Lowering Therapy Research Articles

Intensive lipid - lowering therapy is highly cost effective in patients with ST - elevation myocardial infarction: a two - year follow - up of Jena auf Ziel

Abstract Background Jena auf Ziel - "JaZ" - is a prospective cohort study in which early combination therapy with atorvastatin 80mg and ezetimibe 10mg was initiated on admission in all patients with ST - elevation myocardial infarction (STEMI). Lipid - lowering therapy (LLT) was escalated during follow – up with bempedoic (BA) acid and PCSK9 - inhibitors (PCSK9 - I) if serum LDL - C was not within the ESC / EAS goal of 1.4mmol/L or less. Methods and objectives We collected economic and clinical data, including in - hospital costs and length of stay. Costs related to LLT were derived from a pharmaceutical directory for Germany. Follow – ups were conducted either by the outpatient lipid clinic through scheduled appointments or through routine standard care provided by general practitioners (GPs), according to the patients' preferences. In this secondary analysis of "JaZ" we analyzed cost - effectiveness of intensive LLT therapy compared to a less effective LLT approach within the first 24 months after the index event. Results A total of 85 (85.9% men, age: 64.4 ± 13.1 years) consecutive patients were included in this study. Overall, 631 hospital days accumulated for these 85 STEMI - patients. Total cumulative costs of these stays were 802.185,13 EUR (Figure 1). 24 months after discharge, 96.3% of the patients were on statins (atorvastatin: 67.9%; rosuvastatin: 25.9%), 87.7% on ezetimibe, 17.3% on BA and 6.2% on PCSK9 - I with intermittent adjustments by the two outpatient clinics. A mean LDL - C serum reduction of 1.78 ± 1.42 mmol/L could be measured. During the 24 months of follow – up, the total costs for LLT amounted to: 35.495,78 EUR (average per case: 417,59 ± 100,49 EUR) for statins and ezetimibe; 19.983,87 EUR (average per case: 1.492,09 ± 480,97 EUR) for BA and 59.308,32 EUR (average per case: 11.861,66 ± 1.535,62 EUR) for PCSK9 - I (Figure 1). MACE occurred in 10 patients (12.3%) that required a second hospital treatment with additional costs of 73.411,17 EUR (Figure 1). Patients with MACE during follow - up exhibited a shorter duration within the target LDL - C range compared to those without MACE (58.1 ± 29.9% vs. 79.1 ± 28.1%; p < 0.05) (Figure 2). Additionally, their LDL - C levels after 24 - months were higher (2.04 ± 1.26 mmol/L vs. 1.27 ± 0.47 mmol/L; p < 0.001) (Figure 2). Patients with MACE had lower associated costs for LLT compared to patients without MACE (547.04 ± 475.93 EUR vs. 2.562,29 ± 3.170,20 EUR; p < 0.05). Incorporating the additional costs associated with MACE for the subsequent hospital stay, the overall costs for a more expensive LLT however proved to be less and thus highly cost - effective (2.562,29 ± 3.170,20 EUR vs. 7.921,25 ± 4.140,53 EUR; p < 0.01) (Figure 2). Conclusion Intensive lipid - lowering therapy within the first 24 months after STEMI is highly cost effective compared to a less effective lipid - lowering approach.

Long-term continuation to pharmacological treatment for secondary prevention after a myocardial infarction: a register study

Abstract Background Pharmacological treatment for secondary prevention after acute myocardial infarction (MI) is crucial to prevent new events. Several studies report inconsistence and need for improvement of pharmacological treatment. Study follow-up is often less than 10 years and showing that continuation to drug treatment decreases with time. Objective To study long-term follow-up of nationally guideline recommended medical therapy (GDMT) for secondary prevention after a myocardial infarction. Method The study population consisted of individuals aged 18-84 years, who were hospitalized for a MI between January 2006 and December 2022 and were followed up to 16 years. The study subjects were identified through the National Inpatient Register and linked to the Prescribed Drug Register. Four classes of drugs were analyzed: antiplatelet/anticoagulant therapy, lowering therapy, betablockers and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). Time-updated survival analyses were used to investigate the relationship between continuation of preventive pharmacological treatment and mortality and recurrent MI after an acute MI. Results A total number of 139 413 individuals (mean age 69.1±10.6) were included and 33.3% were female. At baseline 51.2% had hypertension, 21.5% diabetes mellitus and 15.2% heart failure. All prescriptions of GDMT were decreased significantly after hospitalization after MI and during first years and remained plateau (figure 1). During follow-up 55487 persons died (39.8%, event rate 5.81 per 100 person years [95% CI 5.76-5.86]). Medication with antiplatelets/anticoagulantia, ACEi/ARB and statins decreased risk of all cause-mortality and myocardial infarction [HR 0.83 [95% CI 0.79-0.86], p-value <0.001, HR 0,79 [95% CI 0.77-0.83], p-value <0.001, HR 0.70 [95% CI 0.67-0.73], p-value <0.001) respectively. Conclusion Pharmacological treatment as a part of secondary prevention remained greatly underutilized both shortly and during long-term after MI. Usage of antiplatelets or antigulantia, ACEi or ARB and statins decreased the risk of all-cause mortality and recurrent myocardial infarction.

