High-intensity Statin Research Articles

Temporal trends in lipid management among Korean patients following acute myocardial infarction from 2011 to 2020

Abstract Background/Purpose Real-world data trends on dyslipidaemia prevalence and lipid management for patients following acute myocardial infarction (AMI) are lacking in South Korea, one of the Asia-Pacific nations. Our study aimed to evaluate the 10-year temporal trends of dyslipidaemia prevalence and lipid management in this patient population. Methods The study utilized datasets from two Korean AMI observational cohort (2011–2020) including a total of 26,751 participants (Figure 1A). The primary endpoints were as follows: (1) absolute low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dL; (2) relative LDL-C target of >50% LDL-C reduction from the baseline; (3) absolute or relative LDL-C target (American target); and (4) both absolute and relative LDL-C targets (European target). Results The prevalence of dyslipidaemia increased from 11.1% to 17.1% (Table 1, Figure 1B), while the statin prescription rates increased from 92.9% to 97.0% from 2011 to 2020. High-intensity statin use increased from 12.80% in 2012 to 69.30% in 2020 (Table 1) Interestingly, the yearlong substantial increases in the prescription rates of high-intensity statins were prominent between 2013 (21.9%) and 2014 (37.7%) and between 2018 (52.4%) and 2019 (66.1%), which may have been influenced by major revisions to the international lipid management guidelines and their adoption (Figure 1C). Ezetimibe use increased from 4.50% in 2016 to 22.50% in 2020. The achievement rate of the absolute and relative LDL-C targets increased from 41.4% and 20.8% in 2012 to 62.5% and 39.5% in 2019, respectively (Table 1). The achievement rates of the American (45.7% in 2012 to 68.6% in 2019) and European (16.5% in 2012 to 33.8% in 2019) targets showed similar increasing trends (Table 1, Figure 1D). Conclusions Despite the adoption of lipid management guidelines in clinical practice has improved, some patients some patients are unable to reduce their LDL-C concentrations to their target levels. Our real-world analyses emphasise the need for multidirectional and continued efforts to optimise lipid management and improve the clinical outcomes in these patients.Figure 1

Body mass index as a contributor to the accumulation of lipidic plaque materials in statin-treated type 2 diabetic patients with coronary artery disease: sub-analysis from the OPTIMAL randomized study

Abstract Background Patients with type 2 diabetes mellitus more likely exhibit obesity. Pathophysiologically, obesity promotes a range of metabolic disturbances including insulin resistance, dyslipidemia and hypertension, in addition to the secretion of adipokines and pro-inflammatory cytokines from excessive fat accumulation. These atherogenic features may promote instability of atherosclerotic plaques, which ultimately result in elevating a risk of atherosclerotic cardiovascular disease. However, it remains to be fully elucidated how obesity affects atherosclerotic plaque features in type 2 diabetic patients with coronary artery disease (CAD). Near-infrared spectroscopy (NIRS) imaging enables to quantitatively visualize lipidic plaque materials in vivo. This imaging modality provides insights into lipidic plaque features in obese patients with type 2 diabetes mellitus. Purpose To elucidate the association of body mass index (BMI, kg/m2) with lipidic plaque materials in type 2 diabetic patients. Methods The OPTIMAL study was a prospective randomized controlled trial to evaluate the efficacy of continuous glucose monitoring (CGM) guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic participants with CAD requiring PCI. 94 patients were randomized into CGM-guided or HbA1c-guided glycemic control. Serial NIRS imaging was conducted to monitor non-culprit lesions at baseline and week 48. The current sub-analysis included 78 patients with both baseline BMI data and evaluable baseline NIRS/IVUS images. Results All of study subjects received a statin (high-intensity statin use=36%), and the averaged LDL-C level was 86.7±26.3 mg/dL. The average BMI and HbA1c level were 24.7±3.1 kg/m2 and 7.5±0.9%, respectively (Table 1). On NIRS imaging analysis, maxLCBI4mm at non-culprit lesions was 286.2±167.0, and 21.8% of study subjects exhibited maxLCBI4mm >400 (Table 2). BMI was associated with maxLCBI4mm (p<0.001). Multivariate analysis adjusting clinical characteristics and LDL-C demonstrated that BMI was an independent contributor to maxLCBI4mm [estimate=17.15 (12.88-21.42), p<0.001] (Table 2). Even in patients receiving high-intensity statin, BMI was still associated with maxLCBI4mm (p<0.001). Conclusions A greater accumulation of lipidic plaque materials was observed in association with BMI in statin-treated type 2 diabetic patients with CAD. This presence of enhanced plaque vulnerability at non-culprit lesions, in the setting of obesity, may contribute to an increased risk of cardiovascular events in type 2 diabetic patients with CAD. The current finding suggests the need to adopt further therapeutic approaches to favourably modify plaque vulnerability in type 2 diabetic patients exhibiting obesity.Table 1:Clinical DemographicsTable 2:Factors Associated with maxLCBI

Relation of apolipoprotein C3 to risk of major adverse cardiovascular events and death after acute coronary syndrome on a background of optimized statin treatment

