Lipid-lowering Therapy Research Articles

The difference between guideline based lipid optimisation and real-world practice in a very high risk population

Abstract Background Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor for the progression of cardiovascular disease and early optimisation of lipid lowering therapy following an acute coronary syndrome (ACS) or stroke is associated with improved outcomes. Recent guidelines have advocated the use of combination lipid-lowering therapy and achieving very low LDL-C concentrations.Purpose To identify if optimal lipid management in high risk patients has occurred. Methods A retrospective analysis of high-risk patients with a prior history of ACS or stroke presenting with a further subsequent ACS/stroke from January 2022 to December 2022 in a UK District General Hospital was performed. Lipid lowering therapy in primary care in the 18 months leading up admission, inpatient admission and subsequent 12 month post admission (delivered through the cardiac rehabilitation service post ACS and via primary care post stroke) was compared to our regional secondary prevention lipid lowering pathway. This patient group, with recurrent events, was selected as represents the "very high risk group" and had been through various clinicians multiple times increasing the opportunity to treat to guidance. Results 102 very high risk patients were admitted within the 12 month period. Only 79/102 patients had lipid profile in preceding 18 months and only 19% were compliant with the standard secondary prevention guidelines (20/102 patients high intensity statins), mainly due to reduced intensity statin doses (60%) and no lipid lowering medications (15%). A significant proportion of patients did not have any lipid blood tests during their index admission (no lipid profile 21% in stroke group vs 77% in ACS group) and whilst there was a significant inpatient escalation in lipid therapy this was mainly confined to high dose statins, and seen more clearly in the ACS group (ACS 65% vs stroke 21%). During the 12 months following admission a significant number of patients had no further lipid profiles (21% ACS vs 57% stroke) and minimal further optimisation of lipid management. Further escalation following high intensity statins were rare with only 5 / 102 patients receiving high intensity statin plus ezetimibe, 1 patient receiving statin/ ezetimibe/ PCSK9 inhibitor. Only 45% of patients achieved the guideline target of LDL < 1.8 mmol/L and only 18% achieved the ESC target of LDL <1.4 during 1 year follow up. Conclusion Although lipid guidelines have changed in recent year’s clinical real-world practice locally has not reflected these important developments, even in a very high-risk group patients are not benefiting from established evidence-based interventions. A majority of our ACS patients did not have a lipid profile blood test during their admission highlighting the fact that whilst guidelines have progressed significantly over the last few years the clinical importance of lipid optimisation in practice has not been appreciated by many of the cliniciansResults

An ACNAP survey assessing the cardiology multidisciplinary learning needs to support lipid management

Abstract Background/ Introduction: Reducing LDL cholesterol is a high priority in cardiovascular care but requires knowledge and skills to deliver effectively. Nurses and allied professionals (NAPs) can play a major role in supporting lipid optimisation. Most NAPs will work together with patients prescribed lipid lowering therapies, and some may be more closely involved in initiation and monitoring. The Association of Cardiovascular Nursing and Allied Professionals (ACNAP) wanted to gauge the level of understanding, confidence and learning needs of cardiology professionals to better implement European Society of Cardiology (ESC) lipid lowering guidelines. Purpose The aim of the project was to highlight gaps in knowledge to better inform needs for training and educational programmes developed by ACNAP. Methods A 29 question electronic survey was developed by expert consensus, exploring previous experience, clinical knowledge, and perceptions of learning needs. It was launched at the EuroHeartCare conference in June 2023, on social media, and members of the ESC were emailed inviting participation. Results 123 people responded. 29.5% of the respondents were physicians and 70.5% NAPs. Most respondents were involved in lipid optimisation of some description with only 7.0% of respondents having no direct involvement in their patient cohort. A higher percentage of respondents responded "totally agree" when asked it they knew what cholesterol targets to aim for in secondary prevention, compared to primary prevention (61% v 41.5%). 94% of respondents felt comfortable when to initiate statins and and 82% ezetimibe. This reduced to 45% for inclisiran and 40% for bempedoic acid. Similarly, the majority felt comfortable counselling a patient newly initiated on statins or ezetimibe, but significantly fewer the newer lipid lowering therapies. Experience and understanding of familial hypercholesterolaemia (FH) was also explored. Only half the respondents would be comfortable in identifying and diagnosing FH and a further 25% unsure. A large percentage (37%) were unaware of the Simon Broome criteria or the Dutch Lipid Criteria Network (49%). When considering learning needs, 71% of NAP respondents needed extra support to help make lipid lowering decisions. This rises to 84% and 74% when looking at nurses and pharmacists separately, respectively. Nearly 76% would prefer any learning to be delivered online, with interactive online training packages being the most popular method. Conclusions The three main gaps identified by NAPs were: management in primary prevention (initiation and targets), the newer innovative medicines (bempedoic acid, inclisiran and PCSK9 monoclonal antibodies) and FH. Interestingly, these are the same gaps highlighted by physician responders. These findings can help guide ACNAP and ESC in the development of educational programmes with the aim to improve better lipid management overall.

