Low-density Lipoprotein Cholesterol Goal Achievement Research Articles

Abstract 4131775: Effectiveness of Lipid-lowering therapy with Bempedoic Acid plus Ezetimibe in a Real-world Cohort

Introduction: Bempedoic acid and the combination with ezetimibe (BA+EZE) have demonstrated low-density lipoprotein cholesterol (LDL-C) lowering in clinical trials of adults with primary hyperlipidemia at high risk for or with cardiovascular disease. The impact of BA+EZE on LDL-C outcomes in a real-world cohort has not been studied. Aim: To evaluate the effectiveness of BA+EZE on LDL-C reduction and goal achievement using real-world data. Methods: This was a retrospective cohort study using deidentified electronic health records and linked claims data. Adult patients were included if they had a pharmacy claim for BA+EZE from March 1, 2020 to March 15, 2024 (date of first pharmacy claim = index date ), had ≥1 baseline LDL-C lab result on or within 6 months prior to the index date, and ≥2 LDL-C lab results post-index, including 1 lab result 12 months post-index (±60 days). Patients with documented use of ezetimibe on or within 6 weeks prior to index were excluded. For all patients with available valid lab results, LDL-C was determined at baseline (the value closest to but not after the index date), 3 months (±30 days), 6 months (±60 days) and 12 months (±60 days). Results: A total of 615 BA+EZE patients were identified (mean age 62±11 years, 52% women). At baseline, 64% had evidence of statin use in the prior 12 months and the mean LDL-C was 131±52 mg/dl. Figure 1 shows the change in the proportion of patients achieving LDL-C control at index, 3-, 6-, and 12-months post-index. The proportion of patients achieving LDL-C <100 mg/dL more than doubled from index (30%) to 3 months (67%), and was sustained through 12 months (55%). At 12 months, there were fewer patients with LDL-C ≥130 mg/dL (24% vs 47% at index). The mean LDL-C reduction was 28% at 3 months (to 94±47 mg/dL), 27% at 6 months (96±44 mg/dL), and 22% at 12 months (102±47 mg/dL) (p<0.0001 for all vs index). Conclusion: Patients who initiated BA+EZE showed early and sustained improvements in LDL-C. Future research should consider the impact of time on therapy and adherence on LDL-C control.

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

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

Lipid goal attainment across baseline socioeconomic and clinical factors comparing an "inclisiran first" implementation strategy and usual care: subgroup analysis of VICTORION-INITIATE

Abstract Background Addressing inequities in cardiovascular care has become a public health priority. Recent results from VICTORION-INITIATE, a pragmatically designed, randomised clinical trial showed the benefit of using inclisiran immediately if patients with atherosclerotic cardiovascular disease (ASCVD) fail to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL (1.8 mmol/L) on maximally tolerated statins. Purpose To evaluate effectiveness and safety of an "inclisiran first" implementation strategy (IF) versus usual care (UC) in subgroups that may be associated with healthcare inequities. Methods VICTORION-INITIATE was conducted at 45 representative clinical settings across 20 states in the USA. Patients with ASCVD randomised 1:1 (stratified by insurance status) received open-label inclisiran 284 mg at Days 0, 90 and 270) plus UC or UC alone (lipid management directed by treating physicians). Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per lipid guidelines. We compared efficacy and safety endpoints for IF and UC in prespecified subgroups (race, ethnicity, sex, renal function and statin intensity) and by income level (post-hoc analysis). Results The study randomised 450 patients. Baseline demographic and clinical parameters were balanced between study arms (≥65 years of age: IF: 63.1%, UC: 61.3%; non-White: IF: 15.6%, UC: 15.1%; Hispanic: IF: 13.8%, UC: 16.9%; female: IF: 29.8%, UC: 32.0%; income ≤$50,000: IF: 58.7%, UC: 58.2%; estimated glomerular filtration rate ≥30 to <60 mL/min/1.73m2: IF: 20.0%, UC: 17.8%; no statins at baseline: IF: 9.8%; UC: 10.2%). Across all subgroups, more patients achieved LDL-C goals at Day 330 with IF vs UC (Figure 1). Within the UC arm, the proportions of patients achieving LDL-C <70 mg/dL and <55 mg/dL, respectively, were numerically lower for non-White (8.8% and 2.9%) and Hispanic (10.5% and 2.6%) than White (24.6% and 10.2%) and non-Hispanic (24.9% and 10.3%) patients. We did not observe differences in LDL-C goal attainment for these subgroups in patients receiving IF. Compared with UC, IF resulted in greater mean percentage change in other lipids and lipoproteins from baseline to Day 330, irrespective of subgroup (Figure 2). Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively). Conclusions VICTORION-INITIATE enrolled a diverse population reflective of "real-world" US clinical practice. The IF strategy consistently resulted in higher rates of LDL-C goal attainment for all subgroups studied and did not lead to differences in lipid outcomes by race or ethnicity as compared to usual care. No additional safety concerns for the IF strategy were identified.