Abstract Background Apolipoprotein C3 (ApoC3), a component of triglyceride-rich lipoproteins and some low-density lipoprotein and high-density lipoprotein particles, has been shown to predict incident coronary heart disease (CHD) and major adverse cardiovascular events (MACE). However, it is unknown whether ApoC3 predicts risk in patients with acute coronary syndrome (ACS) receiving contemporary therapies including optimized statin treatment, and if any such association is independent of apolipoprotein B (ApoB) levels. Purpose We assessed the association of ApoC3 with first MACE (CHD death, nonfatal myocardial infarction, fatal or nonfatal ischaemic stroke, or hospitalization for unstable angina) and all-cause death in patients with recent ACS treated with high-intensity or maximum-tolerated statin and blinded PCSK9 inhibitor (alirocumab, ALI) or placebo (PBO). Methods ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months (M4; n=11,176) of treatment with ALI or PBO in the ODYSSEY OUTCOMES trial (which had 18,924 total participants). In continuous and spline analyses adjusted for treatment group and ApoB, we assessed the association of baseline ApoC3 with risk of MACE and death. In the ALI group we determined association of change in ApoC3 from baseline to M4 with risk of MACE and death after M4 in a model adjusted for baseline ApoC3 and ApoB, and the change in ApoB from baseline to M4. Results Median (Q1, Q3) baseline ApoC3 concentration was in a normal range [85 (65, 113) mg/L]. Continuous ApoC3 was not related to MACE (p=0.50) or death (p=0.51); spline analysis showed a slight curvilinear association of baseline ApoC3 with risk of MACE and death, but no clinically meaningful relationship (Figure). Findings were similar in the PBO group alone, and without adjustment for ApoB (data not shown). At M4, the median (Q1, Q3) change from baseline in ApoC3 was -10 (-27, -5; p<0.0001) mg/L with ALI and 2 (-14, 18; P = NS) mg/L with PBO. Overall, ALI significantly reduced the incidence of MACE (10.1% vs 12.1%; p=0.0006) and death (3.5% vs 4.2%; p=0.045) compared with PBO among those with available baseline ApoC3. However, the change in ApoC3 on treatment with ALI did not predict the risk of MACE or death after M4. Findings were qualitatively similar without adjustment for ApoB or its change. Conclusion In a cohort with recent ACS receiving optimized statin therapy and with median baseline ApoC3 in a normal range, ApoC3 did not provide clinically meaningful prediction of cardiovascular events or death. A modest reduction of ApoC3 by ALI did not associate with subsequent risk of MACE or death. It remains uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk.

Plasma levels of human growth differentiation factor 15 (GDF-15) and their effect of alirocumab on major adverse cardiovascular events and all-cause death after acute coronary syndrome

Abstract Background Human growth differentiation factor 15 (GDF-15) is a stress response cytokine of the transforming growth factor-β superfamily with roles in health and disease, cell survival and inflammation, and whose elevated plasma levels impair muscle metabolism and cause cachexia. GDF-15 also may play multiple roles in the pathophysiology of cardiovascular disease. Methods The ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab to placebo added to high-intensity or maximum-tolerated statin in patients post-acute coronary syndrome (ACS). We assessed in >11,000 patients for whom biobank samples were available, the relation between GDF-15 levels (Roche Diagnostics) at baseline and at 4 months with risk of major adverse cardiovascular events (MACE; primary endpoint, comprising coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischaemic stroke, unstable angina requiring hospitalization) and all-cause death, with adjustment for age and sex. Results Median GDF-15 (quartile [Q]1, Q3) at baseline was 1022 (755, 1465) pg/mL and was reduced by a placebo-adjusted median of 22 pg/mL with alirocumab (p=0.0009) at month 4. This lowering of GDF-15 by alirocumab may represent the first such report via pharmacotherapy. In the placebo group, baseline GDF-15 was significantly associated with risks of MACE (Figure Panel A) and death (Panel B). Relative risk reduction with alirocumab did not vary according to baseline GDF-15 levels for MACE (Panel C) and death (Panel D). Four-year MACE absolute risk reduction [ARR (95% CI)] with alirocumab at Q1 and Q3 of baseline GDF-15 was 2.0% (0.1%, 3.9%) and 2.6% (0.2%, 5.0%), respectively. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE (p=0.46) but was associated with death (p=0.0009), with greater reductions translating to lower risk. Conclusion In patients with recent ACS, GDF-15 is a strong predictor of both MACE and death. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE but was associated with death (p=0.0009), with greater ARR reductions translating to lower risk. Figure. Splines for baseline GDF-15 vs risk of MACE (Panel A; spline p<0.0001) or all-cause death (Panel B; spline p<00001) through 4 years in the placebo group; treatment hazard ratio for MACE (Panel C; spline p=0.52) and all-cause death (Panel D; spline p=0.78). All splines reflect adjustment for age and sexFigure

The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.

Abstract Background Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach. Purpose We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events. Methods A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI). Results A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p<0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p<0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p<0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients. Conclusion Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.

Residual risk post acute coronary syndroms after 1 year of cardiac rehabilitation. Can we improve it?