"The medicine is not something that interests me at all." Beliefs, health-related behaviors, and medication adherence in patients with symptomatic peripheral arterial disease

Abstract Background Despite evidence-based guidelines recommending secondary prevention with antithrombotics and lipid-lowering therapies, adherence to optimal pharmacological therapies remains suboptimal in patients with symptomatic lower extremity peripheral arterial disease (PAD), potentially contributing to excess morbidity and mortality. However, the behavioral factors and health beliefs underlying this behavior are still poorly understood. Purpose To explore the health-related behaviors and beliefs of patients with symptomatic PAD regarding secondary preventive therapy. Methods Using a qualitative design, we conducted individual semi-structured interviews with patients diagnosed with symptomatic PAD. Participants were recruited from four departments of vascular surgery in Denmark from December 2022 to January 2024. Data analysis was performed using framework analysis based on the six domains of the Health Belief Models1 (HBM) as analytical framework: perceived susceptibility, severity, benefits, barriers, cues to action, and self-efficacy. The HBM is widely used for conceptualizing individual’s attitudes and beliefs to explain and predict health behaviours. Results Sixteen patients participated in the study: seven adherent and nine non-adherent patients. Based on the HBM components, the following findings emerged (Figure 1). Patients expressed low perceived awareness of the severity of PAD and its potential consequences, not recognizing PAD as a systemic condition associated with broader cardiovascular risk. The perception of PAD centered around the experience of excruciating leg pain and its impact on everyday life. This focus on symptoms affected the perceived benefits of secondary preventive therapies. Patients lacked knowledge about the importance and goal of treatment and did not link the secondary preventive therapy to PAD, often associating it only with other cardiovascular diseases. Barriers included inadequate understanding of the chronic progressive nature of PAD and its severity, experience and fear of side-effects, prescription confusion, pill burden, financial constraints, and allergies. Fear of recurring pain, complications, and early death served as strong internal adherence triggers. Paradoxically, despite expressing fear, some patients were only adherent to antithrombotic therapy, not assigning the same importance to statins. Other cues to action included practical arrangements as well as establishing a trusting patient-provider relationship and receiving comprehensive and logical explanations. Conclusions This study provided new perspectives on the multifaceted challenges hindering adherence to secondary preventive therapy among patients with symptomatic PAD. Notably, the insufficient knowledge regarding the chronic progressive nature of PAD and its cardiovascular implications, underscores the need for enhanced patient education and tailored interventions to ensure optimal secondary preventive therapy.Figure 1

Angioprotein-like 3 and atheroma progression in statin-treated type 2 diabetic patients with coronary artery disease: the pre-specified analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Despite guideline-recommended control of LDL-C with a statin, type 2 diabetic patients more likely cause cardiovascular events. This indicates the need to identify additional therapeutic targets in those patients. Angioprotein-like 3 (ANGPTL3) is an inhibitor of lipoprotein and endothelial lipase, which increases the levels of LDL-C and other atherogenic lipoproteins. These properties suggest ANGPTL3 as a potential driver associated with diabetic atherosclerosis. The OPTIMAL randomized controlled trial (jRCT1052180152) compared the efficacy of continuous glucose monitoring-guided versus HbA1c-guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic patients by using serial intravascular ultrasound (IVUS) imaging. This pre-specified analysis of the OPTIMAL study was designed to evaluate whether ANGPTL3 affects progression of coronary atheroma in statin-treated type 2 diabetic patients. Purpose To elucidate the association of serial change in ANGPTL3 with the degree of atheroma progression in statin-treated type 2 diabetic patients. Methods 59 patients (59 lesions) with serial ANGPTL3 levels at baseline and week 48 were included into the current analysis. Clinical demographics and IVUS-derived measure were compared in patients with and without any increase in ANGPTL3. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, any increase in ANGPTL3 levels at week 48 was observed in 52.5% of study participants. Patients with any increase in ANGPTL3 were more likely to have a history of hypertension (90.0% vs. 64.3%, p=0.02), whereas there was no significant difference in on-treatment LDL-C levels between the two groups (1.8 ± 0.4 vs. 1.6 ± 0.6 mmol/L, p=0.25) (Table). On IVUS imaging analysis, baseline percent atheroma volume (PAV) did not differ in those with and without any increase in ANGPTL3. However, patients with any increase in ANGPTL3 presented a greater progression of PAV (0.08 ± 0.28 vs. -0.74 ± 0.29, p=0.04). There was a trend toward a lower frequency of PAV regression in those exhibiting any increase in ANGPTL3 (48.4% vs. 57.1%), but this comparison did not meet statistical significance (p=0.50) (Figure). Multivariate analysis adjusting clinical characteristics demonstrated that any increase in ANGPTL3 level was not independently associated with PAV progression (β=0.16, 95%CI=-0.01 – 0.18, p=0.27). Conclusion Over 50% of statin-treated type 2 diabetic patients with coronary atherosclerosis showed any increase in ANGPTL3 levels at week 48. Serial IVUS imaging revealed that patients with any increase in ANGPTL3 more likely presented a greater atheroma progression. However, this relationship did not exist after adjusting clinical characteristics. Our findings suggest that ANGPTL3 may not be a pivotal driver associated with atheroma progression in statin-treated type 2 diabetic patients.

