LDL-C Goal Research Articles

Lipoprotein (a) and long-term outcome in patients with peripheral artery disease undergoing revascularization

Background and aimsDespite low LDL-C goals, the residual risk for further cardiovascular (CV) events in patients with peripheral artery disease (PAD) remains high. Lipoprotein (a) (Lp(a)) is a known risk factor for PAD incidence, but little is known regarding the outcome in patients with symptomatic PAD. Thus, this study investigates Lp(a) and CV mortality in PAD after endovascular repair. MethodsA total of 1222 patients with PAD in two cohorts according to Lp(a) assay in nmol/L (n = 964, Lip-LEAD-A) or mg/dl (n = 258, Lip-LEAD-B) were followed up for 4.3 (IQR 3.0–5.6) or 7.6 (IQR 3.2–8.1) years. Lp(a) was measured before endovascular repair for either intermittent claudication (IC) or critical limb ischemia (CLI). Outcome information was obtained from the federal death registry. ResultsIn Lip-LEAD-A, 141 CV-deaths occurred (annual calculated CV-death rate 3.4%), whereas 64 CV-deaths were registered in Lip-LEAD-B (annual calculated CV-death rate 3.3%). After adjustment for traditional CV risk factors Lp(a) was neither associated with outcome in Lip-LEAD-A (highest tertile HR 1.47, 95%CI [0.96–2.24]) nor in Lip-LEAD-B (highest tertile HR 1.34 [0.70–2.58]). Subanalyses for IC (HR 1.37 [0.74–2.55]; HR 1.10 [0.44–2.80], CLI (HR 1.55 [0.86–2.80], HR 3.01 [0.99–9.10]), or concomitant coronary artery disease (CAD; HR 1.34 [0.71–2.54]; HR 1.21 [0.46–3.17]) failed to show a significant association between Lp(a) and CV-mortality. ConclusionsIn this large-scale cohort of symptomatic PAD no association of elevated Lp(a) with CV mortality was found over a median observation period of 5 years. Thus, an even longer study including asymptomatic patients is warranted.

Persistence to long-term PCSK9 inhibitors treatment and its effectiveness in familial hypercholesterolemia: data from the SAFEHEART study

Abstract Background Most patients with heterozygous familial hypercholesterolemia (FH) do not achieve current LDL-C goals proposed by European guidelines with conventional lipid-lowering therapy (LLT). Chronic use of PCSK9 inhibitors (PCSK9i) have shown to reduce LDL-C levels up to 61% on top of statins. Persistence to chronic LLT is important to reduce the burden of atherosclerotic cardiovascular disease (ASCVD). Purpose To analyze persistence and effectiveness of PCSK9i in clinical practice setting in FH patients from the SAFEHEART register with long-term follow-up. Methods SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of FH. Follow-up is carried out every year through a standardized phone-call to collect clinical conditions, persistence to medications, lipid profile, and cardiovascular events. This study analyses subjects ≥18 years of age on stable LLT who have received PCSK9i. Results 696 individuals (46% females), median age 56.4 years (IQR 49–66) started with PCSK9i (49% alirocumab and 51% evolocumab). Out of them 38% had history of ASCVD, and 89% were on maximum LLT. Median LDL-C at the moment of starting PCSK9i was 145 mg/dL (IQR, 123–177), representing a poor 2016 & 2019 ESC/EAS guidelines achievement (3% and 0.1% respectively). After a median follow-up of 3.7 years (IQR, 2.3–4.8), 669 patients (96%) remained on PCSK9i treatment during entire follow-up. Only 27 patients (4%) discontinued, 5 temporarily (0.7%) and 22 permanently (3.2%). Most common reasons for PCSK9i treatment interruption were medical decision (n=6), adverse event (AE) (n=5), patient decision not related with AE (n=5) and comorbidity (n=5). Median time to permanent discontinuation was 15 months (IQR, 4–33). Median LDL-C levels observed and % of LDL-C reduction obtained after 1 year of treatment and in the last follow-up visit were: 63 mg/dL (IQR, 43–88), 61 mg/dL (IQR, 44–82), 57.6% (IQR, 39.5–69) and 58% (IQR, 44–68), respectively. 2016 ESC/EAS guidelines LDL-C goals was achieved by 70% of patients at year 1 and 77% in the last follow-up visit after the introduction of PCSK9i (p<0.001). 2019 ESC/EAS goals were achieved by 44.5% and 48% (p=0.1). Conclusion Long-term persistence to PCSK9i treatment in FH patients is very high (96%) and reasons for discontinuation are diverse. This study shows that COVID-19 pandemic did not affected persistence to treatment. Effectiveness in LDL-C reduction and LDL-C goal achievement improved significantly with introduction of PCSK9i in clinical practice setting. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMGEN

Risk stratification and lipid evaluation in Mexican patients, evidence of lipid and cardiovascular analysis of a real world data registry (REMECAR)

Abstract Background and purpose Dyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aims to describe the baseline LDL-c levels of patients at cardiovascular clinics and evaluate the proportion of them who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines. Methods The REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP. Results A total of 5,443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid lowering treatment at entry, while 12.4% were receiving high intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9±40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70–50 mg/dL and 19.3% were achieving LDL-c levels <55mg/dL (Figure 1B) In diabetic patients at very high risk, only 25.7% reached their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals. Conclusions A significant number of patients were not receiving lipid lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimisation of lipid lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMGEN

Potential barriers in lipid-lowering treatment with PCSK9 inhibitors from a healthsystem perspective. Comparative evidence from ten countries

Abstract Background Gaps between clinical guidelines and attainment of LDL-C goals are evident across jurisdictions. Despite strong evidence of benefit from PCSK9-inhibitors (PCSK9i) treatment in eligible patients, significant underuse remains, suggesting considerable unmet need in clinical outcomes optimization. Purpose We investigated key performance endpoints across 10 countries to provide a comparative assessment of potential barriers in PCSK9i therapeutic integration from a healthcare system perspective. Methods We performed secondary analysis of peer-reviewed literature, health technology assessment reports, guidelines, clinical pathways since 2015 and constructed a comparative framework of pre-defined endpoints for 10 study countries (Japan, Italy, Spain, Australia, Canada, United Kingdom, Germany, France, Netherlands, USA). We identified 8 endpoints, which were clustered in 3 domains: (a) healthcare system characteristics, (b) demand-side policies, (c) medicine reimbursement policies, pertaining to cost-sharing. Approved PCSK9i indications were in scope. Results PCSK9i are reimbursed in all countries. Prescribing restrictions have been applied in all countries (Table 1). PCSK9i for primary prevention are reimbursed mainly in familial hypercholesterolemia, while additional criteria may apply depending on country and condition. PCSK9i are: (a) reserved mainly for very high- or high-risk cohorts (Japan, UK, Netherlands); (b) reimbursed for secondary prevention when additional risk factors/comorbidities exist (Australia, Germany, Netherlands); (c) recommended as 3rd line in 6 countries, as 2nd line in 3 and alone or in combination with other therapies in the USA; and (d) restricted to specialist prescribing while general practitioners cannot initiate treatment in 6 countries, potentially increasing waiting times and underuse rates. Follow-up periods may apply prior to establishing eligibility and vary from 3–12 months, while prior authorization/eligibility documentation may be necessary adding to administrative burden. Age criteria may apply in determining or continuing reimbursement (e.g. max 80 years in Italy). Regional and insurance plan variations apply in Canada and USA, respectively. LDL-C reimbursement thresholds are applied in 7 countries. Their relevance to guideline-recommended goals suggests potential underuse gaps (Fig. 1). While no threshold applies in Germany, an additional criterion of indication for LDL-apheresis determines eligibility. Cost-sharing ranges between 0–30% in co-insurance models, may include a flat fee, a deductible or combination of these. Conclusion Restrictions in the use of PCSK9i from marketing authorization labels are implemented in all 10 countries and differ across key endpoints. Significant differences exist between guideline-recommended LDL-C goals and reimbursement thresholds, while additional prescribing and documentation restrictions apply over reimbursed indications, contributing to potential underuse. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen Inc.