Abstract How much do we reduce residual risk with a cardiac rehabilitation program? What is left to do? Which would be the impact of a lower cholesterol threshold for the use of more potent lipid lowering drugs on residual risk? We explored these issues. Methods We retrospectively analyzed clinical and biochemical data from patients after 1 year of cardiac rehabilitation following an acute coronary event. Changes in residual risk of combined myocardial infarction, stroke and cardiovascular death, and its modification with optimization of treatment in patients with suboptimal lipid control, and with the use of PCSK9 inhibitors in those with a LDL-cholesterol over 70 mg/dl, were estimated using the SMART-REACH model calculator. Wilcoson and McNemar tests for paired-samples were used in the statistical análisis. Results 262 consecutive patients were included. Median age was 63.5 years, 80.5% men, 89.3% stented. Baseline use of high intensity statins was 90.8%. After 1 year, the use of Ezetimibe was doubled to 77.1%, empaglifozin to 26%, and PCSK inhibitors were used only in 5%, with a residual use of colchicine. Blood pressure and Cholesterol profile improved after 1 year, with no change in HbA1c. Absolute 10- years and life-long residual risk were reduced 4.8% (95%CI:3.6-5.9) and 6% (95%IC: 4.5-7.5) respectively (both p<0.001). LDL-cholesterol was >55 mg/dl with a suboptimal lipid lowering treatment in 29.8% of patients: an optimization to higher dose of rosuvastatin/atorvastatin plus ezetimibe would decrease absolute 10-years and life-long residual risk in 7.2% (95%CI: 4.9-9.4) and 9.9% (95%CI: 6.4-13.5%) respectively (both p<0.001). LDL-cholesterol remained > 70 mg/dl after higher dose of statin plus ezetimibe in 13.7% of patients: use of PCSK9 inhibitors in this group would reduce absolute 10-year and life-long residual risk in an additional 5.4% (95%CI:2.4-7,6;p=0,018) and 7% (95%CI: 3,8-10,1) compared to maximal dose of statins plus ezetimibe. Conclusions Cardiac rehabilitation programs reduce cardiac risk 1 year after an acute coronary event. Residual risk remain very high, and a significant proportion of patients do not reach recommended targets and optimal lipid lowering treatment. Optimization of lipid lowering drugs, and a lower LDL-cholesterol threshold for the use of PCSK9 inhibitors, would have a significant impact on residual risk.Changes in residual riskPCSK9-inhibitors in LDLchol >70 mg/dl

Clinical reality and challenges with familial hypercholesterolemia patients management. 2024 results from the Regional Center for Rare Diseases (RCRD) Registry in Poland

Abstract Background HeFH is one of the most prevalent genetic diseases significantly increasing the risk of CVD events and mortality. Despite new achievements with earlier diagnosis and new effective drugs, most of heFH patients do not achieve LDL-C goal and are still on residual CVD risk. Purpose We aimed to present the most recent data from the regional FH registry in Poland to show the challenges and reality of everyday clinical management with FH patients. Methods The registry is conducted at the RCRD in the 2nd largest, supraregional hospital in Poland. The main inclusion criteria were being phenotypically or genetically diagnosed with FH. Nonadherence was investigated based on detailed interview, monitoring the treatment’s effects and purchasing prescribed medications. For this analysis we investigated only adult FH patients from the registry. Due to small number of cases (n=5), patients treated with inclisiran were not included in this analysis. Results We included 142 consecutive heFH patients at mean age 45,8±14,9 years (min/max 18-75 years; 60% women). Mean BMI was 29.6±5.52 kg/m2, mean baseline TC was 282.9±80 mg/dl (the highest observed was 600 mg/dl), LDL-C 204.2±72.5 mg/dL (the highest observed -762 mg/dl), TG - 151.1±123.4 mg/dl, Lp(a) 37.6±41.5 mg/dl and HDL-C - 52.3±14.2 mg/dl. Most patients were diagnosed with LDLR (72%) or APOB (24%) mutations. High intensity statin therapy was used in 74.3% of patents, ezetimibe (mostly as a part of combination LLT) in 47.2%, and PCSK9 inhibitors in all those that met the reimbursement criteria – 25.6% of FH patients. Non-adherence to statin therapy and ezetimibe in the follow up of 2 years was 27%. In patients treated with statin therapy and ezetimibe mean achieved LDL-C was 153.6±82.82 mg/dl and on triple therapy - 64.5±43.73 mg/dl. Mean achieved LDL-C in the investigated population was 87.9±55.5 mg/dl. LDL-C goal was achieved in 39% of patients – in those treated with triple therapy with PCSK9 inhibitors it was 57.14%, and in those on statins and ezetimibe only 27.1%. Combination therapy of statins and ezetimibe did not significantly change baseline Lp(a) level (p=0.109), but when PCSK9 inhibitors were introduced the mean Lp(a) reduction by 34.2% (p=0.049) was observed. Based on the multivariable regression analysis, the following factors played the most important role for FH patients to be on LDL-C target: DLCN total score (OR 1.21, 95%CI: 1.04-1.40; p=0.013), DLCN category (10.39, 1.43-75.29; p=0.021), ezetimibe use (4.78, 1.15-19.92; p=0.031), and PCSK9 inhibitors use (4.56; 1.40-14.86; p=0.012). Conclusions FH patients in Poland are diagnosed definitely too late (45 years) and most of them are still not on LDL-C goal. Double and especially triple therapy significantly, even 5 times, increase the chance of achieving LDL-C goal, therefore PCSK9 inhibitors should be available for all FH patients, without the limitations existing currently e.g., within B101 drug program in Poland.