Sex differences in atherogenic lipid profile following acute coronary syndrome

Abstract Background Despite significant advancements in lipid-lowering therapy, the management of dyslipidemia remains challenging in patients with acute coronary syndrome (ACS). Significant differences are shown in lipid panels and management between different sexes following ACS. Objective To shed light on the alterations and characteristics of atherogenic lipoproteins and the characteristics of patients who achieve LDL-C targets after statin treatment, harnessing real-world data from electronic health records of patients with ACS after their discharge between sexes. Methods The data in the present study were derived from the iHeart program sponsored by the Chinese Cardiovascular Association. Eligible patients with a diagnosis of ACS from January 2014 to December 2021 during hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed the control of atherogenic lipid profiles between sexes. The primary outcome was the achievement of the LDL-C target, defined as LDL-C <1.8 mmol/L. A multivariable logistic regression model was used to assess the associations between patient characteristics and LDL-C achievement. Results Between 2012 and 2021, 4861 patients (1299 [26.7%] women) were hospitalised with a primary diagnosis of ACS (49.2% STEMI, 13.8% NSTEMI, and 33.8% UA). The mean age was 64.9 (12.4) years. In contrast to a higher proportion of AMI in men, more prevalence of UA was observed in women. Women had more cardiovascular comorbidities than men and were more likely to receive lipid-lowering therapies, blood pressure-lowering therapies, glucose-lowering therapies, and antiplatelet medications at discharge. In both men and women, TC, TG, LDL-C, ApoB, and non-HDL-C levels significantly decreased within 12 months (P<0.05). Women had less reduction in atherogenic lipid profile than men. The rate of LDL-C <1.8 mmol/L was similar between sexes (14.3% vs16.1%; P=0.136) at baseline, whereas within 12 months after discharge, women had a much lower achievement rate of LDL-C target than men (34.6% vs 45.6%; P<0.001). The risk factors for non-achievement of the LDL-C target in men were revascularisation, history of MI, atrial fibrillation, newly diagnosed MI, and high baseline LDL-C levels. For women, the risk factor was hypertension and diabetes. Conclusion Substantial sex disparities were observed in the management of atherogenic lipids. Despite a higher likelihood of receiving guideline-recommended medical therapy at discharge, women had poorer lipid control compared to men, especially among those with NSTEMI.

Effects of lipid-lowering therapies on lipoprotein(a) levels in patients with dyslipidemia: a systematic review and network meta-analysis of 64 randomised controlled trials