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

Low-density lipoprotein cholesterol goal attainment with "inclisiran first" versus usual care in patients with atherosclerotic cardiovascular disease

Abstract Background Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran administered twice-yearly by a healthcare professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC). Purpose To evaluate cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of participants (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an "inclisiran first" implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL [1.8 mmol/L] with maximally tolerated statins) compared with UC. Methods VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomised participants 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (<1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance status. Cumulative LDL-C exposure over time in the overall population and safety by subgroup were also evaluated. Results Of 450 patients randomised to IF or UC, 11.1% and 84.2% had an ASCVD event <1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was lower in patients treated with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, Figure). Significantly more patients who received IF achieved LDL-C goals of <70 mg/dL and <55 mg/dL at Day 330 vs UC, irrespective of subgroup (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6−71.2%, UC: 46.2−66.0% and IF: 10.7−28.3%, UC: 11.4−22.2%, respectively). Conclusions Participants with ASCVD and LDL-C >70 mg/dL who received IF had lower cumulative LDL-C exposure over the study period than those treated with UC. IF resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing and statin intolerance. The safety profile of IF was consistent across the subgroups analysed.

Recent trends of low-density lipoprotein cholesterol control and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Taiwan: 2015–2020

ObjectiveThis study aimd to assess recent trends in the control of low-density lipoprotein cholesterol (LDL-C) and the utilization of lipid-lowering drugs (LLD) among patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. MethodsPatients with ASCVD and without a history of hemorrhagic stroke were identified from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. ASCVD patients were stratified into four categories: those who ever had acute coronary syndrome (ACS), those who underwent percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG) without ACS, those who ever had an ischemic stroke (IS) without ACS or PCI/CABG, and other ASCVD cases. We assessed their latest recorded LDL-C levels for the periods 2015–16, 2017–18, and 2019–20. LLD therapy patterns were presented as monotherapy, dual therapy, or combination therapy of three or more drugs, with statin use classified by intensity. ResultsWe identified 3831 ASCVD patients in 2015–16, 3531 in 2017–18, and 1231 in 2019–20. LLD utilization rose from 58.4% in 2015–16 to 73.2% in 2019–20. The proportions of patients achieving LDL-C goals in 2015–16, 2017–18, and 2019–20 were 21.5%, 25.8%, and 33.3% in the ACS cohort (goal <70 mg/dL); 20.4%, 26.1%, and 39.0% in the PCI/CABG cohort (goal <70 mg/dL); 54.4%, 58.5%, and 58.9% in the IS cohort (goal <100 mg/dL); and 60.0%, 65.5%, and 67.0% in the other ASCVD cohort (goal <100 mg/dL), respectively. Over half of the patients were prescribed moderate-intensity statins. Statin use, age, history of diabetes mellitus, and hypertension were important factors for attaining LDL-C goal in ACS patients. ConclusionDespite improvements in LDL-C management observed over recent years, significant gaps remain in guideline adherence, especially for patients with ACS or PCI/CABG in Taiwan, with over 60% not meeting LDL-C targets. Intensifying efforts to align clinical practice with guidelines are imperative.