Safety and Efficacy of Moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis

Abstract Background Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide, poses an important healthcare challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. Purpose This meta-analysis seeks to assess the impact of moderate-intensity statin plus ezetimibe (MIS+EZT) versus high-intensity statin monotherapy (HIS) on LDL < 70mg/dl; Total Cholesterol; LDL; High Density Cholesterol (HDL) and triglycerides levels. Our goal is to synthesize the existing evidence and pinpoint areas that warrant further investigation. Methods A thorough literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. Results In the 13 included studies, involving 8,592 patients, of which 4,525 (52.67%) received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 12 to 219 weeks, with participant ages varying from 66 to 76.5 years in the MIS+EZT group and from 67 to 75.9 years in the HIS group. Analysis revealed significant MIS+EZT-associated with greater percentages in Low Density Lipoprotein (LDL) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78 ; 95% CI [0.32; 1.92]; p=0.584; I²=35%). Conclusions This meta-analysis underscores the effectiveness of MIS+EZT in enhancing significant clinical outcomes for ASCVD patients, as evidenced by improvements in a greater percentage of patients achieved the LDL <70 target, LDL, Total Cholesterol and Triglycerides levels . Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

Functional improvement of non-infarct related coronary artery stenosis by extensive LDL-C reduction with a PCSK9 antibody: the FITTER trial, microvascular function analysis

Abstract Background Atherosclerosis and microvascular dysfunction are closely linked. Moreover, impaired microvascular function is strongly associated with increased risk on major adverse cardiac events. In patients presenting with acute coronary syndrome (ACS), microvascular function is reduced. PCSK9-inhibitors have shown to reduce plaque burden and lipid load in epicardial vessels and might exhibit similar results on microvascular vessels, thereby improving microvascular function. The FITTER trial offers the unique opportunity to test this hypothesis. Methods The FITTER trial is a multi-center, randomized, double blind, placebo controlled clinical trial for patients presenting with ACS and multi-vessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) measurement of non-infarct related artery (non-IRA) lesions was performed. Patients with intermediate, non-critical lesions (FFR: 0.67-0.85) were included in this trial. For exploratory purpose, additional physiological assessment of the non-IRA included coronary flow reserve (CFR) and microvascular resistance index (IMR) measurements. Microvascular function was evaluated using a pressure- and temperature-sensitive guidewire and a bolus thermodilution method. Participants were randomized and treated for 12 weeks with either evolocumab or placebo in addition to high-intensity statin therapy. Staged reevaluation was done at 12 weeks. After repeated physiology testing, PCI was performed if deemed necessary. Pre-defined exploratory analysis includes the absolute and relative difference in change between CFR and IMR from baseline to follow up in the non-IRA. PCSK9 inhibition might result in a relatively larger increase of CFR and larger decrease of IMR. Results Between March 2020 and August 2023, a total of 150 patients were included in the trial. In 61 patients (88.5% male, age 65.3 ± 9.1 years, 23.0% STEMI, 70.5% non-STEMI, 6.6% UAP) successful baseline and follow-up measurements of microvascular function were performed. Complete results will be available at the beginning of March 2024. The primary- and secondary endpoints will be submitted for late-breaking clinical trials selection. The results of this abstract will include a per vessel analysis of coronary artery microvascular function. Conclusion The FITTER trial will provide new insights on the potential of extensive LDL-C reduction with a PCSK9 antibody on microvascular coronary artery function in patients presenting with ACS and MVD.

Inflammation and cholesterol associated residual cardiovascular risk and its dependence on chronic kidney disease in statin treated patients with coronary artery disease

Abstract Background/Aim In statin-treated patients with chronic coronary syndrome (CCS) there is uncertainty about the relative contribution of inflammation and dyslipidaemia to residual cardiovascular risk, particularly in the presence of chronic kidney disease. We thus aimed to evaluate high sensitive C-reactive protein (hsCRP) and low density lipoprotein-cholesterol (LDL-C) as predictors of future events in these patients, stratified by estimated glomerular filtration rate (eGFR). Methods We identified patients with CCS on stable statin treatment from a contemporary all-comers cohort recruited at a large tertiary care center in Germany. We excluded patients with active malignancy, infectious disease or in a post-operative state. Cox regression for major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction, stroke) and all-cause death was performed adjusting for age, sex, arterial hypertension, diabetes mellitus, active smoking, body mass index and change in the intensity of statin therapy at discharge, with log(hsCRP) or LDL-C as the exposure variables. Interaction with eGFR (< vs. ≥ 60 ml/min/1.73m²) was investigated. Results 937 patients with CCS (mean age 71.1 years, 78.7% male, median hsCRP 2.0 mg/L, median LDL-C 73.0 mg/dl, median eGFR 71.3 ml/min/1.73m²) were followed-up over 4 years, with 101 cases of MACE and 171 cases of all-cause death recorded. The hazard ratios (HR) for MACE per standard deviation (SD) increase were as follows: log(hsCRP) 1.08 (95% confidence interval (CI) 0.87, 1.34; p = 0.48), LDL-C 1.10 (95% CI 0.89, 1.35; p = 0.37). For all-cause death the HRs for log(hsCRP) and LDL-C were 1.60 (95% CI 1.36, 1.88; p <0.001) and 0.88 (95% CI 0.74, 1.04; p = 0.14), respectively. Kaplan-Meier curves stratifying the cohort by median values of LDL-C and hsCRP consistently demonstrated a significantly higher risk of death in the subgroups with elevated hsCRP (Figure 1). Contrastingly for LDL-C, levels below (vs. above) the median were associated with a higher mortality rate. This is in part a reflection of a higher prevalence of high-intensity statin therapy in this subgroup (21.0 vs. 14.2%, p = 0.0081), in turn a reflection of greater severity of coronary artery disease (history of myocardial infarction 43.9 vs. 31.9%, p <0.001). Further confounding by unadjusted for diseases with a catabolic metabolism is possible. Interaction analysis with eGFR revealed that log(hsCRP) was predictive of all-cause mortality both in the presence and absence of chronic kidney disease, whilst lower LDL-C values were found to be predictive only at eGFR <60 ml/min/1.73m² (Table 1). Conclusion Residual inflammation as measured by hsCRP predicts all-cause mortality in statin-treated patients with CCS in this contemporary all-comers cohort, both in the presence and absence of chronic kidney disease. The predictive utility of LDL-C is limited, likely due to confounding e.g. by the intensity of lipid lowering medication.Kaplan-Meier curves (all-cause death)Interaction analysis with eGFR