Abstract Background Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease. However, there has yet to be a drug approved specifically for lowering Lp(a). There is paucity of studies evaluating the use of current lipid-lowering agents, and their effects, if any, on Lp(a). Purpose We aimed to identify and compare the effects of lipid-lowering therapies on Lp(a) levels, cardiovascular and safety outcomes, in patients with dyslipidemia. Methods A systematic search was performed across four databases (PubMed, Embase, Scopus, Cochrane) for randomised controlled trials (RCTs) published from inception to 3 January 2023. The percentage change of serum Lp(a) levels, cardiovascular and safety outcomes were compared among statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin), fibrates, ezetimibe, niacin, PCSK9 inhibitors (alirocumab, evolocumab, bococizumab) and inclisiran, in patients with primary dyslipidemia. Frequentist network meta-analysis was performed to compare the treatment effects among different drug classes, stratified by use of background statin therapy. Results A total of 64 RCTs were included, comprising 55,256 patients. In patients on background statin therapy, PCSK9 inhibitors significantly lowered Lp(a) levels, compared with placebo (mean difference [MD] -26.8, 95% confidence intervals [95%CI] -30.8 to -22.7), ezetimibe (MD -21.6, 95%CI -31.4 to -11.8), fibrates (MD -19.4, 95%CI -37.4 to -1.5), and niacin (MD -13.8, 95%CI -25.6 to -2.1). PCSK9 inhibitors were associated with lower risk of major adverse cardiovascular events and similar risk of treatment-related adverse events than placebo. Comparing the PCSK9 inhibitors, evolocumab achieved greater Lp(a)-lowering than alirocumab in patients on background statin therapy (MD -11.4, 95%CI -18.6 to -4.1), including those with heterozygous familial hypercholesterolemia. Niacin also achieved 12.9% (95%CI 1.8 to 24.0) reduction in Lp(a) compared with placebo, but had a higher risk of treatment-related adverse effects than fibrates. Statin monotherapy did not affect Lp(a) levels, regardless of type or intensity of statin therapy. Ezetimibe and fibrate had no effect on Lp(a) levels. Conclusions PCSK9 inhibitors produced the greatest effect on Lp(a) levels, compared with other lipid-lowering therapies. Further studies into PCSK9 inhibitors are necessary to characterise their efficacy and safety specifically for Lp(a)-lowering, and elucidate the impact of Lp(a) reduction on cardiovascular risk.% change in Lp(a) levels

Real-world evaluation of a lipid transformation project in primary care settings

Abstract Background The National Health Service England Long-Term Plan (2019) highlights the need to optimise lipid management to reduce cardiovascular disease (CVD) risk. A collaborative project was funded between a local health service and an industry partner to review current practice and improve outcomes in a UK region through introduction of lipid management pathways, primary care education and patient-focused reviews to optimise lipid-lowering therapies among high-risk patient groups. Purpose The project aimed to increase prescribing of CVD risk reduction therapies such as high-intensity statins (HIST), escalation of therapy to achieve lipid-lowering treatment targets, to improve clinician knowledge and confidence in lipid management and provide benefits for local populations in reducing CVD risk. Methods Systematic patient searches across six Primary Care Networks (PCNs) prioritised high-risk patients for review. Community of Practice sessions were held to facilitate shared learning and problem-solving. A pragmatic, real-world evaluation was conducted to explore the impact of the new pathways and tools on prescribing outcomes and optimisation of lipid-lowering therapies. To examine the changes in HIST prescriptions, a statistical analysis of open-source prescribing data was undertaken between baseline (December 2021) and follow-up (December 2022) on over 39,000 eligible patient records. Qualitative interviews with clinicians from all participating PCNs and a thematic analysis of emerging themes was conducted in 2023. Results A paired sample t-test demonstrated a significant increase in the percentage of HIST prescribed, of the total number of statins prescribed, across the six PCNs between baseline and follow-up t(5) = -3.38, p = 0.01. Table 1 illustrates the changes at individual PCN level. Four of the six PCNs reached the National Institute for Health and Care Excellence minimum threshold of 65% target for HIST prescribing in statin prescriptions and three of these PCNs exceeded the optimal target of 75% HIST. An additional 600 patients were prescribed Ezetimibe (as therapy escalation or for statin intolerance). Through qualitative data, clinicians reported development of new skills and knowledge, leading to increased confidence in optimising lipid management with medication and lifestyle interventions. Conclusion The lipid transformation project demonstrated significant improvements in prescribing of lipid-lowering therapies and improved clinician competence in lipid management pathways and guidance. This has enabled sustainable improvements in lipid management and cardiovascular disease reduction in local populations.

