, C. S. L., Duxbury, M., Lai, E. C.-C., Neasham, D., Ochs, A., O’Kelly, J., da Silva Lima, G. P., … Wong, I. C. K. (2026). Gaps in lipid management among high-risk patients without prior MI or stroke: the VESALIUS-REAL global study. Clinical Research in Cardiology. https://doi.org/10.1007/s00392-026-03014-1
Image Credits: AI Generated
DOI: 10.1007/s00392-026-03014-1
Keywords: atherosclerotic cardiovascular disease, cardiovascular prevention, lipid-lowering therapy, LDL cholesterol, observational study, treatment gaps, VESALIUS-REAL, statins, PCSK9 inhibitors, guideline adherence, primary prevention, sex differences
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Ophelia Keating. (September 4, 2026). VESALIUS-REAL study reveals lipid treatment gaps in high-risk patients lacking prior cardiovascular events. Scienmag. https://scienmag.com/vesalius-real-study-reveals-lipid-treatment-gaps-in-high-risk-patients-lacking-prior-cardiovascular-events/
Ophelia Keating. “VESALIUS-REAL study reveals lipid treatment gaps in high-risk patients lacking prior cardiovascular events.” Scienmag, 4 September 2026, https://scienmag.com/vesalius-real-study-reveals-lipid-treatment-gaps-in-high-risk-patients-lacking-prior-cardiovascular-events/. Accessed 4 September 2026.
Ophelia Keating. “VESALIUS-REAL study reveals lipid treatment gaps in high-risk patients lacking prior cardiovascular events.” Scienmag. September 4, 2026. https://scienmag.com/vesalius-real-study-reveals-lipid-treatment-gaps-in-high-risk-patients-lacking-prior-cardiovascular-events/
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