Semaglutide for the secondary prevention of cardiovascular disease in people with overweight or obesity, but without diabetes: a cost-effectiveness analysis

Abstract Background The recently published trial, SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) [1], was the first study to demonstrate that the glucagon-like peptide 1 receptor agonist, semaglutide, was superior to placebo in reducing the risk of major cardiovascular events in people with existing cardiovascular disease (CVD) and a body mass index of ≥27kg/m² but without diabetes. Despite the promising clinical benefits, the high cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. Purpose To explore whether use of semaglutide in addition to standard care (background use of lipid lowering, anti-hypertensive and/or anti-platelet therapies) for the secondary prevention of CVD in people with overweight or obesity is cost effective from the Australian healthcare perspective. Methods A Markov model was developed based on the SELECT trial, to evaluate the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events (MI or stroke) or dying. Treatment efficacy, transition probabilities, and utilities were derived from the SELECT trial and published literature. Costs were obtained from Australian sources. The cost of semaglutide at a dosage of 2.4 mg/week (in line with SELECT) was estimated to be ~A$80 per week or A$4175 per year. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. All outcomes and costs were discounted by 5% per year. Costs are reported in 2023 Australian dollars (A$). Results Over a 20 year time horizon, treatment of 1000 hypothetical subjects with overweight or obesity and existing CVD with semaglutide compared to placebo prevented 126 non-fatal CVD events and 81 deaths, and yielded an additional 0.46 discounted life years and 0.48 discounted QALYs per person. The difference in total discounted costs was A$43,955 per person. This equated to ICERs of A$99,853 per YoLS and A$96,055 per QALY gained. Conclusions Assuming a willingness-to-pay-threshold of A$50,000 per QALY gained, semaglutide would not be considered cost-effective for the secondary prevention of CVD in people with overweight or obesity in Australia at current prices. A price reduction of 52% to less than A$2000 per year would be required for it to be considered a cost-effective treatment strategy in this setting. Given the modest event rates reported in SELECT, cost-effectiveness is likely to improve if use of semaglutide is targeted to higher risk groups. Moreover, SELECT primarily focused on cardiovascular benefits, however data supporting the impact of semaglutide on a number of other weight-related complications are anticipated and will inform a more holistic understanding of its cost effectiveness.

Lipid lowering therapy in patients aged 90 years or older with acute myocardial infarction:a multicenter cohort study

Abstract Background Lipid-lowing therapy significantly reduce adverse cardiovascular events in patients with acute myocardial infarction (AMI). However, evidence regarding the efficacy of lipid-lowing therapy in extremely elderly patients with AMI is limited. Purpose This study aims to evaluate major adverse cardiovascular events (MACCE) at 1 year in relation to taking lipid-lowing therapy (statins) among patients aged 90 years or older. Methods The data for this study were derived from a retrospective cohort comprising patients admitted to secondary or tertiary hospitals from 2010 to 2023. Patients were grouped by lipid-lowing therapy: statins group (n=549) and not taking statins group (n=811). The primary endpoint was MACCE, a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, at 1 year. Secondary endpoints included cardiac death (CD), stroke, and recurrence of myocardial infarction at 1 year. Inverse probability treatment weighting (IPTW) based on propensity scores was performed to balance baseline characteristics. A multivariate adjusted Cox proportional hazard model evaluated the association between lipid-lowing therapy and clinical endpoints. Results Of the 1,360 patients, 77.2% were men, and the median age was 92 years. During 1 year follow up, 35.3% of patients experienced MACCE, and 28.7% died due to CD. After IPTW, the incidence of MACCE was lower in the statins group compared to the non-statins group (33.3% vs. 42.6%, p=0.036), as was 1- year mortality due to CD (26.2% vs.35.9%, p=0.021). However, there were no differences in the incidence of stroke (2.8% vs. 4.5%, p＞0.274) or recurrence of myocardial infarction (4.7% vs. 5.1%, p=0,855) at 1 year. Kaplan-Meier analysis showed a lower probability of 1-year MACCE and CD in the statins group (log-rank test, p<0.001). Multivariate Cox regression analysis demonstrated that statin therapy reduced the incidence of MACCE (aHR 0.67; 95%CI, 0.40–0.91; p=0.009) and 1-year CD (aHR 0.63; 95%CI, 0.45–0.87; p=0.005). Conclusions Lipid-lowering therapy with statins was associated with a significantly lower risk of 1-year MACEE and cardiac death in elderly patients aged over 90 years with AMI. These findings support the use of lipid-lowing therapy in elderly individuals.