Real-World Application of Evolocumab Among Patients with Hyperlipidemia in Korea: A Multicenter Prospective Study.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major residual risk factor among patients with acute coronary syndrome (ACS). In the absence of sufficient real-world evidence, this observational (noninterventional) study investigated the effectiveness and safety of evolocumab in patients with hyperlipidemia treated with evolocumab for ACS in a real-world clinical setting in Korea. Between January 2022 and February 2023, patients from 10hospitals in Korea who initiated evolocumab within 24weeks of an ACS event were enrolled. Data collected at visit1 (evolocumab initiation) included patients' characteristics, comorbidities, and lipid-lowering therapies. LDL-C reduction from visit1 (week0) to visit2 (week8) was assessed. The primary outcome was the proportion of patients who achieved LDL-C < 1.4mmol/L (55mg/dL) at follow-up; the secondary outcome was the proportion who achieved LDL-C < 1.8mmol/L (70mg/dL) at follow-up. In this study, 89 out of 142 enrolled patients were included in the effectiveness analysis. The mean (SD) age of the included patients was 59.3 (12.3) years, with the majority being male (87.6%). Sixty-one patients received statin-ezetimibe combination therapy (68.5%). The median [Q1, Q3] LDL-C level at the start of the study was 2.5 [2.0, 3.0] mmol/L (98 [77, 115] mg/dL), which decreased to 1.3 [0.7, 1.7] mmol/L (49 [29, 67] mg/dL) after 8weeks of evolocumab treatment, resulting in an mean (SD) 50.9 (28.6) % reduction and 1.4 (1.0) mmol/L (55.1 (37.9) mg/dL) absolute reduction. At follow-up, 55.1% and 78.7% of patients achieved LDL-C goals of < 1.4mmol/L (55mg/dL) and < 1.8mmol/L (70mg/dL), respectively. No adverse or serious adverse drug reactions were reported. Evolocumab treatment was associated with significant LDL-C lowering and favorable safety and guideline-recommended LDL-C goal achievement rates among patients with ACS in the real-world clinical practice setting in South Korea.

Long-term effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia: an observational case series

BackgroundWe assessed long-term real-world effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia (HoFH).MethodsRetrospective case series of six patients with HoFH treated with lomitapide in an Italian clinic. Changes in low-density lipoprotein cholesterol (LDL-C) during lomitapide treatment were assessed. The effect on LDL-C of PCSK9 inhibitors, apheresis and lomitapide was evaluated. Additionally, high-density lipoprotein cholesterol (HDL-C), gastrointestinal tolerability, hepatic steatosis/elasticity, transaminases, and cardiovascular events and symptoms were assessed.ResultsMedian age at HoFH clinical and molecular diagnoses was 25 (range 2–49) and 40 (29–71) years, respectively. Five (83.3%) had prior cardiovascular events. One patient received apheresis, which was subsequently discontinued. All patients received PCSK9 inhibitors but discontinued due to minimal effectiveness. Median (range) age at lomitapide initiation was 44 (28–73) years, with a median 47 (18–85) months’ treatment (mean dose 17.5 [5–40] mg/day). Mean (SD) baseline LDL-C was 263.2 (148.1) mg/dL, which decreased by 80% at nadir (52.8 [19.2] mg/dL) and 69% at last follow-up (81.3 [30.5] mg/dL). Four patients (66.7%) achieved LDL-C < 70 mg/dL sometime during follow-up, all of whom also achieved LDL-C < 55 mg/dL. Adverse events (AEs) were generally mild to moderate, hepatic steatosis was either absent or mild/moderate and hepatic elasticity remained normal in all but two patients (> 70 years old). All patients with reported cardiovascular symptoms had improvements in symptoms, and all patients reported stabilization or regression of intima-media thickness and atheromatous plaques.ConclusionsThese long-term, real-world data demonstrate that lomitapide substantially reduced LDL-C for up to seven years. Most patients achieved LDL-C goal at some point, consistent with published Phase III trial and real-world evidence data. No patient discontinued lomitapide treatment. Further long-term follow-up in a larger patient population will be important to determine cardiovascular and other outcomes.

Low-Density Lipoprotein Cholesterol Goal Achievement and Self-Reported Medication Adherence: Insights from the JET-LDL Registry

Low-Density Lipoprotein Cholesterol Goal Achievement and Self-Reported Medication Adherence: Insights from the JET-LDL Registry

LIpid Response to Statins ± Ezetimibe In Mumbai (LIRIM): A Cross-sectional Observational Study.