Apolipoprotein B and the regression of lipidic plaque in statin-treated type 2 DM patients with coronary artery disease: the pre-specified sub-analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Type 2 diabetic mellitus (T2DM) patients more likely present vulnerable form of diseases. Despite lowering LDL-C level with a statin, their on-going cardiovascular risks still exist, which indicates the need to identify additional therapeutic targets in T2DM patients. Apolipoprotein B (ApoB) is a proatherogenic lipoprotein. Atherosclerosis is promoted via the influx of ApoB into vessel wall. The current ESC guideline recommends ApoB levels as a secondary therapeutic target under control of LDL-C levels with a statin. However, it remains to be fully determined about the association of ApoB levels with plaque vulnerability in statin-treated T2DM patients. Purpose To elucidate whether serial change in ApoB levels affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging. Methods The OPTIMAL randomized controlled trial compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in 94 statin-treated T2DM patients with CAD. Serial NIRS/IVUS imaging was conducted at baseline and week 48 to monitor non-culprit lesions. The current study included 71 patients with serial ApoB levels at both baseline and week 48. Clinical demographics and NIRS/IVUS-derived measures were compared in those with and without any reduction of ApoB levels. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, 60.6% of study subjects exhibited any reduction of ApoB levels, accompanied by a greater reduction of LDL-C levels. Patients with any reduction of ApoB levels were more likely to be older (67.4±10.0 vs. 71.7±7.3 years, p=0.03), whereas there were no significant differences in the proportion of established risk factors between the two groups. Baseline NIRS/IVUS-derived PAV (47.1±12.9 vs. 44.8±15.4%, p=0.54) and maxLCBI4mm [290.5 (205.5, 338.7) vs. 270.0 (97.0, 416.0), p=0.76] were comparable in patients with and without any reduction of ApoB. On serial NIRS/IVUS imaging analysis, the progression rate of atheroma volume did not differ between the two groups (-0.4±0.2 vs. -0.3±0.2mm3, p=0.77). However, patients with any reduction of ApoB more frequently presented a regression of maxLCBI4mm (27.6±0.1 vs. 61.5±0.1%, p=0.01). Multivariate analysis adjusting age, female and high-intensity statin use demonstrated change in ApoB as an independent factor associated with regression of maxLCBI4mm (OR=0.94, 95%CI=0.91-0.98, p=0.002). Conclusion In statin-treated T2DM patients with CAD, any reduction of ApoB levels was associated with a greater regression of NIRS-derived maxLCBI4mm. The current findings indicate a potential anti-atherosclerotic effect of lowering ApoB levels, which induces delipidation of diabetic coronary atheroma. ApoB may be an important therapeutic target to modulate lipidic plaque materials in T2DM patients receiving a statin.

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.

Burden of systemic inflammation and associated health outcomes in adults with atherosclerotic cardiovascular disease managed in routine care

Abstract Background The burden and outcomes of inflammation in people with atherosclerotic cardiovascular disease (ASCVD) are poorly defined, particularly beyond the controlled settings of trials and research cohorts. Methods We conducted a longitudinal observational study of adults with ASCVD undergoing C-reactive-protein (CRP) testing in routine healthcare in Stockholm, Sweden. After excluding CRP tests associated with acute illness and patients with medications/conditions that bias CRP interpretation, the systemic inflammation of participants was defined over a 3-month ascertainment window. Baseline determinants of CRP≥2 mg/L were explored with logistic regression, and baseline CRP categories were compared via Poisson and Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events (MACE), heart failure hospitalization, and all-cause death. Result After applying inclusion/exclusion criteria, we identified 84,399 adults with ASCVD with a mean age of 71 years and of which 54% were men. In total, 60% had CRP≥2 mg/L. At baseline, female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anemia, were associated with CRP≥2 mg/L. Conversely, the use of RASi, antiplatelets, and lipid-lowering therapy were associated with lower odds. Over a median follow-up of 6.4 years and compared to people with CRP <2 mg/L, those with CRP≥2 mg/L had a higher rate of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications during follow-up (P<0.05 for all). They also had a higher rate of MACE [adjusted hazard ratio (HR), 1.30; 95% CI, 1.27–1.33], heart failure hospitalization [1.24; 1.20–1.39], and all-cause death [1.35; 1.20–1.30]. Results were consistent across subgroups and more granular CRP categories, and robust to the exclusion of extreme CRP values or early events. Conclusions Two in three adults with ASCVD have systemic inflammation. A CRP≥2 mg/L is associated with excess healthcare resource utilization as well as increased rates of MACE, heart failure, and death.

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.