Implications of a new clinical classification of acute myocardial infarction

Abstract Background The Universal Definition of Myocardial Infarction has provided standardisation of the diagnostic criteria for myocardial infarction. However, there remain significant challenges in adopting some of the current recommendations in practice. The diagnostic criteria for type 2 myocardial infarction identify a heterogenous group of patients with variable clinical outcomes and no clear treatment implications to date. Purpose To determine the implications of a new clinical classification for myocardial infarction with more objective diagnostic criteria using cardiac imaging.(1) Methods In a prospective cohort study,(2) patients with type 2 myocardial infarction underwent coronary angiography and cardiac magnetic resonance imaging or echocardiography. The new classification was applied to identify (a) spontaneous myocardial infarction due to acute coronary pathology, (b) secondary myocardial infarction precipitated by acute illness in the presence of obstructive coronary artery disease, a new regional wall motion abnormality or infarct pattern scarring, and (c) no myocardial infarction in the absence of obstructive disease or new myocardial abnormality. The diagnostic outcome was the proportion of patients with type 2 myocardial infarction reclassified as having spontaneous, secondary or no myocardial infarction by the new clinical classification. The prognostic outcome was a composite of all-cause death, any recurrent myocardial infarction, or heart failure hospitalisation during follow up. Results In 100 patients (65 years, 43% women) with type 2 myocardial infarction, the new classification identified 25 and 31 patients with spontaneous and secondary myocardial infarction, respectively, and 44 without myocardial infarction (Figure 1). Compared to patients without myocardial infarction, those with secondary myocardial infarction were older, had more risk factors, and higher troponin concentrations (P<0.05 for all). In patients who underwent cardiac magnetic resonance imaging, there was evidence of infarct-pattern late gadolinium enhancement in 95% (19/20) and 60% (15/25) of patients with spontaneous and secondary myocardial infarction, respectively, which was more likely to be transmural in the former. In patients reclassified as secondary myocardial infarction, just 45% and 58% were established on aspirin or a lipid lowering therapy. During a median follow up of 4.4 years, death, myocardial infarction or heart failure hospitalization was more common in secondary myocardial infarction compared to those without myocardial infarction (55% [17/31] versus 16% [7/44], P<0.001; Figure 2). Conclusions A new clinical classification of myocardial infarction informed by cardiac imaging would reduce the diagnosis of myocardial infarction in acute illness and identify those patients at highest risk who are most likely to benefit from treatment.Figure 1:Alluvial plotFigure 2:Kaplan Meier curve

Efficacy of combination lipid lowering therapy in achieving low density lipoprotein cholesterol targets after one month of event in patients with acute coronary syndrome

Abstract Introduction Rapid reduction in low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of recurrent events in patients with acute coronary syndrome (ACS) with benefits proportional to LDL-C reduction. Early use of combination lipid-lowering therapy (LLT) is therefore recommended. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-intensity statins (HIS) improve LDL-C goal attainment but are unaffordable for many patients in India and worldwide. Purpose We share our experience with the use of dual RE (rosuvastatin plus ezetimibe) and triple REB (rosuvastatin plus ezetimibe and bempedoic acid) combination LLT in patients admitted with ACS. Methods All ACS patients admitted to our institute over one year (January 2023 to December 2023) were considered in this retrospective analysis. Those with unavailable lipid profile reports, either at the time of ACS or at 1-month follow-up, were excluded. Clinical and laboratory details were obtained from hospital records. The primary objective was to assess the percentage change in LDL-C levels from index event to 4 weeks follow-up. Results A total of 299 patients were included, out of which 60 were on HIS alone, 71 were on RE, and 168 were on REB (Figure). The majority (99%) of patients in the REB group were statin naïve, compared to the other two groups. The baseline mean LDL-C levels at the time of the index event were 95.3+30.5, 103.2+39.6, and 115.6+32.9 mg/dl, respectively (p<0.001) (Table). The mean LDL-C levels at four weeks post-ACS reduced to 52.9+21.2, 45.9+20.5, and 43.7+15.4 mg/dl, respectively (p<0.01). The percentage reduction in LDL-C level was 44.4%, 55.5%, and 62.2%, respectively (p<0.001). REB enabled 70.8% and 95.2% of patients to achieve the Lipid Association of India, and American College of Cardiology recommended LDL-C targets of <50 mg/dl and <70 mg/dl within 4 weeks. These target levels were achieved in 67.6% and 88.7% of patients on the dual RE therapy and 50% and 81.6% of patients, respectively, on HIS alone. Conclusion Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen compared to costly PCSK9i therapy.Figure.Lipid lowering strategies usedComparison of study groups

Comparative efficacy of colchicine and intensive LDL-C lowering in patients with ASCVD receiving statins: a network meta-analysis of randomised controlled trials

Abstract Background Adding intensive low-density lipoprotein cholesterol (LDL-C) lowering treatments or colchicine to statins resulted in additional cardiovascular benefits. However, the relative efficacy and priority of these agents are unclear. Purpose We aimed to compare the effects of these supplementary agents on cardiovascular outcomes in patients with atherosclerotic cardiovascular diseases (ASCVD) receiving statins. Methods We performed a systematic review and frequentist network meta-analysis on randomized controlled trials. The primary efficacy endpoint was the main adverse cardiovascular event (MACE), and the secondary efficacy endpoints were myocardial infarct, stroke, coronary revascularization, cardiovascular death and all-cause mortality. The safety endpoints were treatment discontinuation and non-cardiovascular death. Colchicine was used as reference treatment. Random-effects model was used in case of high heterogeneity, the fixed-effects model was preferred otherwise. We ranked the comparative effects of all drugs with surface under the cumulative ranking (SUCRA) probabilities. Results 17 trials totaling 85823 participants treated with colchicine, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, Niemann-Pick C1-like 1 protein (NPC1L1) inhibitor and ATP citrate lyase (ACL) inhibitor were included. Compared with colchicine, NPC1L1 inhibitor was associated with increased risk of MACE (risk ratio [RR]: 1.39, 1.21-1.59), stroke (RR: 1.81, 1.09-3.00) and coronary revascularization (RR: 1.36, 1.11-1.68), and PCSK9 inhibitor was associated with increased risk of MACE (RR: 1.27, 1.10-1.46). However, NPC1L1 inhibitor (RR: 0.68, 0.48-0.96) and PCSK9 inhibitor (RR: 0.64, 0.44-0.93) were associated with reduced risk of non-cardiovascular death in comparison to colchicine. PCSK9 inhibitors had a lower risk of MACE (RR: 0.91, 95% CI: 0.85-0.98) and coronary revascularization (RR: 0.89, 95% CI: 0.81-0.97) compared with NPC1L1 inhibitor. Although no regimen prolonged survival, colchicine had the lowest rank at non-cardiovascular death and the worse performance on all-cause mortality. Conclusions In patients with ASCVD receiving statins, inflammation-inhibiting with colchicine seems to be superior to intensive LDL-C lowering therapy with PCSK9 inhibitor or NPC1L1 inhibitor in cardiovascular prevention. However, using colchicine as an alternative to intensive lipid-lowering therapy may need to be weighed against the greater cardiovascular benefits and the potential harms of higher non-cardiovascular death. Given the worse performance of colchicine on survival based on current evidence, colchicine may be more appropriate for patients who have been treated with intensive LDL-C-lowering agents but still have recurrent cardiovascular events.Forest plots of included agentsRadar plot of treatments based on SUCRA