Simulation of bempedoic acid in the lipid-lowering treatment pathway using the European contemporary SANTORINI cohort of high- and very high-risk patients

Abstract Background Lowering LDL-C treatment goals in the 2019 ESC/EAS guidelines necessitates greater use of combination therapies (1). Cost of PCSK9 inhibitors (PCSK9i) and efficacy of ezetimibe alone as add on therapies limit population level achievement of LDL-C goals. Purpose This simulation study assessed the addition of oral bempedoic acid (BA) to ezetimibe in the treatment pathway in a real-world cohort of patients in order to assess the proportion of patients who might reach goal. Methods SANTORINI is a cohort study of European patients at high or very-high CV risk. Patients who were receiving any known LLT regimen with available data on LDL-C at baseline were eligible for this analysis. For patients not at risk-based LDL-C goals, the following treatment algorithm was applied (Figure 1), first the addition of ezetimibe and subsequently BA for those on statins, or addition of BA for those on ezetimibe and not at goal. Patients on PCSK9i remained in the cohort but no simulation was done. LDL-C reductions associated with ezetimibe and BA treatment were based on probabilistic distributions sourced from clinical trial efficacies based on prior studies (2–3). The effect of treatment on LDL-C levels was simulated through a Monte Carlo simulation run 10,000 times. No statin intensification was simulated as we assumed statin therapy was at maximum tolerated dose. Results At baseline (N=6252), mean age was 66 years and mean baseline LDL-C was 80.6 mg/dL with 1444 patients (23%) at goal; 93% (n=5797) were very high risk and 7% (n=455) high risk, of whom 84% (n=5227) were on statins, 23% (n=1447) on ezetimibe and 9% (n=546) on PCSK9i. Out of 4486 patients entering the simulation, 3419 received ezetimibe add-on with a third of those predicted to be achieving their risk-based goal (32%, n=1078/3419). Of those on ezetimibe and not at goal, the addition of BA would be predicted to result in another 36% goal achievement (n=1218/3408). Overall, the number of patients at goal would be expected to increase from 1444 (23%) at baseline to 2522 (40%) and 3740 (60%) after addition of ezetimibe and BA, sequentially. The mean LDL-C for the whole cohort would be expected to fall through this pathway from 80.6 mg/dL at baseline to 69.2 mg/dL and 61.1 mg/dL, respectively. Conclusion Few patients in the SANTORINI cohort were at goal at baseline and few would have LDL-C eligible for PCSK9i use. Optimising use of ezetimibe and BA after statins in the ESC/EAS 2019 LLT pathway could result in significantly more patients attaining lipid goals with likely additional health benefits. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

High individual variability in LDL-reductions after inclisiran administration in a “real-world setting”

Abstract Background and aims Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9) (1). Previous studies suggest that inclisiran provides sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. Patients included in the ORION program received inclisiran on top of maximally tolerated statin therapy and demonstrated a profound 50% LDL-C reduction as early as 3 months (2). The aim of this retrospective, multi-center analysis was to use individual patient data to determine the extent of the variability in LDL-C reduction in response to inclisiran administration in a real-world setting. Methods Since February 2021 the German Inclisiran Network (GIN) enrolled patients who received inclisiran due elevated LDL-cholesterol (LDL-C) levels in German lipid clinics. In contrast to patients included in the ORION program inclisiran could be administered to a broad range of patients with elevated LDL-C levels, including patients naive of lipid-lowering drugs, as well as patients on apheresis who failed to attain LDL-C goals. Results In 10 lipid clinics in Germany a total of 117 consecutive patients received inclisiran. Patients, who were not on stable lipid-lowering medication at least 3 months prior to inclisiran administration, were excluded. Thus, a total of 61 patients were analyzed. Mean LDL-C level at baseline was 151.86±64.31 mg/dl (95 percent confidence interval (CI): 135.39 to 168.33 mg/dl). After 3 months, inclisiran reduced LDL-C levels by 34.6% (95% CI: 29.3 to 39.8%), mean LDL-C levels were 103.26±60.36 mg/dl (95% CI: 87.8 to 118.72 mg/dl). At baseline 18 (30%) patients received statins, 22 (36%) ezetimibe and 13 (21%) bempedoic acid. Twenty-five (41%) patients were not on any lipid lowering therapy at baseline and 15 (25%) were on apheresis and failed to attain LDL-C target levels at baseline. Altogether there was a high inter-individual variability in LDL-C reduction 3 months after the first administration of inclisiran (Figure 1). Interestingly, patients who received statins at baseline demonstrated a trend towards a more profound LDL-C reduction (42.6±20.6 vs. 30.33±19.2%). This effect, however, was not significant. Two patients did not demonstrate any LDL-C reduction after the first administration. Inclisiran was well tolerated. Only one patient reported a minor injection-site reaction. No further side-effects were reported. Conclusion These results indicate that there is substantial individual variability in the LDL-C reduction after the first administration of inclisiran. Inclisiran was well tolerated without any serious side-effects. A longer follow-up period and further research is warranted to elucidate reasons for the high inter-individual variability in LDL-reductions in this real-world setting. Funding Acknowledgement Type of funding sources: None.