Gender-differences in Polyvascular disease: implications for lipid-lowering management and cardiovascular outcomes

Abstract Background Polyvascular disease (PolyVD) exhibits extensive atherosclerotic disease in multiple vascular beds. Despite lowering LDL-C with a statin, patients with PolyVD still present elevated risks of subsequent atherosclerotic cardiovascular events, suggesting the need to better understand pathophysiology of PolyVD. Female gender has been reported to mitigate severity of atherosclerotic disease and future events’ risks. However, whether this gender-difference exists in patients with PolyVD remains to be fully elucidated yet. Purpose To characterize gender-differences in cardiovascular outcomes in patients with and without PolyVD, respectively. Methods The on-going multi-center registry enroll patients with CAD receiving intravascular imaging-guided PCI. The current study included 679 patients with CAD. PolyVD was defined as the concomitance of other atherosclerotic cardiovascular disease (stroke and/or LEAD). In patients with PolyVD (n=185) and Non-PolyVD (n=494), clinical characteristics and major cardiovascular outcomes (MACE) were compared between men and women, respectively. MACE was defined as a composite of cardiovascular death, non-fatal MI, ischemic stroke, LEAD and coronary revascularization. Results The proportion of women was 21% and 18% in Non-PolyVD and PolyVD subjects, respectively. In patients with non-PolyVD, women were more likely to be older (75 vs. 68 years, p<0.001) and exhibit a lower BMI (22.3 vs. 24.0 kg/m2, p<0.001) with a lower frequency of previous myocardial infarction (13.5 vs. 24.9%, p=0.01). LDL-C levels did not differ between the two groups [102 (76-130) vs. 93 (71-120) mg/dL, p=0.06). However, during the observational period (median=3 years), women were associated with a lower frequency of MACE compared to men (HR=0.31, 95%CI=0.13-0.78, p=0.012, Figure, Table). In patients with PolyVD, BMI, and the frequency of established risk factors and previous myocardial infarction were comparable between men and women. Despite the use of high-intensity statin in over 40% of study subjects (44 vs. 36%, p=0.41), women still exhibited an elevated level of LDL-C [103 (74-122) vs. 82 (64-103) mg/dL, p=0.04]. Furthermore, in contrast to Non-PolyVD patients, similar cardiovascular outcomes were observed in both men and women with PolyVD (Figure). On multivariate analysis adjusting clinical characteristics, women were not a significant factor associated with a reduced risk of MACE (Table). Conclusion 18% of PolyVD were women who presented a higher LDL-C level. While women with Non-PolyVD exhibited better cardiovascular outcomes compared to men, this gender-difference did not exist in patients with PolyVD. Our findings indicate that female PolyVD did not necessarily show better outcomes but similar cardiovascular event’s risks compared to men. Further intensified anti-atherosclerotic managements are required in both men and women with PolyVD.

Efficacy of combination therapy with statin and ezetimibe versus high dose statin monotherapy in secondary prevention in high-risk patients

Abstract Background Secondary prevention in patients with acute coronary syndrome focuses on lowering low-density lipoprotein (LDL) cholesterol below 55 mg/dL. In all statin-naïve patients at high risk (LDL-cholesterol target <55 mg/dL), initiation of high-intensity statin monotherapy is recommended by ESC guidelines. Nonetheless, at one month, a significant proportion of patients do not reach their LDL-cholesterol target. Purpose The aim of this study was to compare lipid-lowering therapy with statin monotherapy versus statin with ezetimibe in secondary prevention in patients at high risk. Methods The current prospective study included 264 consecutive patients admitted with acute ST elevation myocardial infarction who underwent percutaneous coronary intervention. None of the patients had taken lipid-lowering drugs in the previous 12 months. Patients were randomly assigned to one of two treatment groups: Group 1 - rosuvastatin 40 mg (n= 144) and Group 2 - rosuvastatin 40 mg and ezetimibe 10 mg (n= 120). All patients' lipid profiles were assessed upon admission and after one month of lipid-lowering treatment. Results At baseline, no patient had LDL cholesterol level lower than 55 mg/dL. There was no significant difference in lipid profile at baseline between the two groups (all p > 0.05). No differences were observed between the two groups in terms of baseline LDL-cholesterol deviation from the target (103.4% versus 99.70%; p= 0.66). As expected, the combination therapy reduced LDL-cholesterol at one month significantly higher compared to high-dose statin monotherapy (-59.65% versus -37.54%; p< 0.0001). After one month of treatment, only 47.92% of patients in Group 1 reached the LDL-cholesterol target (<55 mg/dL) compared to 90.00% of the patients in Group 2 (p<0.0001; R.R.= 0.53). Conclusion(s) Our findings show that statin and ezetimibe combination therapy is more effective in reduction in LDL-cholesterol levels and reaching targets compared to statin monotherapy alone. In statin-naïve patients at high risk, early initiation of the statin and ezetimibe combination instead of statin monotherapy should be taken into account in secondary prevention, for an earlier reach of the LDL-cholesterol target and to reduce the overall cardiovascular risk.

