Suboptimal management of hypercholesterolemia in countries with high or very high cardiovascular risk: findings from the international DISCOVERY study

Abstract

Introduction: The 2019 ESC/EAS guidelines introduced stricter low-density lipoprotein cholesterol (LDL-C) targets, particularly for patients at high and very high cardiovascular (CV) risk. However, data on the implementation of these targets in real-world clinical practice-especially in countries with high/very high CV risk-remain limited. The DISCOVERY study aimed to assess LDL-C management, lipid-lowering therapy (LLT) use, and guideline adherence across multiple countries in Central and Eastern Europe and Central Asia.

Methods: This prospective, observational, multicenter study enrolled adult patients with hypercholesterolemia (HCL) from 10 countries grouped into three regions. Data was collected at baseline and after 12 weeks of follow-up. LLT patterns, LDL-C levels, target attainment (both investigator-defined and 2019 ESC/EAS-recommended), and physician adherence to guidelines were analyzed.

Results: A total of 6,447 patients were included; 53.2% were female, and the mean age was 60.5 ± 11.9 years. Most patients (66%) were in secondary prevention. At baseline, 36.8% had been treated with LLT. After the first visit, treatment was changed in 78% of patients, but only 42.4% received high-intensity statins and 9.3% received statin-ezetimibe combinations at follow-up. LDL-C target achievement was poor: only 5.6% of patients met the guideline-recommended LDL-C goals, compared to 45.5% who met physician-defined targets. Among patients with ASCVD, only 3.3% achieved guideline LDL-C targets. The most significant gap was observed between guideline recommendations and physician-set LDL-C goals. No significant difference in LDL-C target attainment was observed between specialists and general practitioners.

Discussion: The DISCOVERY study reveals suboptimal LDL-C control and low adherence to the 2019 ESC/EAS guidelines in routine practice across countries with high/very high CV risk. These findings highlight the urgent need for strategies to improve physician awareness, promote intensive LLT use, and close the gap between guidelines and clinical practice. A paradigm shift toward proactive LDL-C management is essential to reduce residual CV risk in these populations.

Keywords: ESC/EAS guidelines; LDL-C; cardiovascular risk; ezetimibe; hypercholesterolemia; lipid-lowering therapy; real-world evidence; statins.

Figure 1

Distribution of concomitant diseases overall and by region. R, region; RF, risk factor; CV, cardiovascular.

Figure 2

Comparison between the achievement of target LDL-C levels by investigator and by 2019 ESC/EAS guidelines (overall and by category of individuals) at 2nd visit. HCL, hypercholesterolemia; LDL-C, LDL cholesterol; LLT, lipid-lowering therapy; ESC/EAS, European Society of Cardiology/European Atherosclerosis Society; DM, diabetes mellitus. * Percentages with respect to those patients with HCL diagnosis and on LLT who had both LDL-C level record at 2nd visit and the record of the investigator-determined LDL-C target level. ** Percentages with respect to those HCL patients on LLT who had records of LDL-C level at 2nd visit and for whom it was possible to determine their target LDL-C according to the ESC/EAS guidelines.

Figure 3

Comparison between regions and countries in terms of LDL-C lowering (1st and 2nd visits) and in terms of the achievement of LDL-C target recommended by 2019 ESC/EAS guidelines at 2nd visit among secondary prevention patients. LDL-C, LDL cholesterol; ESC/EAS, European Society of Cardiology/European Atherosclerosis Society; R, region; HU, Hungary; SI, Slovenia; BA, Bosnia and Herzegovina; BG, Bulgaria; KO, Kosovo; NMK, North Macedonia; RO, Romania; MD, Moldova; MN, Mongolia; UZ, Uzbekistan.

Figure 4

Modified version of the continuing LLT from 1st to 2nd visit overall and by region, adapted from Šabović et al. (14). R, region; PCSK9, proprotein convertase subtilisin/kexin type 9; LLT, lipid-lowering therapy. * fenofibrate, ezetimibe, omega-3 products, red yeast rice products, simvastatin/fenofibrate, PCSK9 inhibitors, artichokes product, ciprofibrate.