Jena auf Ziel: get all patients with ST-elevation myocardial infarction on EAS/ESC-LDL-C targets

Abstract Background and aims Low-density lipoprotein cholesterol (LDL-C) reduction is an essential part of the 2019 ESC/EAS dyslipidemia guidelines [1]. Only 18% of patients achieve 2019 ESC/EAS LDL-C target goal in secondary prevention [2]. “Jena auf Ziel – JaZ” (“Jena on target”) is a prospective study that aims at LDL-C target attainment in all patients with ST-elevation myocardial infarction (STEMI) and determination of reasons for failed target attainment. Methods All STEMI patients were started on atorvastatin 80 mg/ezetimibe 10 mg on admission. LDL-C levels were monitored during the hospital stay and a 12 months follow-up period. Patients were educated about cardiovascular risk factor optimization. Individual patient cards to document LDL-C levels over time were used to enforce LDL-C target attainment. Results In the first 50 consecutive patients, LDL-C levels were 3.39±1.23 mmol/L on admission, 1.84±0.86 mmol/L on discharge and 1.30±0.65 mmol/L during the first follow-up visit (6–8 weeks). On atorvastatin 80 mg/ezetimibe 10 mg 14 out of 50 patients (28%) reached the LDL-C goal on discharge, 36 out of 50 patients (72%) after 6–8 weeks. After addition of bempedoic acid or PCSK9-inhibitors all patients which were followed up in our lipid clinic reach the EAS/ESC-LDL-C target. Only two patients reported myalgias of which one patient refused to continue with lipid-lowering drugs. One patient had elevated liver enzymes, which resolved after switching to a lower statin dose. Conclusions One out three STEMI patients reached the EAS/ESC-LDL-C target during the initial hospital stay on atorvastatin 80 mg/ezetimibe 10 mg. Adding bempedoic acid or PCSK9 inhibitors resulted in LDL-C target attainment of all patients during follow-up. EAS/ESC-LDL-C target attainment is feasible and well-tolerated in empowered, well-educated patients. Funding Acknowledgement Type of funding sources: None.

Evolocumab treatment is associated with early and sustained reductions in low-density cholesterol (LDL-C) over 30 months: final results from the pan-European observational HEYMANS registry

Abstract Background Variability in LDL-C control at a population level associates with worse CV outcomes. This could in part be related to variations in patient adherence to self-administration regimens or variability in the response to a given therapy. Potent therapies such as PCSK9 inhibitors (PCSK9i) reduce cardiovascular events but some have questioned whether these therapies, which require dosing every 2 weeks, can offer sustained population level control of LDL-C. Purpose Using data from the HEYMANS registry, the objective of these analyses was to evaluate, at a population level, various metrics of variability in LDL-C reduction over time with evolocumab treatment. Methods HEYMANS was a prospective registry including adults initiating evolocumab treatment in clinical practice in 12 European countries between August 2015 to June 2020. Patient data were collected for ≤6 months before evolocumab initiation (baseline) and ≤30 months post initiation. LDL-C measurements were collected per clinical practice. At each 3-month time point in the study, we analysed median (and 95% CI) reductions in LDL-C, and the proportion of patients achieving ≥30% and ≥50% reductions in LDL-C from baseline. Results Data from 1951 patients were included in this final analysis (62% male, mean age 60 years, median baseline LDL-C 3.98 [Q1–Q3 3.17–5.07]) mmol/L). Most patients (85%) were receiving evolocumab for secondary prevention, with 40% not on oral LLT of whom the majority reported a history of statin intolerance. There was a median of 4 (Q1, Q3: 2, 6) LDL-C measurements per patient during follow-up. Within 3 months of initiating evolocumab treatment, LDL-C levels had reduced by a median of 58% and this reduction was maintained over 30 months (Figure 1). Among patients with an LDL-C value, ∼85% achieved a ≥30% reduction at each follow-up throughout the study, and ∼63% achieved a ≥50% reduction at each visit (Figure 2). Conclusions In European clinical practice, evolocumab treatment was associated with early and sustained reductions in LDL-C of over 30 months, with limited variability in LDL-C reductions at a population level. Within 3 months of treatment, evolocumab was associated with ∼58% reduction in LDL-C levels that was maintained throughout the study. These data should reassure the clinical community that meaningful, consistent additional reductions in LDL-C can be achieved with use of evolocumab. As greater use of combination therapies is required to achieve lower LDL-C goals, expanding the use of PCSK9i could provide improvements in population level control of LDL-C in European clinical practice. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen (Europe) GmbH