Three decades of lipid-lowering therapy in type 2 diabetic patients with angiographically proven stable coronary artery disease

Abstract Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend<0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend<0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend<0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend<0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend<0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of <55 mg/dL (ptrend<0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

Serum lipid profiles and uptake of lipid-lowering therapy in patients with premature atherosclerotic cardiovascular disease (ASCVD) in comparison to older patients with ASCVD

Abstract Background Serum lipid levels are well-established risk factors for developing atherosclerotic cardiovascular disease (ASCVD). There are multiple guideline-supported treatments for managing dyslipidaemia for secondary prevention of ASCVD events. Lipid profiles and uptake of guideline-directed lipid-lowering therapy (GDLLT) is poorly characterised in patients with premature ASCVD compared to their older counterparts. Purpose To investigate serum lipid profiles and GDLLT uptake in patients with premature ASCVD in comparison to older patients with ASCVD. Methods Consecutive patients who underwent inpatient invasive coronary angiography at our institution between January 2019-December 2021 were examined. Patients with confirmed ASCVD on coronary angiography were stratified into two groups based on the 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias definition of premature ASCVD: Group 1 comprised of younger patients (<55 years for men, <60 years for women) and Group 2 comprised of older patients (≥55 years for men, ≥60 years for women). Demographics, clinical and biochemical parameters (including lipid profiles) and medications were obtained from the electronic medical record and compared between groups to identify differences in risk factor profiles. Results A total of 1437 patients (980 [68.2%] male, mean age 62.4±13.9 years) underwent coronary angiography. 916 patients (63.7%) had confirmed ASCVD, of which 225 were classified as premature ASCVD (24.6%, mean age 47.8±10.1 years) vs 691 older patients with ASCVD (75.4%, mean age 69.5±8.7 years). Group 1 patients had significantly higher mean BMI (31.7±8.1 vs 69.5±8.7; p=0.001) and lower prevalence of hypertension (54.2% vs 69.5%; p<0.001) or chronic kidney disease (5.3% vs 12.6%; p=0.002) compared to Group 2. There were no significant differences in sex, diabetes mellitus, or smoking history. Lipid profiles were significantly different between the two groups: Group 1 had higher levels of total cholesterol (TC), LDL-C, triglycerides, and TC/HDL-C ratio, but lower HDL-C levels (all p<0.001). A lower proportion of Group 1 patients were on GDLLT (42.7% vs. 60.3%; p<0.001). Amongst patients on GDLLT, there were similar rates in the use of high-intensity statins between groups, but Group 1 patients were significantly more likely to have an LDL-C level ≥1.8mmol/L (p=0.003). Multivariable models for individual lipid subfractions, accounting for gender, cardiovascular risk factors, and LLT use, showed that all lipid parameters remained significantly different between groups (all p<0.001). Conclusion Patients with premature ASCVD have significantly different lipid profiles compared to older ASCVD patients. They also have lower uptake of guideline-directed LLT and are less likely to meet recommended LDL-C targets for high-risk ASCVD despite therapy. These findings highlight the need for tailored risk factor evaluation and management in this population.

Effect of alirocumab on coronary plaque stratified by atherothrombotic risks

Abstract Background Previous clinical studies have shown that high-risk subgroups including patients with major atherosclerotic cardiovascular disease (ASCVD) events and multiple atherothrombotic risk factors derive enhanced cardiovascular benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. To date, the effect of alirocumab on coronary plaque regression stratified by the number of atherothrombotic risk factors remains unknown. Purpose To investigate the utility of atherothrombotic risk stratification to identify patients with acute myocardial infarction (AMI) who have the greatest potential for benefit on plaque regression as assessed by intracoronary imaging from the addition of alirocumab to high-intensity statin therapy. Methods This was a substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Intravascular ultrasound (IVUS) was serially performed in non-infarct-related coronary arteries at baseline and after 52 weeks. Atherothrombotic risk factors defined in the 2018 ACC/AHA cholesterol guidelines include myocardial infarction, ischemic stroke, peripheral artery disease, age ≥65 years, familial hypercholesterolemia, coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, LDL-C ≥100 mg/dL despite maximum tolerated statin therapy, and history of heart failure. The key endpoint was the change in IVUS-derived percent atheroma volume (PAV) from baseline to 52 weeks. Results A total of 263 patients available for serial IVUS data were analyzed for the current study. The most prevalent atherothrombotic risk factors were current smoking (49%), hypertension (43%), and age ≥65 years (24%). Patients were divided into 3 groups according to the number of risk factors (0 risk factor: n=52, 1 risk factor: n=101, ≥2 risk factors: n=100). Patients with risk factors had greater PAV at baseline compared with those with 0 risk factor (39.0% vs. 42.6% vs. 42.8%, P=0.008). The addition of Alirocumab to high-intensity statin therapy demonstrated a significant reduction in PAV among patients with 0 risk factor (-2.66% vs. -1.02%, P=0.009) and those with 1 risk factor (-2.36% vs. -0.76%, P<0.001) (Figure 1). In contrast, patients with ≥2 risk factors had no significant PAV reduction by alirocumab (-1.72% vs. -1.12%, P=0.076, P for interaction=0.009). Conclusions Among AMI patients with no or 1 atherothrombotic risk factor, the addition of alirocumab to high-intensity statin therapy demonstrated greater coronary plaque regression. Patients with fewer risk factors thus appear to be more susceptible for atheroma regression.Change in PAV stratified by risk factors

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p<0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p<0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p<0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

Suboptimal lipid lowering therapy after percutaneous coronary intervention and impact on 1 year outcomes: data from a large contemporary PCI registry

Abstract Background Myocardial revascularisation by percutaneous coronary intervention (PCI) is an effective method for symptom relief in obstructive coronary artery disease on top of pharmacological therapy. In patients with an acute coronary syndrome (ACS), revascularization also leads to improved prognosis. However, patients who underwent PCI are still at high risk for future coronary events such as myocardial infarction, in-stent restenosis or development of new lesions at other locations. According to the current ESC guidelines every patient undergoing PCI should receive at least high-intensity statin therapy to achieve low density lipoprotein cholesterol (LDL-C) target values and to prevent future coronary events. The Zuid-Oost Netherlands Heart Registry (ZON-HR) is an ongoing, multicentre, prospective registry designed to improve secondary prevention after PCI. Purpose To describe differences in lipid lowering therapy after PCI and the influence on major adverse cardiovascular and cerebral events (MACCE) one year after PCI. Methods Since November 2020 data from all patients who underwent PCI in one of the four ZON-HR hospitals were included. Patients with known lipid lowering medication at discharge and 1 year follow-up were selected (N=4272). Patient characteristics, lipid lowering medication at discharge and 1 year follow-up regarding complications were collected. Cross tables and logistic regressions were used to observe baseline differences between patients with and without lipid lowering therapy (LLT) at discharge. A cox regression survival analysis with adjustments for baseline differences was performed to look at differences in MACCE after one year in patients with and without LLT after discharge. Results In 11.9% of the patients LLT was not part of the discharge medication. Patients without LLT were older and had more often chronic coronary syndrome (71.3 ± 10.7 vs 67.6 ± 10.9 and 63.2% vs 43.1%, respectively)(table 1). After one year, MACCE had occurred more often in patients without LLT at discharge after adjustment for baseline differences (HR: 1.51, 95% CI 1.15-1.98) (figure 1). In an additional analysis with only ACS patients even a higher occurrence of MACCE was observed in patients without LLT at discharge (HR: 1.97, 95%CI 1.41-2.76). Conclusion In real-world practice, suboptimal cholesterol management is frequently observed and leads to a higher occurrence of MACCE one year post PCI. Almost 12% of the patients did not have any LLT after PCI. Patients with ACS indication for PCI without LLT after PCI even had worse outcome regarding MACCE after 1 year. More attention should be paid regarding cholesterol management after PCI in order to prevent future coronary events.Baseline differencesMACCE and lipid lowering medication

Lesion-level changes induced by low-density lipoprotein cholesterol lowering therapy in patients with acute myocardial infarction: the pre-specified PACMAN-AMI lesion-level analysis

Abstract Background Previous intracoronary imaging studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments, based on anatomical landmarks and irrespective of the baseline atheroma burden. The effects of lipid-lowering therapy focusing on coronary lesions with advanced atherosclerotic features and at presumably higher risk for future events remains largely unknown. Purpose To provide a lesion-level analysis reporting changes in high-risk atherosclerotic features and plaque phenotypes induced by alirocumab versus placebo in addition to high-intensity statin therapy in nonculprit coronary lesions of patients admitted with acute myocardial infarction (AMI). Methods In this pre-specified lesion-level analysis of the PACMAN-AMI trial, coronary lesions were identified as segments with plaque burden ≥40% defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) images at baseline and 52-week follow-up were manually matched and lesion-level imaging outcome measures were calculated by analysts blinded to treatment allocation and patient clinical data. The evolution of high-risk plaque phenotypes as defined by each imaging modality (IVUS-defined plaque burden ≥70%, NIRS-defined maximum LCBI 4 mm ≥400, OCT-defined thin-cap fibroatheroma <65µm) was investigated. Results Overall, 591 lesions with available baseline and follow-up imaging were included. Of these, 287 were identified in 118 patients (214 vessels) in the alirocumab arm, and 304 lesions were identified in 127 patients (239 vessels) in the placebo arm. At lesion-level, mean change in percent atheroma volume (PAV) by IVUS was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02 [-3.00 to -1.05], p<.001), substantially greater than that at vessel-level (Figure 1). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36 (-4.98 to -1.75, p<0.001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 in the placebo arm (difference, +0.21, 0.01 to 0.41, p=0.036), whereas arterial remodeling was similar between arms (-0.73±1.61 in alirocumab vs -0.63±1.31 in placebo group, p=0.482). Among lesions with high-risk plaque phenotypes at baseline, those in the alirocumab arm more frequently showed a more stable and less lipid-rich plaque phenotype at follow-up than those in the placebo arm (Figure 2). Conclusions At lesion-level, intense lipid-lowering therapy with alirocumab in addition to high-intensity statin therapy induced extensive PAV regression, substantially greater than described in previous vessel-level analyses. Compared to statin therapy alone, alirocumab treatment was associated with a greater enlargement of the lesion MLA, similar negative arterial remodeling, and a more frequent transition of high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes.Figure 1.Figure 2

Impact of High-Intensity Statin on Atrial Fibrillation After Off-Pump Coronary Artery Bypass.

There is uncertainty regarding the impact of high-intensity statins on postoperative outcomes in patients undergoing surgical myocardial revascularization. This study was conducted to evaluate the impact of high-intensity statin treatment on the occurrence rate of new-onset postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Six hundred thirteen patients (66.8±9.8 years, male:female = 476:137) who underwent isolated OPCAB were retrospectively enrolled. Hypertension (n = 409, 66.7%), diabetes mellitus (n = 343, 59.6%) and chronic kidney disease (n = 138, 22.5%) were common comorbidities. Statins and beta-blockers were administered to all patients until the day of surgery and resumed within 6 hours after surgery. Risk factors associated with POAF were analyzed, including the use of high-intensity statins (atorvastatin 40 mg-80 mg or rosuvastatin 20 mg), as well as baseline characteristics and preoperative risk factors. High-intensity statins were used in 158 patients (25.8%). POAF occurred in 184 patients (30.0%). The use of high-intensity statins was not correlated with preoperative levels of low-density lipoprotein (P = 0.135) or high sensitivity C-reactive protein (P = 0.365). Multivariate logistic regression analysis revealed that the use of high-intensity statins was significantly associated with a reduced occurrence of POAF (P = 0.022, odds ratio [95% confidence interval] = 0.592 [0.378-0.926]). Age, acute coronary syndrome, insulin-dependent diabetes mellitus and chronic kidney disease were also significantly associated with POAF. Preoperative administration of high-intensity statins was associated with a 41% reduction in the occurrence rate of POAF in patients who underwent OPCAB.

Clinical reality and challenges with familial hypercholesterolemia patients' management. 2024 results from the Regional Center for Rare Diseases (RCRD) Registry in Poland

BackgroundDespite advancements in early diagnosis and effective medications in last decade, most heterozygous familial hypercholesterolemia (heFH) patients still fail to achieve their low-density lipoprotein cholesterol (LDL-C) goals and remain at residual cardiovascular disease risk. We present recent data from the regional FH registry in Poland, highlighting the challenges and real-life clinical management of FH patients. MethodsThe registry is held at the Regional Centre for Rare Diseases, founded in 2016, at the 2nd largest, supraregional hospital in Poland, where >80 different rare diseases in patients from all over Poland are diagnosed and treated, including phenotypically or genetically diagnosed FH patients. Our analysis focused on both children and adult FH patients, excluding those treated with inclisiran due to a small sample size (n = 5). ResultsWe studied 173 consecutive heFH patients, median age for adult population was 40 years (range: 27–57), of whom 56.14 % were women. Among the population, 82.1 % were adults (n = 142), and 31 were children (17.92 %; median age 9 (8–13), females 58.16 %). Children exhibited lower total cholesterol and triglyceride levels compared to adults, with no significant differences in LDL-C and high-density lipoprotein cholesterol (HDL-C) levels. Molecular diagnosis in the whole population revealed that 76.6 % had an LDL receptor (LDLR) mutation, while 23.4 % had an apolipoprotein B (APOB) mutation. Risk assessment categorized patients into high (70.7 %), very high (22.1 %), and extremely high (7.1 %) risk groups. Triple therapy achieved treatment goals in 61.76 % of adults and 70.97 % of children. At baseline, 36.62 % of adult patients were not using statins. High-intensity statin therapy combined with ezetimibe was initiated for the remaining patients. Only 3.33 % of patients avoided statins due to complete intolerance. Ezetimibe was used in 57.27 % of patients (mostly in combination therapy), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were prescribed for 28.17 % FH patients. In adults receiving statin and ezetimibe therapy, median achieved LDL-C was 141 mg/dl (107–184). For triple therapy, median achieved LDL-C was 52.5 mg/dL (32–86.5). Overall median achieved LDL-C in the study population was 99.5 mg/dl (57.5–145.4). PCSK9 inhibitors reduced LDL-C by 165.6 mg/dl. Combination therapy did not significantly alter baseline lipoprotein(a) (Lp(a)) levels (p = 0.134), and PCSK9 inhibitors led to a mean Lp(a) reduction of 18.66 mg/dl (45 % reduction; p = 0.013). Multivariable regression analysis identified key factors for achieving LDL-C targets in FH patients: DLCN total score, DLCN category, ezetimibe use, and PCSK9 inhibitors. ConclusionsIn Poland, FH patients are often diagnosed too late (usually over 40 years of age), and many still do not reach their LDL-C goals. Combination LLT double or triple therapy significantly increases the likelihood of achieving LDL-C targets – even up to fivefold. Therefore, unrestricted access to PCSK9 inhibitors for all FH patients is crucial, without the current limitations imposed by drug reimbursement programs like B101.