Lipoprotein(a) levels and cholesterol efflux capacity: inverse association and impact on atherosclerosis in familial hypercholesterolemia patients on lipid-lowering therapy

Abstract Backgrounds Familial hypercholesterolemia (FH) patients have higher serum lipoprotein(a) (Lp(a)) levels than non-FH patients, and high Lp(a) levels raise atherosclerotic cardiovascular disease (ASCVD) risk 1). We previously reported that decreased cholesterol efflux capacity (CEC) is a risk marker for ASCVD in patients with statin-treated FH 2). Others have reported that Lp(a) interferes with the enhancement of ABCA1-mediated cholesterol efflux by plasminogen and that ABCA1-mediated CEC is lower in patients with Lp(a) >50 mg/dL. However, the association of CEC, not necessarily ABCA1-mediated, with Lp(a) is not clear and has not been studied in patients with FH. It is also unclear whether high Lp(a) and low CEC in patients with FH are associated with the severity of atherosclerosis. Purpose We examined whether Lp(a) levels are negatively associated with ABCA1-independent CEC in patients with FH receiving lipid-lowering therapy. We also examined the impact of the combination of high Lp(a) and low CEC on the presence of corneal arcus, Achilles tendon thickness, carotid intima-media thickness (IMT), and pre-existing ASCVD. Methods This cross-sectional study included 371 patients clinically diagnosed with FH receiving lipid-lowering therapy. CEC was measured in apolipoprotein B-depleted plasma and 3H-cholesterol-labeled J774.1 cells without cAMP-stimulated ABCA1 overexpression. Lp(a) was measured by enzymatic methods (Sekisui Medical, Tokyo, Japan) using an automated analyser. Achilles tendon thickness was measured by X-ray and carotid IMT by ultrasound. Results Mean age was 55±16 years, and 191 (51%) were women. The median serum Lp(a) level was 18.7 mg/dL, higher than the previously reported median level (13 mg/dL) in a Japanese population. One hundred nineteen patients (32%) had serum Lp(a) levels of 30 mg/dL or higher, and they had significantly lower CEC (P=0.0015). This negative association persisted after adjusting for age, sex, BMI, smoking status, serum LDL-cholesterol, serum triglycerides, and eGFR in a multiple linear regression model (beta-coefficient: -0.047, 95% CI: -0.075 - -0.019, P=0.0011). In addition, patients with both Lp(a) > 30 mg/dL and CEC lower than the median had a higher percentage of corneal arcus, thicker Achilles tendons, greater carotid IMT, and a higher prevalence of pre-existing ASCVD compared to patients with either or neither. Conclusions We found an inverse relationship between Lp(a) levels and CEC in FH patients receiving lipid-lowering therapy. Our results suggest that Lp(a) may also inhibit ABCA1-independent CEC, including passive cholesterol diffusion from peripheral cells. Furthermore, the combination of high Lp(a) and low CEC may be a residual risk for patients with FH receiving lipid-lowering therapy. Future studies are needed to determine whether agents that decrease Lp(a) levels will increase CEC and thereby resolve part of the residual ASCVD risk in FH.

Prognostic values of lipoprotein(a) levels for secondary prevention of acute coronary syndrome among patients who underwent primary percutaneous coronary intervention

Abstract Background Lipoprotein(a) [Lp(a)] is known to be a residual risk factor for acute coronary syndrome(ACS). However, in the current era where primary percutaneous coronary intervention (PCI) and lipid-lowering therapies have advanced, the role of Lp(a) levels in secondary prevention among ACS patients remains unclear. Purpose The purpose of this study is to determine whether Lp(a) levels play a role in secondary prevention by studying patients with ACS who underwent primary PCI and survived discharge. Methods Consecutive ACS patients who were admitted to our institution between December 2016 and March 2021, requiring primary PCI and were discharged alive were enrolled for the current study (n = 471). Of these patients, those with the following circumstances were excluded: (1) multidisciplinary treatment such as mechanical ventilation management and percutaneous cardiopulmonary support (n = 74), (2) incomplete clinical data (n = 34), (3) ACS classified as other than type 1 in the universal definition (n = 6), and (4) unknown prognosis at 6 months after discharge (n = 8). A total of 349 consecutive patients were included in the current study. They were divided into two groups according to Lp(a) levels: Lower Lp(a) group (Lp(a) < 30 mg/dL, n = 277) and Higher Lp(a) group (Lp(a) ≥ 30 mg/dL, n = 72). The primary endpoints were major adverse cardiac events (MACEs), composite of all cause death, nonfatal myocardial infarction, nonfatal stroke and congestive heart failure requiring admission. Event-free survival curves were estimated using Kaplan-Meier method and log-rank test was used to detect statistically significant differences. In addition, influence of Lp(a) levels on MACE was examined using three cox regression analyses. Model 1 was adjusted for age, gender and body mass index, model 2 was adjusted for hypertension, diabetes and chronic kidney disease (CKD), model 3 was adjusted for old myocardial infarction (OMI), smoking and multivessel disease, respectively. Results The mean age was 67.0 ± 12.8 years, and 70.5% were male. The median serum Lp(a) levels of the entire population was 14 mg/dL (interquartile range, 7 to 26). There were no significant differences about baseline patient’s characteristics, laboratory findings, and medications at discharge including statin treatment. The MACE was observed in 15.5% of the Lower Lp(a) group and 20.8% of the Higher Lp(a) group (p=0.29). No difference was observed about MACE between the two groups (log-rank p=0.45). After adjusting for cardiovascular risk factors, Lp(a) levels were not associated with MACEs in all three models. However, in model 2 and model 3, CKD and OMI were associated with MACEs (hazard ratio 4.29, 95% confidence interval 2.17 to 8.46, p < 0.001, hazard ratio 3.02, 95% confidence interval 1.39 to 6.51, p = 0.005, respectively). Conclusions In the current era, Lp(a) levels are not associated with secondary prevention among ACS patients who underwent primary PCI.