India has the highest burden of cardiovascular disease (CVD) among developing nations. Data from international studies show significant underimplementation of recommended aggressive lipid-lowering strategies for achieving low-density lipoprotein cholesterol (LDL-C) goals, especially after percutaneous coronary intervention (PCI), a pattern also observed in India. Moreover, ethnic variation in response to statin therapy has prompted clinicians to adopt lower doses of statin therapy in Asians to achieve comparable LDL-C lowering. To document the dose of statin ± ezetimibe required to achieve the European Society of Cardiology (ESC) goals of LDL-C <55 mg/dL in Indian patients with established atherosclerotic cardiovascular disease (ASCVD). This retrospective single-center, cross-sectional, observational, all-comers study in Mumbai evaluated the dose of atorvastatin (A)/rosuvastatin (R) ± ezetimibe (E) treatment at which patients with established ASCVD (n = 542), irrespective of their baseline level, achieved LDL-C goals (<55 mg/dL). Those with LDL-C levels >55 mg/dL on current therapy were switched to R 40 mg ± E 10 mg daily. The final data set (n = 340) included those who achieved LDL-C goals at the initial visit and those at follow-up. The primary and secondary outcomes assessed the impact of R 40 mg ± E 10 mg (R40 ± E10) on LDL-C (<55 mg/dL) and non-high-density lipoprotein cholesterol [non-HDL-C (<85 mg/dL)] goal achievement, respectively. At the end of follow-up, LDL-C <55 mg/dL was observed in 42.16% of patients (n = 113) with R40 and in another 43.28% (n = 116) with R40 + E10. A few patients (n = 39; 14.6%) achieved this goal with other dosages. Similarly, non-HDL-C <85 mg/dL was observed in 39.3% of patients (n = 107) with R40 and in another 47.4% of patients (n = 129) with R40 + E10. Overall, around 20% of patients were unable to achieve their LDL-C and non-HDL-C goals despite being on high-intensity statin ± E therapy. In the first report of its kind in India, this study showed that suboptimal LDL-C goal achievement occurred in around 20% of high-risk ASCVD patients on dual therapy. This indicates that clinicians should consider the addition of other therapies [e.g., bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and inclisiran] to mitigate the residual risk. Several more trials are needed to determine the most suitable treatment regimen for this population.

LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

An “Inclisiran First” Strategy vs Usual Care in Patients With Atherosclerotic Cardiovascular Disease

BackgroundMost patients with atherosclerotic cardiovascular disease fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals. Twice-yearly inclisiran lowers LDL-C by ∼50% when added to statins. ObjectivesThis study evaluated the effectiveness of an “inclisiran first” implementation strategy (adding inclisiran immediately upon failure to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) vs representative usual care in U.S. patients with atherosclerotic cardiovascular disease. MethodsVICTORION-INITIATE, a prospective, pragmatically designed trial, randomized patients 1:1 to inclisiran (284 mg at days 0, 90, and 270) plus usual care (lipid management at treating physician’s discretion) vs usual care alone. Primary endpoints were percentage change in LDL-C from baseline and statin discontinuation rates. ResultsWe randomized 450 patients (30.9% women, 12.4% Black, 15.3% Hispanic); mean baseline LDL-C was 97.4 mg/dL. The “inclisiran first” strategy led to significantly greater reductions in LDL-C from baseline to day 330 vs usual care (60.0% vs 7.0%; P < 0.001). Statin discontinuation rates with “inclisiran first” (6.0%) were noninferior vs usual care (16.7%). More “inclisiran first” patients achieved LDL-C goals vs usual care (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; P < 0.001). Treatment-emergent adverse event (TEAE) and serious TEAE rates compared similarly between treatment strategies (62.8% vs 53.7% and 11.5% vs 13.4%, respectively). Injection-site TEAEs and TEAEs causing treatment withdrawal occurred more commonly with “inclisiran first” than usual care (10.3% vs 0.0% and 2.6% vs 0.0%, respectively). ConclusionsAn “inclisiran first” implementation strategy led to greater LDL-C lowering compared with usual care without discouraging statin use or raising new safety concerns. (A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an “Inclisiran First” Implementation Strategy to Usual Care on LDL Cholesterol [LDL-C] in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C [≥70 mg/dL] Despite Receiving Maximally Tolerated Statin Therapy [VICTORION-INITIATE]; NCT04929249)

Novel and Emerging LDL-C Lowering Strategies: A New Era of Dyslipidemia Management.