Comparison of cardiovascular disease risk assessment tools in primary prevention patients with raised lipoprotein(a)

Abstract Background Genetically inherited lipoprotein (a) (lp(a)) is an independent cardiac risk factor. The approach to cardiovascular disease (CVD) risk modification is, however, uncertain. Current CVD risk calculators do not take lp(a) into account and guidance suggests binary treatment decisions based on presentation of lp(a) without considering other risk factors. A new CVD risk assessment tool has been developed which includes lp(a) concentration, Lp(a) Clinical Guidance (lpaclinicalguidance.com). Purpose The aim was to compare the CVD risk estimations and management impact, over both 10 years and lifetime, using the HEART UK consensus statement, QRISK3, Lp(a) Score, Score-2, Score-2 OP, and LIFE-CVD assessment tools in 20 primary prevention patients with raised lp(a). Methods This was a retrospective analysis from an existing database, recruited through lipid and cardiology outpatient services, with raised lp(a), and no history of CVD. A random selection with a broad range of lp(a) concentrations were chosen. The 10-year risk threshold to treat was based on current NICE guidance at 10% and, in the absence of consensus, a lifetime risk threshold of 25%. Lp(a) was measured by a reference clinical laboratory using a Roche platform (Denka Seiken reagent, isoform insensitive). Results The subset (n=20) included patients with lp(a) ranging from 64 nmol/L to >720 nmol/L, aged 20 to 78 (12 females). Risk assessment tool age restrictions prohibited risk estimation in all patients (explaining the variation in denominator below). Figure 1 shows a comparison of 10-year risk assessment tools, figure 2 lifetime risk. HEART UK guidance would indicate 90% of patients (18/20) were eligible to commence lipid lowering therapy, however, all patients would have treatment indicated based on Lp(a) Score (16/16). Using Score-2, no patients would have treatment indicated (0/6). Only 25% of patients (1/4) would have treatment indicated using Score-2 OP despite a minimum age criterion that alone introduces a major CVD risk factor. Of the remaining risk estimation tools: LIFE-CVD, QRISK3 lifetime risk, and QRISK3 10-year risk indicated 85% (11/13), 50% (8/16), and 38% (6/16) of patients, respectively, would have treatment indicated. Conclusions In primary prevention patients with raised lp(a), CVD risk estimation and decision-making is impaired by discrepancies in risk assessment tools. There may be underestimation in CVD risk, and subsequently under-treatment, with principal use of QRISK3 10-year risk to guide lipid lowering therapy. Lifetime CVD risk may be underestimated by QRISK and LIFE-CVD proportionally to the degree of elevation of lp(a). Risk assessment is imperfect; population data can only provide limited information when applied to an individual and the wide discrepancy found here calls into question the validity of risk estimation formulae in this population, or alternatively provides a range of tools for clinicians to select to suit the question asked.

LDL-C target attainment and statin use in patients with ASCVD, familial hypercholesterolaemia, and those otherwise at moderate/high-risk of ASCVD in australian general practice (SCOPE-GP)

Abstract Background The proportion of Australian general practice patients not attaining low-density lipoprotein cholesterol (LDL-C) goals is not well described. The SCOPE-GP study evaluated duration of LDL-C exceeding treatment goals, statin use and discontinuation rates in patients with atherosclerotic cardiovascular disease (ASCVD), without ASCVD events but at moderate/high-risk, and familial hypercholesterolemia (FH). Methods This population-based retrospective cohort study used de-identified medical records of adult patients captured in the IQVIA GP-EMR database. Patients were indexed at the earliest date of ASCVD, FH, or hyperlipidemia diagnosis from January 1, 2010 to June 30, 2022, with a variable follow-up period from index to June 30, 2022. Ascertainment of study cohort was based on the 2021 ESC/EAS guidelines and Framingham Risk Equation. LDL-C test result levels were extracted per patient, summarised and analysed. Patients were stratified based on their test results at latest results/closest to censor date. Average time above target levels is the proportion of number of days above LDL-C target levels over total number of follow-up days for each patient. A Poisson distribution was fitted to estimate 95% confidence interval. Lipid lowering therapies (LLT) were stratified by (ASCVD, FH and moderate/high risk of CVD) at last visit/censor date. Combination of LLT were defined as prescriptions for fixed dose combinations or ≥2 separate scripts of LLT from different classes within 180 days from last visit/censor date (look back period). Discontinuation is defined as no statins were prescribed again after the last script for 270 days or more, limited to the first occurrence. Results The average time with LDL-C levels above target was 1077.5 days in ASCVD patients (n=2,688), 938.6 days in moderate-risk ASCVD (n=37,003), 980.9 days in high-risk ASCVD (n=85,199), and 900.8 days in FH (n=279). The proportion of days above target level for all four cohorts is described in Figure 1. Among 107,552 patients with recorded LDL-C levels ≥1.8mmol/L at their last visit/censor date, 30.9% were on statin monotherapy and 1.0% were on statin+ezetimibe. Statin use was highest in ASCVD patients (65.4%), followed by FH (49.5%), high risk (40.0%) and moderate risk subjects (29.5%) (Table 1). Statin discontinuation rates were 60.3%, 76.3, 66.1%, and 65.8% in these groups, respectively. The predominant reason for statin discontinuation was non-specific adverse drug reactions (12.2% ASCVD, 11.7% moderate-risk, 13.2% high-risk and 17.9% FH). The proportion of subjects contraindicated to statins was highest in moderate risk subjects (0.05%). Conclusions Prolonged periods of elevated LDL-C and high statin discontinuation rates were prevalent among at-risk individuals in Australian primary care. This underscores a significant ASCVD burden that could be prevented with more active lipid management.

Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)

Abstract Introduction Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries. Aim To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru. Methods Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: <500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis. Results The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800). Conclusions Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.

Lipoprotein (a) and lipidemic parameters in PCSK-9 inhibitor patients. Experience from a specialized centre in Greece

Abstract Background Previous studies have reported an association between Proprotein Convertase Subtilsin-kexin type 9 (PCSK-9) inhibition and levels of lipoprotein a [Lp (a)], having a possible effect on the cardiovascular benefit achieved by their use. The purpose of this study was to investigate the effect of PCSK-9 inhibitor use in Lp (a) and other lipidemic parameter levels in the population of a specialized Lipids Clinic during a follow up period of 24 months. Methods We enrolled 143 (80 males, mean age 60 years old) patients who were on PSCK-9 inhibitor treatment from the outpatient lipid clinic of our hospital. Information were obtained regarding the presence of coronary artery disease (CAD) and CAD risk factors. CAD was present in 72 patients (63%), Familial Hypercholesterolaemia (FH) in 97 patients (85%) and 20 (18%) patients suffered from statin intolerance. Patients were on triple lipid lowering therapy (statin plus ezetimibe plus PCSK-9 inhibitors) except for those with statin intolerance who were either on dual therapy (ezetimibe plus PCSK-9 inhibitors, N=8) or single PCSK-9 inhibitors therapy (N=10). Lp (a) levels and lipid parameters such as Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglycerides (TG) were measured at baseline, 3 months, 12 months and 24 months of treatment. Additionally, patients were categorized according to baseline Lp (a) levels in two groups, Group 1 (<70mg/dl) (N=62), Group 2 (≥70 mg/dl) (N=26). A comparison of the response in lipid parameters between these two groups was performed. Results Mean value for Lp (a) in the whole population was 54mg/dl, 48mg/dl, 44mg/dl, and 45mg/dl at baseline, 3, 12 and 24 months, respectively. T test analysis revealed a significant reduction in Lp (a) levels after 12 months (P<0.05) There was also a significant reduction in LDL levels at all time points (165mg/dl to 78mg/dl, 85mg/dl, 78mg/dl respectively, P<0.05), a reduction in triglyceride levels at 3 and 12 months (125mg/dl to 110mg/dl, 108mg/dl respectively, P<0.05) and an increase in HDL levels after 12 months (50mg/dl to 53mg/dl, P<0.05). Moreover, in Group 1, the response in LDL levels was higher after 12 months of treatment with PCSK-9 inhibitors (158mg/dl to 69mg/dl, P<0.05) compared to Group 2 (155mg/dl to 86mg/dl), indicating that high levels of Lp (a) seem to define the response to treatment. Colclusions Besides the detrimental effect in LDL levels, PCSK-9 inhibition has an impact on HDL and TG levels. Lp (a) was also reduced indicating an additional important effect of this inhibition. While higher levels of Lp (a) seem to correlate with poorer response to treatment, our findings enhance the already known importance of Lp (a) as a prognostic factor.

Combination of moderate-intensity statins and ezetimibe versus high-intensity statins alone for primary prevention of cardiovascular events