A Multicenter, Randomized, Double-blind, Active-controlled, Factorial Design, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia

Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia. Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups. Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. gov identifier: NCT04584736.

The beneficial effect of a comprehensive diabetes care model on high-risk relatives accompanying patients with type 2 diabetes

AimsAssess the effect of a diabetes program on lifestyle, metabolic, and mental health parameters in relatives of patients with T2D, and correlate changes between relatives and patients. MethodsRelatives were included in a structured program for patients with T2D. They received individualized interventions or were asked to follow lifestyle modifications indicated to their patient with diabetes. Outcomes were change in BMI, fat loss, patients achieving LDL-c and triglycerides goals, exercise, and mental health indicators at three and twelve months. ResultsWe included 200 relatives. Obesity was present in 42 %, hypertension in 8.5 %, hypercholesterolemia in 29.5 %, and hypertriglyceridemia in 46 % of relatives. Relatives lost − 3.7 kg and − 3.0 kg of body fat at three months and one-year evaluations. At least 60 % achieved normal triglycerides and LDL-c, and 40 % exercised at least 150 min/week. Anxiety symptoms dropped from 37 % to 22 % (p = 0.001), and depressive symptoms from 22 % to 12.9 % (p = 0.01) at three months. Correlations were found between the changes in relatives and patients in weight at three months (r = 0.22, p = 0.001), one year (r = 0.3, p < 0.001), and the number of goals achieved at one year. ConclusionRelatives of patients with diabetes attending a multidisciplinary program for T2D benefit in metabolic, lifestyle, and mental health indicators.

Evaluating Statin Tolerability in Historically Intolerant Patients After Correcting for Subclinical Hypothyroidism and Vitamin D Insufficiency.

Atherosclerotic cardiovascular disease (ASCVD) is the major cause of morbidity and mortality worldwide. Statins provide primary and secondary ASCVD prevention. Intolerance due to statin-associated myalgias reduces long-term adherence, thus muting potential benefits. Our analysis sought to determine whether transition from a lipophilic statin to a water-soluble statin, or correction of subclinical hypothyroidism and/or vitamin D insufficiency/deficiency (metabolic abnormalities), improved statin tolerance. We performed a retrospective analysis of the data from patients referred to our lipid clinic because of statin intolerance. Patients intolerant to a lipophilic statin were switched to a water-soluble statin. Patients having vitamin D insufficiency/deficiency or subclinical hypothyroidism were re-challenged with a water-soluble statin (or lipophilic statin with minimal systemic exposure) after correction of the metabolic abnormality. 169 patients were statin intolerant. 86% (n = 145) were white and 48% (n = 81) were male. 82 of these patients had one or both metabolic abnormalities. The remaining patients (n = 87) had no metabolic abnormality, however, were unable to tolerate a lipophilic statin. 72% (n = 73) of eligible patients (n = 101), defined as those with a corrected metabolic abnormality or without a metabolic abnormality on a lipophilic statin, were able to tolerate a water-soluble statin or lipophilic statin with minimal systemic exposure. In addition, 75% (n = 127) of this total cohort met their LDL-C goal. Our findings suggest that either correction of subclinical hypothyroidism and/or vitamin D insufficiency/deficiency or transition from a lipophilic statin to water-soluble statin (or lipophilic statin with minimal systemic exposure) improves statin tolerance.