High intensity statin-ezetimibe combination therapy reduces mortality in patients with ischaemic heart disease and elevated Lipoprotein(a)

Abstract Background Early and prompt reduction of low-density lipoprotein cholesterol concentrations (LDL-C) using combination lipid-lowering therapy (LLT) is recommended to lower cardiovascular risk in patients with ischaemic heart disease (IHD) and elevated LDL-C. Lowering LDL-C is also an important cardiovascular risk mitigation strategy in patients with elevated lipoprotein(a) [Lp(a)]. However, it is unknown if combination LLT reduces mortality in patients with elevated Lp(a). Aim To undertake an observational study to investigate the effect of combination LLT using high intensity statin with ezetimibe on cardiovascular outcomes in patients with and without elevated Lp(a). Methods Serum Lp(a) concentrations were measured in 520 consecutively recruited patients with IHD admitted to hospital, half of whom were admitted for acute myocardial infarction. Patients treated with high intensity statin and ezetimibe within the 1st year from admission to hospital (‘HI statin-ezetimibe group’, n=157) were compared with the rest of patients who had less intensive lipid lowering regimen (‘Others group’, n=363) for cardiovascular outcomes. Results During the 2-year follow-up period, 14.6%, 6.5%, and 53.1% of patients had all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) respectively. Median age was 63.5 years and 82.3% were male. Multivariable Cox regression showed that baseline Lp(a) ≥70 nmol/L was associated with increased risk of all-cause mortality (HR 1.97, 95% CI 1.20-3.22, P=0.007). Compared with a less intensive regimen, HI statin-ezetimibe was associated with reduced risk of all-cause mortality (HR 0.44 [0.21-0.89], P=0.023) and MACE (HR 0.71 [0.52-0.95], P=0.027), with no statistically significant effect on cardiovascular mortality (HR 0.43, P=0.142). Notably, the cardiovascular benefits of HI statin-ezetimibe were more pronounced in patients with elevated Lp(a); a greater reduction in risk of MACE was seen for patients with Lp(a) ≥70 nmol/L (HR 0.51, P=0.007) or Lp(a) ≥100 nmol/L (HR 0.36, P=0.009), and in all-cause mortality risk for those with Lp(a) ≥70 nmol/L (HR 0.24, P=0.025). Although LDL-C reduction >50% was associated with reduced risk of all-cause mortality (p=0.027), this could not fully explain the overall cardiovascular benefit of HI statin-ezetimibe use in patients with or without elevated Lp(a). Conclusion Intensification of lipid-lowering therapy with high-intensity statin and ezetimibe improves cardiovascular outcomes in patients at very high cardiovascular risk, particularly those with elevated Lp(a). Larger studies are required to confirm our findings that this cardiovascular benefit is partially independent of LDL-C lowering.

Efficacy and safety of inclisiran in real-world clinical practice. Results from the CHOLINET Registry

Abstract Background/Introduction Inclisiran has been recently introduced in clinical practice. Thus, efficacy and safety data from real-world settings are limited. Purpose Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry including 36 Italian centers, designed to assess efficacy, safety, adherence and persistence of inclisiran treatment, and clinician’s behavior on LLT in very high CV risk patients with atherosclerotic CV disease and/or familial hypercholesterolemia (FH). Methods From November 2022 through February 2024, the Cholinet registry enrolled patients receiving inclisiran according to standard clinical practice. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at subsequent follow-up. Results We enrolled 668 patients in treatment with inclisiran (15.1% with FH, 30.7% female, mean age 63 years), Data on follow-up at 3 months (booster time) were available for 495 of them. At the time of inclisiran first prescription median LDL-C was 102 mg/dl and reached 51 mg/dl at the time of 3 months observation (50% mean reduction, 51 mg/dl absolute median reduction). None of the 495 patients reaching 3 months follow up missed the reinjection dose administration. Of 668 patients enrolled, 553 patients (82.7%) were on LLT, of them 107 (19.3%) were on ezetimibe alone, 67 (12.1%) on statin alone and 379 (68.5%) on a statin and ezetimibe combination. Of the enrolled patients, 45 (6.7%) were previously treated with evolocumab and 34 (5%) with alirocumab. Among the patients evaluated at the 3-month follow-up, 307 patients (62%) achieved the LDL cholesterol target; of them, 450 (91%) were treated with inclisiran and statin±ezetimibe. Evaluating the distribution of the percentage reduction in LDL cholesterol values, a heterogeneity emerged that was partly explainable by the concomitant lipid-lowering therapy and partly by the previous exposure to PCSK9 inhibitors. Conclusions These preliminary data from the Cholinet Italian registry show that inclisiran effectively reduces (50%) LDL-C in real-world settings. The LDL-C target was achieved in 62% of patients; of them 91% were on lipid-lowering therapy, showing that combination therapy is necessary in most of these patients.

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

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.

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.

Arterial stiffness characterization of patients with different ACS-causing plaque morphologies quantified by optical coherence tomography

Abstract Background Optical coherence tomography (OCT) has refined acute coronary syndrome (ACS)-management by enabling in-depth characterization of culprit lesions. Differentiating between plaques with ruptured (RFC) and intact fibrous cap (IFC) has shaped clinical decision making. However, the systemic vascular changes associated with different plaque morphologies remain unexplored. Purpose To investigate arterial stiffness among different ACS-causing plaque morphologies (RFC vs. IFC) and its prognostic value post-ACS. Methods We conducted a secondary analysis of a prospective registry study, including patients who underwent OCT-characterization of the ACS-causing culprit lesion and received arterial stiffness assessment 90 days post-index event. The association between arterial stiffness parameters, such as pulse wave velocity (PWV), aortic pulse pressure (APP), heart rate-corrected augmentation index (AIx@75) and plaque morphologies was assessed using logistic regression, adjusted for age, sex, hypertension, presence of diabetes mellitus, smoking status, LDL-C and discharge medications (ACE-inhibitors/ARBs, beta blockers, calcium-channel blockers and diuretics). A multiparameter model additionally included intima-media-thickness and all arterial stiffness metrics. Cox regression, further adjusted for stroke history, prior percutaneous coronary intervention or stable coronary artery disease and Killip class, evaluated the link between arterial stiffness parameters and major adverse cardiovascular events plus (MACE+). Results In total, 110 patients with arterial stiffness and OCT data were included. Of these, 78 (70.9%) patients had RFC- and 32 (29.1%) IFC-ACS. The median age was 61.5 years and 80.0% of patients were male. Patients with RFC- had significantly higher PWV (8.35 vs. 7.50 m/s, p=0.015) compared to IFC-ACS. Both groups received similar regimens of antihypertensive, diuretic and lipid-lowering pharmacological therapy at discharge (p>0.1). After multivariable adjustment, increased PWV (4th Quartile [Q4] vs. 1st Quartile [Q1] Adjusted Hazard Ratio [aHR]: 1.38 [95% Confidence Interval (CI) 1.02-1.88], p=0.043) was associated with RFC- while high APP was significantly associated with IFC-ACS as the underlying plaque morphology (Q4 vs. Q1 aHR: 0.65 [95% CI 0.48-0.87], p=0.005) (Figure 1). Furthermore, per one-unit increment in APP we observed a 10% increase in risk for MACE+ in patients with RFC-ACS (aHR: 1.10 [95% CI 1.02-1.19], p=0.016) but not IFC-ACS (aHR: 0.95 [95% CI 0.82-1.11], p=0.54). No risk modification with increases in PWV and AIx@75 were observed, regardless of underlying plaque pathology (p>0.05). Conclusion There are distinct differences in arterial stiffness between patients with RFC- and IFC-ACS. These results underscore the value of a patient-specific approach that integrates invasive and non-invasive vascular characterization for identifying high-risk individuals and guiding therapy to enhance clinical outcomes.

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.