Abstract Background Combination of a moderate-intensity statin with ezetimibe can lead to similar reductions in cardiovascular events as monotherapy with a high-intensity statin in patients with established atherosclerotic cardiovascular disease (ASCVD). The comparative effectiveness of these two cholesterol-lowering strategies in the primary prevention setting is unknown. Purpose To compare incident ASCVD events associated with a combination of moderate-intensity statin and ezetimibe versus monotherapy with a high-intensity statin in adults without prior history of cardiovascular disease. Methods We conducted a new-user active comparator retrospective population-based cohort study in Canada. We included all adults aged ≥ 67 years (eligible for drug coverage) with a first prescription of either a combination of moderate-intensity statin with ezetimibe ("combination therapy") or high-intensity statin alone between January 2010 and December 2022. Patients were excluded if they had not received any prior lipid lowering therapies or had a history of myocardial infarction (MI), stroke, heart failure, peripheral vascular disease or prior coronary revascularisation at any time before or within 3 months of treatment initiation. The primary outcome was a composite of all-cause death, hospitalization for MI or stroke, or coronary revascularization. An inverse probability of treatment weighting propensity score was used to account for confounding (demographics, comorbidities, laboratory tests, other medications). Results Among 67,884 patients (mean age: 74.0±5.5y; 53% females), 8,798 (13%) initiated combination therapy and 59,086 (87%) initiated a high-intensity statin. At 1 year, after weighting, the mean achieved LDL-C was ~1.9 mmol/L in both groups. The median follow-up was 6.5 years. The cumulative incidence of the primary outcome at 10 years in the weighted cohort was 32.7% in the combination therapy group and 36.1% in the high-intensity statin group (HR: 0.87; 95% CI: 0.82 to 0.92; p<0.001; absolute risk reduction: 3.5%; 95% CI: 0.8 to 6.1; Figure 1). This result was primarily driven by a lower risk of all-cause death (HR: 0.85; 95% CI: 0.80 to 0.91; p<0.001; Figure 2) and stroke (cause-specific [cs] HR: 0.86; 95% CI 0.74 to 0.99; p=0.04), whereas no differences were observed in the risk of MI (csHR: 0.97; 95% CI: 0.82 to 1.15) or coronary revascularization (csHR: 0.97; 95% CI 0.85 to 1.11). Conclusion The combination of moderate-intensity statins with ezetimibe was associated with a lower risk of incident ASCVD compared with high-intensity statins alone among primary prevention patients in a real-world setting. These results were driven by a lower risk of all-cause death and stroke, but not coronary events. The influence of statin intolerance on the allocated strategy and adherence to therapy cannot be addressed in this analysis, which, along with verifying these estimates, may be best determined in a prospective randomized trial.

Management of children with heterozygous familial hypercholesterolemia worldwide: a meta-analysis

Abstract Background HeFH is one of the most frequent monogenic disorders in the world, leading to premature ASCVD. Purpose The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of LDL-C goal in heFH children. Methods The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (<3.5 mmol/L/130 mg/dL). Results A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p<0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by PCSK9 inhibitors, statins in monotherapy, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p<0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p<0.001) and failed to reach the goal treatment (<3.5 mmol/L) by 12.6% (95%CI, 12.4 – 12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between >10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal <3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p>0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. Conclusions Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.Lipoproteins reduction with LLT.Goal achievement and therapy safety.

Lipid lowering therapy and the unmet targets in Indian patients with angiographically proven coronary artery disease: results from the OLS registry

Abstract Introduction The Lipid Association of India (LAI) 2020 guidelines classify patients with established atherosclerotic cardiovascular disease in either very high-risk or extreme-risk groups and recommend that intensive lipid-lowering therapy (LLT) should be administered to such patients to achieve a target low-density lipoprotein cholesterol (LDL-C) level below 50 mg/dl at least (preferably < 30 mg/dl in extreme risk groups). Purpose This study aimed to assess the achievement of the LAI-recommended LDL-C goals in patients with angiographically proven coronary artery disease (CAD). Methods The Optimization of LDL-C in the Stable CAD (OLS) registry started in August 2023 in 10 interventional cardiology centers across Northern India. Interventional cardiologists (ICs) were treating all enrolled patients with angiographically proven stable CAD, and data were collected at a single visit, including the most recent LDL-C and the LLT in the preceding three months of that LDL-C reading. The primary outcome was achieving the LAI-recommended LDL-C goal of <50 mg/dl. The achievement of the American College of Cardiology (ACC) recommended goal of <70 mg/dl was also assessed. Results A total of 1860 patients with angiographically proven CAD were enrolled in this ongoing registry over four months (August 2023- November 2023). The mean age of the study population was 60.2 + 9.2 years, and 79% were males. 30.3% of patients had Diabetes mellitus (DM), 36.1% had hypertension (HTN), 42.3% were obese (body mass index > 25kg/m2), and 17.8% of patients were current smokers. 74.2% of patients had a history of myocardial infarction, while 76.7% had undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Rosuvastatin was the statin prescribed in 59.4% of patients, while atorvastatin was prescribed in 37.2%. 1270 (68.3%) of patients were taking high-intensity statin (HIS) therapy (either 20-40 mg rosuvastatin or 40-80 mg atorvastatin). Only 22 (1.2%) patients took other lipid-lowering agents, including ezetimibe, bempedoic acid, and fibrates. None of the patients were using PCSK9 Inhibitors. Only 482(25.9%) patients achieved their LAI recommended goal of LDL-C <50 mg/dl, 113(6.1%) achieved LDL-C < 30 mg/dl, while 863(46.4%) achieved ACC goal of <70 mg/dl. Notably, only 62(3.3%) patients were not taking any lipid-lowering treatment. Conclusion Results of the OLS study demonstrate the high-risk status of CAD in Indian patients with a high prevalence of DM, HTN, and obesity. Most patients were post-PCI/CABG, mainly because ICs did enrolments. More than two-thirds of patients were taking HIS and very few were not taking any treatment. Despite this, only one-fourth of patients achieved the target LDL-C goals. Greater and early utilization of combination LLT, including HIS and non-statin LLT, is likely needed to reduce these gaps for patients at the highest risk.