Atherosclerotic cardiovascular disease (ASCVD) represents a major global health challenge, significantly contributing to mortality rates. This chronic inflammatory condition affecting blood vessels is intricately linked to hypercholesterolemia, with elevated levels of low-density lipoprotein cholesterol (LDL-C) recognized as a central and modifiable risk factor. The effectiveness of lipid-lowering therapy (LLT) in mitigating ASCVD risk is well established, with studies revealing a substantial reduction in major ischemic events correlating with LDL-C reduction. While statins, often combined with ezetimibe, remain fundamental in dyslipidemia management, a significant proportion of patients on statin therapy continue to experience cardiovascular events. Recent pharmacological advancements, driven by a deeper understanding of atherogenesis, have unveiled novel therapeutic targets and potent drugs. Notably, agents like bempedoic acid and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab, inclisiran) have emerged as effective options to intensify LLT and achieve LDL-C goals, addressing limitations associated with statins, such as myopathy. Molecular insights into alternative pathways have spurred the investigation of emerging agents, offering promising perspectives for novel medications with efficacy comparable to established treatments, associated with advantages in cost and administration. This review provides a comprehensive overview of the evolving landscape of lipid-lowering strategies, highlighting the progress made in addressing ASCVD risk and the potential of upcoming therapies to further optimize cardiovascular prevention.

Is there a role for earlier use of combination therapy?

As the global population ages and cardiovascular risk factors rise, we can expect a continued increase in atherosclerotic disease. Low-density lipoprotein cholesterol (LDL-C) reduction is a cornerstone of cardiovascular risk reduction with strong, causal evidence indicating that the greatest benefit is derived from early and large decreases in LDL-C. Despite the adoption of statins as the backbone of lipid-therapy regimens, numerous studies and registry analyses reveal our collective inability to achieve LDL-C goals in high-risk patients. Combination therapy with ezetimibe has been shown to result in statistically significant decreases in LDL-C level, atheroma volume, and cardiovascular adverse event rates. A major barrier to implementing an upfront combination therapy approach is the perceived side effects from therapeutic agents although multiple studies show that a therapeutic patient-physician relationship could overcome this issue. Novel agents such as PCSK-9 inhibitors, bempedoic acid, and inclisiran have the potential to achieve similar outcomes although additional research is needed regarding the cost effectiveness of these approaches. Despite these hurdles, there is a role for the newer agents early in the disease course of high-risk patients such as those with markedly elevated LDL-C >190 mg/dL and FH.The implementation of upfront combination therapy, especially in high-risk patients, will decrease clinical inertia while allowing for earlier consideration of newer, effective agents to decrease cardiovascular burden.

A retrospective nationwide analysis of evolocumab use in Sweden and its effect on low-density lipoprotein cholesterol levels.

Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment. Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively. Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (n = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (n = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively. The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.

Low-Density lipoprotein cholesterol goal achievement and associated factors among type 2 diabetes mellitus patients at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia: Cross-sectional Study, 2023

BackgroundAchieving the recommended low-density lipoprotein cholesterol goal is vital for managing cardiovascular risk. However, research on low-density lipoprotein cholesterol goal achievement and associated factors in Sub-Saharan Africa, particularly in Ethiopia, is limited. While global rates vary from 18% to 73%, there is a need for further investigation in this region to better understand and address the factors influencing low-density lipoprotein cholesterol goal attainment.The objective was to assess low-density lipoprotein cholesterol goal achievement and associated factors among type 2 diabetes patients. MethodsInstitution based quantitative cross-sectional study design was conducted among type II diabetes patients at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia.Systematic random sampling technique was used to select patient records. Data was collected by using a structured and pretested checklist and some variables were also collected from the chart review, structured questionnaire and analyzed using Epi info version 7.2 and SPSS version 25. Bivariate and multivariable logistic regressions were performed to examine the association between variables. Adjusted odds ratios (AOR) with 95 % confidence intervals were calculated, and a p-value of ≤ 0.05 was considered statistically significant for associations between independent and outcome variables. ResultThe LDL goal achievement among type II diabetes patients is 58.9 %.Total triglyceride level (AOR = 0.19, 95 %CI, 0.12, 0.54, P= <0.0001), history of smoking (AOR = 0.198, 95 %CI, 1.06, 1.10, P < 0.0001), 40–65 years of age (AOR = 0.21, 95 %CI, 0.05, 0.87, P = 0.03), BMI (AOR = 0.19, 95 %CI, 0.12, 0.54, P= <0.0001)., were found to be statistically significant independent predictors for LDL Goal Achievement in type II Diabetes patients. ConclusionIn the current study, significant proportions of type II DM patients fail to attain acceptable levels of LDL cholesterol. Factors like total triglyceride levels, smoking history, older age, and increased BMI influenced low-density lipoprotein cholesterol goal achievement. Advanced in age, increase in BMI, smoking, and higher levels of triglyceride were determinants of LDL cholesterol goal achievement. Patient education on life style modification mainly cessation of smoking diet and exercise may be recommended to achieve the LDL cholesterol goal.