Risk stratification and lipid evaluation in mexican patients, evidence of lipid and cardiovascular analysis in REMECAR. The mexican registry of cardiovascular diseases (REMECAR group)

Background and aimsDyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aimed to describe the baseline LDL-c levels of patients presenting to cardiovascular clinics and evaluate the proportion who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines. MethodsThe REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP. ResultsA total of 5443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid-lowering treatment at entry, while 12.4% were receiving high-intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9 ± 40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70–55 mg/dL and 19.3% were achieving LDL-c levels <55 mg/dL. In diabetic patients at very high risk, only 25.7% achieved their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals. ConclusionsAn important number of patients were not receiving any lipid-lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimization of lipid-lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk.

Effect of 1PC111, a Fixed-dose Combination of Pitavastatin and Ezetimibe, Versus Pitavastatin or Ezetimibe Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia or Mixed Dyslipidemia: A Randomized, Double-blind, Multicenter, Phase III Study

This study aimed to show that the efficacy of 1PC111 is superior to that of either ezetimibe or pitavastatin alone (monotherapy) for the treatment of hypercholesterolemia. This was a multicenter, randomized, double-blind, Phase III study. Patients with hypercholesterolemia or mixed dyslipidemia were randomized to receive 1PC111 (which was a fixed-dose combination of pitavastatin 2 mg and ezetimibe 10 mg), pitavastatin 2 mg, or ezetimibe 10 mg daily for 12 weeks. The primary end point was the difference in the percent change in LDL-C from baseline to week 12 between the 1PC111 and each monotherapy group. The secondary end points were the percent change in other lipid profiles from baseline to each visit. All patients were assessed for adverse events until end of study. A total of 388 patients were randomly assigned to the 1PC111 (n=128), pitavastatin (n=132), or ezetimibe (n=128) group. Generally, baseline characteristics were similar among the 3 groups. A statistically significant decrease in the LDL-C level at week 12 was observed in the 1PC111 group (-50.50% [14.9%]) compared with either the pitavastatin (-36.11% [11.4%]; P < 0.001) or ezetimibe (-19.85% [12.4%]; P < 0.001) group. Also, there was a statistically significant difference between 1PC111 and each monotherapy group in the reduction in total cholesterol, non-HDL-C, and apolipoprotein B levels. Moreover, there was a trend toward more efficient lowering of LDL-C levels in elderly patients (age ≥65 years) than in younger patients (age <65 years) by 1PC111 treatment. In patients given a class I recommendation for atherosclerotic cardiovascular disease prevention, the percentage of patients achieving the LDL-C target of <100 mg/dL at week 12 was significantly higher in the 1PC111 group than in both monotherapy groups (P < 0.001). Overall, the incidence of adverse events was similar among 3 groups. 1PC111 was more effective in improving lipid profiles and achieving the LDL-C goal than pitavastatin or ezetimibe alone for hypercholesterolemia treatment. Furthermore, 1PC111 may provide more benefit in treating elderly patients. gov identifier: NCT04643093.

LDL-cholesterol goal attainment through optimal implementation of the 2019 ESC/EAS dyslipidemia treatment algorithm in European patients with/without atherosclerotic cardiovascular disease: Simulation study from DA VINCI

Background and Aims : In the European-wide DA VINCI study, only 33% of patients attained their risk-based 2019 ESC/EAS guideline LDL-C goals. We aimed to simulate the impact of the step-wise implementation of the ESC/EAS lipid-lowering treatment (LLT) pathway on LDL-C goal attainment across risk categories.

Obicetrapib lowers LDL-C in patients on high intensity statins: Results from the rose trial (NCT04753606)

Background and Aims : As guidelines now recommend lower LDL-C goals, means that many patients require additional lipid lowering therapies (LLT) to attain risk based LDL-C goals despite use of high intensity statins (HIS). Cost and/or efficacy of current LLT options have limited their uptake in clinical practice. Mendelian randomization and RCT trial data support CETP inhibition as a validated target to reduce LDL-C and cardiovascular risk. Safety and efficacy concerns have to date limited the development of CETPi.