Cardiovascular related polypharmacy and its association with liver and kidney impairment amongst individuals on lipid-lowering therapy: a cross-sectional study using primary care data

Abstract Background Individuals with risk factors for cardiovascular disease (CVD) frequently require concurrent treatment with various medications, a phenomenon known as polypharmacy. This study aimed to investigate the association between CVD-related polypharmacy and the presence of liver and kidney impairment amongst patients receiving lipid-lowering therapy within the Australian primary care setting. Methods This study utilised electronic medical records from general practices retrieved between January 2013 and December 2023. Multivariate logistic regression identified independent risk factors associated with CVD-related polypharmacy, defined as the concurrent use of five or more CVD protective medications. The analysis included individuals on lipid lowering therapy who are at risk for CVD. The relationship between CVD-related polypharmacy and the presence of liver and kidney dysfunction was further assessed, defined by exceeding established reference ranges for relevant biomarkers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin, creatinine, and estimated glomerular filtration rate [eGFR]) as per Australian guidelines. Results A total of 13,568 participants (median age: 63 years [IQR 54-72], 54% males) were included. Independent factors associated with CVD-related polypharmacy included diabetes (OR=5.40, 95% CI: 4.96-5.93), chronic kidney disease (CKD) (OR=2.39, 95% CI: 2.00-2.86), hypertension (OR=1.91, 95% CI: 1.75-2.07), and smoking (OR=1.05, 95% CI: 0.97-1.14). Compared to the 18-35 age group, individuals aged ≥80 years displayed a significantly higher likelihood of CVD-related polypharmacy (OR=8.17, 95% CI: 5.47-12.21). While no significant association was observed between CVD-related polypharmacy and liver impairment (OR=1.19, 95% CI: 0.59-2.37), an independent positive association was identified with kidney impairment (OR=1.38, 95% CI: 1.24-1.54), adjusted for established CVD risk factors including age, sex, smoking, diabetes, hyperlipidaemia, hypertension, and CKD. Conclusion This study suggests a positive association between CVD-related polypharmacy and increased risk of kidney impairment in Australian primary care. Further research is warranted to explore potential causal mechanisms and evaluate the efficacy of medication review strategies, enhanced kidney function monitoring, and potential medication deprescribing in managing patients at risk of CVD who are on multiple medications.

Absence of coronary artery disease in high-risk sickle cell anemia patients: a new illustration supporting the protective effect of Bilirubin against atherosclerosis?

Abstract Background Sickle cell anemia (SCA) is associated with both cardiac and systemic vascular disorders, which are the leading cause of morbi-mortality. Although these patients cumulate multiple cardiovascular (CV) risk factors, along with chronic inflammation and endothelial activation, some pre-clinical studies underlined a paradoxical protection against atherosclerosis. Purpose The aim of this study was to evaluate the prevalence of coronary artery disease in a high-risk SCA population. Methods From January 2019 to December 2023, consecutive adult patients with SCA were prospectively included in the DREPACOEUR registry to specifically analyze cardiac structure and function. They all had a comprehensive CV evaluation at steady-state in day-hospital including clinical exam, cardiac imaging, rhythm monitoring along with biology analysis. Only patients that underwent coronary imaging (CT coronary angiogram) were included in this study. Results Ninety patients were included. Mean age was 44±12, 50% were male with a high prevalence of systemic hypertension (57%), obstructive sleep apnea (21%) and 10% smokers. Only one patient had history of diabetes while no dyslipidemia (or lipid lowering therapy) was reported. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 58±5%. Expectedly, patients showed low hemoglobin level 8,7±1.4g/dL with high hemolysis markers. Glomerular filtration rate was 109 [62; 122] mL/min/m² with 21% having chronic kidney disease. Plasmatic LDLc level was low (0.7±0.3g/L, with 20% <0.5g/l) while triglycerides (TG) were highly variable (1.1±0.7mg/dL). Strikingly, no patient showed signs of significant coronary artery disease, with 87% presenting a calcium score of 0, 77% had a CAD-RADS of 0 while no patient was higher than 2. Correlation and linear regression analysis were performed to find independent parameters associated with LDLc and TG. Total bilirubin was the only variable that correlated with both LDLc and TG (R= -0.37, p<0.001 and R= -0.33, p=0.001 respectively). Conclusion Despite systemic vasculopathy and chronic inflammation, ageing SCA patients showed no significant coronary artery disease. These data are in line with pre-clinical studies suggesting a lipid-lowering role of bilirubin and its protective effect against atherosclerosis.

The prevalence, patients characteristics and risk factors of hyper-Lp(a)-emia in the Polish population. The first results from the PMMHRI-Lp(a) Registry

Abstract Background Based on the recent data and existing guidelines Lp(a) is recognized, independent CVD risk factor. However, the knowledge on the prevalence of elevated Lp(a) levels, patients characteristics as well as non-genetic risk factors is scarce from some world regions including from Poland, the largest CEE country. Purpose We aim to present the first results from the Lp(a) registry established in the 2nd largest hospital in Poland - Polish Mother’s Memorial Hospital Research Institute (PMMHRI). Methods The PMMHRI-Lp(a)-Registry was established in 2022. The indications for Lp(a) measurement in the registry are based on the 2021 Polish Lipid Guidelines and new Polish recommendations on the management with elevated Lp(a) (2024). The PMMHRI-Lp(a)-Registry is a part of the being founded Lp(a) National Registry of the Polish Lipid Association. Results Based on the data from 302 consecutive patients (mean age 52.18 years; women 53%) the mean Lp(a) level was 30.3±39.4 mg/dl; it was numerically higher in woman (32.8 mg/dl), but there were no significant sex differences (men: 27.5 mg/dl; p=0.245). There were also no significant differences between those with and without CAD, stroke, HF, cancer, diabetes, kidney disease, and thyroid disease. The significant Lp(a) level difference was observed in those with diagnosed dyslipidemia in comparison to those without (31.9±40.6 vs 17.7±25.8 mg/dl, p=0.044) and in those with the history of myocardial infarction (MI) vs those without (50.1±50.3 vs 28.1±37.5 mg/dl, p=0.004). However, when we divided those with MI on premature vs no premature, no significant difference in Lp(a) level was observed (41,6±41.9 vs 57.6±56.7 mg/dl, p=0.39). Lipid lowering therapy did not significantly affect Lp(a) level, with only significant differences in those treated with ezetimibe (as a part of the combination therapy; 39.5±47.6 vs 27.5±36.3 mg/dl, p=0.027). For selected patients (n=31; 10.3%) with two Lp(a) measurements (mean time distance: 7±5 months) we did not observe any significant visit-to-visit variability (mean difference: 0.81 mg/dl; z=0.256, p=0.262) (Fig. 1). We did not also observe any percentage differences in variables (besides MI history, p=0.017) for different Lp(a) risk groups: 0-30, >30-50, >50-180 and >180 mg/dl. While dividing the population on those with Lp(a) ≤30 mg/dl vs >30 mg/dl, the only differences were seen for dyslipidemia diagnosis (p=0.044) and MI occurrence (6.98 vs 17.24%; p=0.007). Similar pattern was observed while dividing the whole population on those with Lp(a) ≤50 vs >50 mg/dl (Fig. 2). Conclusions These results strongly emphasize that Lp(a) should be measured commonly, as its high level is highly prevalent in patients at the risk both in primary and secondary prevention, what require risk re-stratification and treatment optimization. This is especially important in the regions that characterize of baseline high CVD risk, what refers to most of the CEE countries, including Poland.

Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe, bempedoic acic, and proprotein convertase subtilisin/kexin type 9 (PCSK-9) (synthase-) inhibitors allow for the reduction in LDL-cholesterol in addition to statin therapy. Purpose We aimed to perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. In specific, we evaluated the potential influence of duration of follow-up on the association with mortality endpoints. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe, bempedoic acid, Bococizumab, Alirocumab, Evolocumab, Inclisiran in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of August 2023, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were : "Bempedoic Acid" or "Bococizumab" or "Alirocumab" or "Evolocumab" or "Ezetimibe" or "Inclisiran" and "statin" and "cardiovascular events". Results A total of 123,785 patients from 15 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, ODYSSEY LONG TERM, EWTOPIA 75, PACMAN-AMI, RACING, SIPRE I, SPIRE II, OSLER-1 and OSLER-2, CLEAR HARMONY, CLEAR OUTCOMES, CLEAR SERENITY, CLEAR WISDOM) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 19% risk reduction in cardiovascular events (OR [95%CI]: 0.81 [0.75; 0.86]). Effect sizes were similar for myocardial infarction (0.81 [0.74; 0.89]) and even more pronounced for ischemic stroke (0.77 [0.70; 0.84]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.99 [0.93; 1.04]). Stratifying by follow-up duration of < vs. ≥ 3 years, no improvement in all-cause mortality was observed in both groups (<3 years: 1.04 [0.93; 1.17]; ≥3 years: 0.97 (0.88; 1.06). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Conclusion Intensified LDL-lowering therapy with ezetimibe, bempedoic acic or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. A potential survival benefit was also not observed in studies with follow-up duration of ≥ 3 years.

Changes in lipid lowering therapy one year after percutaneous coronary intervention: data from the large contemporary ZON-HR registry

Abstract Background Patients who underwent percutaneous coronary intervention (PCI) should receive at least high-intensity statin therapy according to current ESC guidelines to prevent ischemic events. However, previous studies have shown that about 80% of the patients using high-intensity statin monotherapy are not reaching the low density lipoprotein- cholesterol (LDL-C) target value of below 1.4 mmol/L. This means that additional lipid lowering therapy is necessary in most patients. The ‘Zuid-Oost Netherlands Heart Registry’ (ZON-HR) is a multicentre, prospective registry designed to improve secondary prevention after PCI by a patient-tailored approach. Purpose To describe changes in lipid lowering therapy one year after PCI in the ZON-HR. Methods Since November 2020 data from all patients who underwent PCI in one of the four participating ZON-HR hospitals were included. In 4811 patients one year follow-up was completed. Patients with known discharge medication and medication at one year after PCI were included in the analyses (n=3487). Combination therapy was defined as having at least two different lipid lowering medications prescribed. The association between predefined variables and combination therapy at one year post PCI was assessed with multivariable logistic regression to adjust for baseline differences. Results The mean age of the patients was 67.7 ± 10.7 years, 72.4% was male and the baseline LDL-C value was 2.7 ± 1.1 mmol/L. While patients with an acute coronary syndrome (ACS) had higher LDL-C values at baseline, they received combination of lipid lowering therapy at discharge less often compared to patients with a chronic coronary syndrome (CCS) (7.9% vs 11.5%, p<0.001) (table 1). After one year, both ACS and CCS patients were treated more often with combination therapy (20.1% vs 23.3%, p=0.047). However, still only about 20% of the patients were receiving combination therapy one year after PCI. In the ACS population, younger patients with higher LDL-C values at baseline and previous myocardial infarction had a higher chance of receiving combination lipid lowering therapy one year after PCI (table 2). Conclusion Additional lipid lowering medication is needed, besides high-intensity statins, in order to reach the strict LDL-C target values in very high risk patients. However, the step-up from mono- to combination lipid lowering therapy only occurs in about 10% of the patients. Lipid lowering combination therapy is prescribed more often in CCS patients compared to ACS patients, both at discharge and one year after PCI.Baseline values and combination therapyPredictors combination therapy at 1 year

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