Clinical characteristics and treatment patterns in patients with atherosclerotic cardiovascular disease with hypercholesterolemia: a retrospective analysis of a large US real-world database cohort

Objective Guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) recommend lipid-lowering therapies (LLTs) to reduce low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. This study described LLT utilization patterns and LDL-C goal achievement (to <70 mg/dL) among patients with ASCVD in the United States. Methods This retrospective study was conducted using Optum’s de-identified Clinformatics Data Mart Database (CDM). Patients with their first ASCVD diagnosis (index date) in the CDM database between July 1, 2015, and December 31, 2018, were followed for ≥12 months to assess LLT utilization patterns and change in LDL-C. LLTs included were statins and non-statin LLTs (ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 inhibitors). Adherence was measured as the proportion of days covered (PDC), defined as the number of days with drug on-hand (or number of days exposed to drug) divided by the 12-month follow-up period. Patients with PDC ≥0.8 were considered adherent. Results Among the patients with ASCVD (N = 1,424,893) included in this study, only 621,978 (43.7%) had at least one LDL-C measurement at baseline (6 months prior to and 3 months after the index date). The mean age was 71.5 years, and almost half of the patients were female. Patients were followed for a mean (standard deviation [SD]) duration of 30.6 (11.4) months (median of 29.9 months). During the follow-up, about one-quarter of the patients did not receive any LLT. Among treated patients, 89.5% received statins and 10.5% received non-statin LLT. Less than half (47.6%) of the patients were adherent to the index treatment during the 12-month follow-up. Even in patients receiving combination therapy (statin + non-statin LLT), a sizable proportion (35.8%) showed an increase in LDL-C over the follow-up period. Conclusions This retrospective study highlighted limited LDL-C monitoring in patients with ASCVD, and unmet need in terms of suboptimal utilization of non-stain LLTs, limited adherence to LLTs, and inadequate lipid control after treatment (among those with LDL-C measurements during the follow-up period) need to be addressed to improve outcomes in this patient cohort.

Real vs perceived LDL cholesterol control in clinical practice in Spain: Which factors are related to real control?

Abstract Background/Introduction According to ESC Guidelines, low-density lipoprotein cholesterol (LDLc) reduction is essential for the control of dyslipidaemia. Frequently, the physicians’ perception of LDLc control in patients (pts) is higher than the actual control, potentially leading to a suboptimal management of these pts. Purpose To understand the impact of physicians’ perception on LDLc control using a multivariate analysis and identify other potential predictive factors in the management of pts with dyslipidaemia in Spain. Methods Cross-sectional and multicentre study that included 435 healthcare professionals (34% cardiologists, 28% General Practitioners [GPs], 24% internists, and 14% endocrinologists) from 145 healthcare areas in Spain. Qualitative and quantitative information related to the management of pts with dyslipidaemia in clinical practice was collected. Additionally, aggregated anonymized data of the last 10 pts with dyslipidaemia attended by each physician were collected. With these data, a multivariate analysis was performed to estimate the impact of different variables on real LDLc control, including: age, gender and speciality of the physician, category of prevention, presence of comorbidities, lipid-lowing therapy (LLT) used, and whether the physician accurately perceived the real LDLc control. Results 4,010 pts (8%, 13%, 16% and 61% with low, moderate, high, and very high CV risk) were included. Physicians’ perception was that 62% of the pts achieved LDLc goals, but in actual clinical practice only 31% of pts did (p&amp;lt;0.01) (Figure 1). In the multivariate analysis it was found that physicians’ age and gender had little to no effect on LDLc control of pts, while their speciality did: cardiologists were twice as likely to control patients with dyslipidaemia than GPs. Likewise, pts with comorbidities or on secondary prevention were statistically associated with lower chance of appropriate LDLc control. Regarding the treatment used, data showed that the proportion of pts achieving LDLc goals increased as higher potency LLT was used. Precisely, LLT was found to have an significant impact on LDLc control: when compared to low intensity statins, pts treated with the combination of statin + ezetimibe had twice as many chances of achieving LDLc goals, reaching up to almost 15 times more possibilities for pts using PCSK9i. Lastly, control perception also mattered, with physicians who accurately perceived the real control having a probability two times higher to control their pts than physicians with poor LDLc control perception. Conclusions In Spain, most pts with dyslipidemia do not achieve the recommended LDLc goals mainly because of an insufficient intensification of LLT. The multivariate analysis showed that both LLT intensity and physicians’ perception had a major effect on LDLc control. These data highlight the need to further intensify LLT and raise awareness among physicians of the importance of achieving LDLc targets.Perceived vs real LDLc control by riskMultivariate analysis results