Achieving the LDL-C goal in Indian patients of acute coronary syndrome with high intensity statin

Background and Aims : High dose statin therapy is recommended to achieve the LDL-C goal<55mg/dL or >50% reduction from baseline. The aim of this pilot study is to investigate the time taken for achieving the LDL-C goal <55mg/dL and the proportion of ACS patients who could achieve the LDL-C goal with high intensity statins.

Management of secondary prevention patients with LDL-cholesterol levels &lt; 70mg/dl (1.8mmol/l): An analysis based on Delphi panel approach

Background and Aims : Current guidelines recommend at least 50% LDL-C reduction from baseline levels in patients with atherosclerotic cardiovascular disease in addition to getting the LDL-C goal of <55 mg/dL. We sought to determine how secondary prevention patients with LDL-C levels <70 mg/dL (1.8 mmol/L) are managed.

The change of LDL-C and treatment patterns among documented CAD/MI patients who underwent CAG in Taiwan: A retrospective cohort study

Background and Aims : Limited studies using electronic medical records describe LDL-C goal attainment after coronary artery disease/myocardial infarction (CAD/MI). We aimed to describe changes in LDL-C and treatment patterns after a documented CAD/MI by coronary angiography (CAG) in a medical center in Taiwan.

Efficacy and safety of evolocumab in chinese patients with primary hypercholesterolemia and mixed dyslipidemia: primary results of the Hua Tuo _ clinical trial

Background and Aims : The prevalence of dyslipidemia in China is approximately 40%, and many patients treated with lipid-lowering therapies fail to achieve LDL-C goals. This study evaluated the effect of evolocumab on LDL-C levels in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia with baseline LDL-C levels of ≥80 mg/dL or ≥130 mg/dL despite optimal stable statin therapy.

GOULD EDU: Primary Results of a Cluster-Randomized Trial of an Educational Intervention to Improve Guideline Adherence and Intensification of Lipid-Lowering Therapy

Lead Author's Financial Disclosures Research grants from AstraZeneca, Boehringer Ingelheim; other research support from AstraZeneca; consulting/advisory boards for Alnylam, Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, and Vifor Pharma; honoraria from Astra Zeneca, Boehringer Ingelheim, and Novo Nordisk. Study Funding Amgen. Background/Synopsis Despite the benefits of intensive LDL-C lowering in patients with ASCVD, guidelines supporting lower LDL-C goals, and improved access to therapies, implementation in clinical practice remains suboptimal, and strategies to improve guideline adherence are a priority. Objective/Purpose The GOULD EDU study tested the effectiveness of an educational intervention to improve intensification of LLT, LDL-C levels, and LDL-C goal achievement. Methods GOULD was a 2-year, prospective, observational registry in patients with ASCVD on any lipid-lowering therapy (LLT). In the GOULD EDU 1-year extension study, sites were randomized to early (STEP 1) or late (STEP 2) intervention in a stepped-wedge design. The educational intervention included 2 live webinars that reviewed recent LLT guidelines, patterns of LLT and LDL-C control in the US, and opportunities for improvement. In addition, all sites received site-specific, interactive reports of their LLT patterns that were updated throughout the study. Results 56 sites were randomized to STEP 1 (30 sites, 616 patients) or STEP 2 (26 sites, 382 patients). Across all sites, minimal change occurred in LLT during the study (Figure 1). Intervention STEPs 1 and 2 showed similar patterns of minimal LLT intensification and LDL-C change from baseline (BL). Of patients with available LDL-C data (BL: 518/998; study end: 639/998), 38.8% of patients had LDL-C <70 mg/dL at BL, and 36.9% (STEP 1) and 44.5% (STEP 2) had LDL-C <70 mg/dL at study end. Conclusions An educational intervention was not effective in improving LLT intensification, LDL-C levels, or attainment of LDL-C goals in patients with ASCVD. Education alone appears insufficient to improve guideline adherence. Research grants from AstraZeneca, Boehringer Ingelheim; other research support from AstraZeneca; consulting/advisory boards for Alnylam, Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, and Vifor Pharma; honoraria from Astra Zeneca, Boehringer Ingelheim, and Novo Nordisk.