Low-density-lipoprotein cholesterol target attainment in high-risk patients with history of diabetes or major adverse cardiac and cerebrovascular event: an (un)expected gender bias

Abstract Background Lowering low-density lipoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular disease prevention, especially after the occurrence of a major adverse cardiac and cerebrovascular event (MACCE). Collection of epidemiological data is crucial for monitoring healthcare appropriateness and the fulfillment of guidelines recommendations. Purpose This analysis aimed to evaluate the proportion of high-risk patients who achieved LDL-C goal as suggested by the international guidelines by analyzing regional administrative data and to explore the predictors of therapeutic failure, with a focus on the role of gender. Methods By linking health administrative and laboratory data, we collected data from seven Local Health Districts on residents aged ≥45 years. Inclusion criteria were: 1) at least one LDL-C measurement in the year; 2) a history of MACCE (defined as myocardial infarction and/or stroke and/or revascularization of the coronary, carotid, or peripheral arteries) and/or type 2 diabetes mellitus (T2DM). Cohorts were defined at 1st January 2019 and 1st January 2020. Lipid lowering therapy use (defined as ≥2 prescription fillings or ≥75% coverage of treatment days) over the past 6 months if LDL-C data were available or over the past year if no LDL-C data were available was monitored. The outcome was the number of patients with on-treatment LDL-C optimal levels, as defined by levels &amp;lt;55 mg/dl for patients with MACCE and &amp;lt;70 mg/dl for patients with T2DM without MACCE. Results A cohort of 174,200 individuals was analyzed (55% males). As regards subjects on lipid-lowering therapies, we found that female gender was associated with a significantly lower probability to have LDL-C levels at target (OR: 0.58±0.01; p&amp;lt;0.0001) in patients with MACCE with or without T2DM, in a model adjusted for age, district area, and the presence of cardiovascular risk factors and comorbidities (renal failure, heart failure, atrial fibrillation). This result was confirmed also in the analysis conducted in subjects without lipid-lowering therapies (OR: 0.56±0.01; p&amp;lt;0.0001). No significant differences were documented by stratifying for the presence of clinical pathways aimed to the active call of the patients by clinicians ("Initiative Health"). Conclusions These results demonstrated that females have a significantly lower probability to reach LDL-C levels recommended targets. This datum is confirmed even in the absence of lipid-lowering therapies. These results call for action aimed to: 1) education for general population and for patients with MACCE with a specific target on females; 2) information for clinicians for the need of assessing adequate lipid-lowering therapy prescription and adherence irrespectively of gender; 3) organization of clinical pathways - from admission to recovery and follow-up - with a specific focus on secondary prevention target attainment.

Abstract 11893: Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia

Background: Ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in the phase 2 trial. A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on background lipid-lowering therapy (LLT). Methods: This was a randomized, double-blind, placebo-controlled, 52-week trial conducted in China (NCT02662569). Eligible patients receiving stable statin (±ezetimibe) therapy but not achieving LDL-C goals were enrolled. Patients were randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or placebo subcutaneously every 2 weeks (Q2W), or ongericimab 300 mg or placebo subcutaneously every 4 weeks (Q4W) for 52 weeks. The primary endpoint was percent change in LDL-C from baseline to week 24. Results: A total of 806 patients were randomized, 802 patients received at least one dose of ongericimab or placebo. The least-squares (LS) mean difference between ongericimab and placebo in LDL-C from baseline to week 24 was -67.7% (95% CI: -72.49%, -62.99%; p &lt; 0.0001) in Q2W group and -61.2% (95% CI: -67.09%, -55.21%; p &lt; 0.0001) in Q4W group. LDL-C reductions were maintained to Week 52. Ongericimab also favorably altered other lipid parameters (Table 1). The overall incidence of adverse events was similar between ongericimab and placebo. Conclusion: Ongericimab on stable background LLT significantly reduced LDL-C and was well tolerated in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia.