Low-density Lipoprotein Cholesterol Goal Research Articles

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.

12369 Clinical Experience With Inclisiran At An Academic Center

Abstract Disclosure: L. Chavez Marin: None. M. Gonzalez: None. M.F. Linton: None. B.G. Carranza Leon: None. Background: Inclisiran, a small interfering RNA (siRNA) molecule designed to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), is the only siRNA approved for management of elevated low-density lipoprotein cholesterol (LDL-C) in both primary (for patients with familial hypercholesterolemia) and secondary prevention of cardiovascular disease. In clinical trials, Inclisiran has been shown to reduce LDL-C by more than 50% in populations at high cardiovascular risk. However, real world data about its tolerability and efficacy is still limited. Methods: We conducted an electronic medical record search to identify subjects who were prescribed Inclisiran at a lipid clinic within Vanderbilt University Medical Center (Nashville, USA). Subjects were included if they received at least one dose of Inclisiran and had pre- and post- LDL-C levels. Subjects taking other LDL-C lowering medications like statins, ezetimibe, bempedoic acid, and PCSK-9 inhibitors were included. Pre- and post- LDL-C averages were calculated and analyzed with 95% confidence intervals. The reasons for medication discontinuation were also examined. Results: Out of 69 subjects identified, only 19 met criteria for inclusion, while 32 never received a dose due to cost burden and insurance denial. The other 18 subjects were not included due to inadequate lab results at the time of data collection. In subjects who received at least one dose of Inclisiran, average pre-LDL-C was 142 mg/dL [CI: 34.7] while post-LDL-C was 77 mg/dL [CI: 24.0], notable for a 46% decrease in LDL-C levels. These subjects were also receiving another lipid lowering agent, like a statin, or had previously used a monoclonal antibody-PCSK-9 inhibitor. Those without prior use of PCSK-9 inhibitors were also analyzed. Average pre-LDL-C was 109.5 mg/dL [CI: 15.8] while post-LDL-C was 39.8 mg/dL [CI: 17.2], which revealed a 64% decrease in LDL-C levels. The main reason for discontinuation of Inclisiran was insurance denial followed by individual preference. Only one subject discontinued Inclisiran due to experiencing a generalized rash. Conclusions: Inclisiran is an effective and overall well-tolerated medication indicated for the management of elevated LDL cholesterol. Our study revealed that for individuals with above goal LDL-C, despite maximum tolerated therapy with a statin, additional LDL-C lowering benefits can be seen with Inclisiran use. However, insurance approval and cost burden seem to be the main barriers for access. Presentation: 6/3/2024

Optimization of Hypercholesterolemia Treatment after Heart Transplant: The Role of PCSK9 Inhibitors.

Previous studies have reported the benefit of statins after heart transplant (HT). However, the use of high-dose statins might be limited in some HT patients due to intolerance and interactions with immunosuppression or might not be enough to achieve low-density lipoprotein (LDL) cholesterol goals. Hyperlipidemia has been associated with coronary allograft vasculopathy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors might be a safe and effective option in HT patients with suboptimal lipid control. In a retrospective study, we identified HT patients in our center with LDL cholesterol >100 mg/dL, after diet modifications and up-titration of statins to maximum tolerated dose, treated with PCSK9i. The primary endpoint was LDL reduction one month after, and secondary endpoints were the development of donorspecific HLA antibodies (DSA) and the presence of coronary allograft vasculopathy or rejection. From January, 2018, to January, 2024, we identified five HT patients treated with PCSK9 inhibitors. In all cases, evolocumab was used. A significant reduction in LDL cholesterol was observed (151.6 ± 13.5 mg/dl to 72.4 ± 14.6 mg/dl; p = 0.04, mean reduction 75.7 ± 14.1 mg/dl), as well as in total cholesterol (231 ± 34.6 mg/dl to 152.2 ± 38.9 mg/dl; p < 0.01, mean reduction 78.8 ± 22.2 mg/dl). A significant increase in HDL cholesterol was not observed (45.4 ± 10.9 mg/dl to 46.2 ± 11.1 mg/dl; p = 0.60). One patient developed DSA five years after treatment onset. Rejection and coronary allograft vasculopathy were not observed. PCSK9 inhibitors are safe and effective in reducing LDL in HT patients. However, larger studies are needed to clarify if they can reduce the development of coronary allograft vasculopathy.

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

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

Addition of Bempedoic Acid to Statin-Ezetimibe versus Statin Titration in Patients with High Cardiovascular Risk: A Single-Centre Prospective Study.

Reducing levels of low-density lipoprotein cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk and with LDL-C above 70 mg/dL. They were randomly divided into two groups: the bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group, including patients who doubled the dose of statin. At 12 weeks, the BA group presented a more significant decrease in LDL-C compared to the ST group (-22.9% vs. 7.5% p 0.002). The total cholesterol decreased significantly in the BA group compared to ST (-14.8% vs.-4.7%; p 0.013) No significant between-group changes in HDL and triglycerides occurred. At 12 weeks, the number of patients who reached LDL-C lower than 70 mg/dL was 38 (63%) in the BA group versus 22 (37%) in the ST group (between groups, p 0.034). In the BA group, the LDL-lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of bempedoic acid to statin-ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C levels and increased the number of patients reaching the LDL-C goal.

Lipid-lowering therapy in patients with coronary heart disease: an Italian real-life survey. Results from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES) in Italy.

In patients at high cardiovascular risk, a low-density lipoprotein cholesterol (LDL-C) reduction of ≥50% from baseline and an LDL-C goal of <70 mg/dL (or <55 mg/dL in very high-risk patients) are recommended. Multiple registry and retrospective studies have shown that patients with high atherosclerotic cardiovascular risk often do not reach the targets defined by the European Society of Cardiology guidelines as a result of suboptimal management of LDL-C. Here, we report the data on lipid-lowering therapy and lipid targets from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES), an observational, prospective study designed to collect data on patients with ischemic heart disease treated at cardiac outpatient clinics across the Italian national territory. We included patients with known coronary heart disease (CHD) who underwent follow-up visits at various outpatient cardiology clinics. A total of 2532 patients were included (mean age: 67±17 years, 80% male). Among patients with available laboratory data (n=1712), 995 (58%) had LDL-C<70 mg/dL, 717 (42%) had LDL-C≥70 mg/dL, and 470 (27%) had LDL-C<55 mg/dL. Patients who more frequently achieved the recommended LDL-C levels were male, had diabetes, had a higher educational level, and performed intense physical activity. Statins were used in 2339 (92%) patients, high-intensity statins (e.g., rosuvastatin 20/40 mg or atorvastatin 40/80 mg) in 1547 patients (61% of the whole population and 66% of patients on statins), and ezetimibe in 891 patients (35%). Patients receiving high-intensity statins tended to be younger, not to have diabetes, and to have been included in a cardiac rehabilitation program. In a real-world sample of Italian patients with CHD, adherence to lipid-lowering therapy fell markedly short of optimal levels. Many patients did not achieve the LDL-C target of 70 mg/dL, and even fewer reached the LDL-C target of 55 mg/dL. Notably, patients with a lower educational level had a greater likelihood of being undertreated. Strategies aimed at improving preventive interventions for CHD and overcoming social disparities should be evaluated and optimized.

Low LDL-C: Is It all Good News?

This review presents the risks and benefits of very low LDL cholesterol and the safety of using lipid-lowering therapy to achieve these levels. A growing body of literature suggests that lower LDL cholesterol levels are associated with a reduced risk of cardiovascular disease. Further, achieving these levels with pharmaceuticals is remarkably safe. Although statins may slightly increase the risk of diabetes mellitus and hemorrhagic stroke, the benefits outweigh the risks. While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals.

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.

Characteristics of Patients With Atherosclerotic Cardiovascular Disease in Belgium and Current Treatment Patterns for the Management of Elevated LDL-C Levels.

Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level. We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons. Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined. Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal. Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice.

Lipoprotein (a) is a predictor of non-achievement of LDL-C goals in patients with chronic heart disease

Introduction and objectivesLipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease (CAD), and to assess its influence on the achievement of LDL-C targets. MethodWe conducted a cross-sectional study in a Cardiology department in Spain. A total of 870 patients with stable CAD had their lipid profile determined, including Lp(a). Patients were stratified into two groups according to Lp(a) >50 mg/dL and Lp(a) ≤50 mg/dL. The association of Lp(a) >50 mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis. ResultsThe prevalence of Lp(a) >50 mg/dL was 30.8%. Patients with Lp(a) >50 mg/dL had higher baseline (142.30 ± 47.54 mg/dL vs 130.47 ± 40.75 mg/dL; p = 0.0001) and current (72.91 ± 26.44 mg/dL vs 64.72 ± 25.30 mg/dL; p = 0.0001), despite the fact that they were treated with more high-potency statins (77.2% vs 70.9%; p = 0.058) and more combination lipid-lowering therapy (LLT) (37.7% vs 25.7%; p = 0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a) >50 mg/dL. Independent predictors of having elevated Lp(a) levels >50 mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08−2.14), combination LLT with ezetimibe (OR 2.0; 95% CI 1.45−2.73) and failure to achieve a LDL-C ≤55 mg/dL (OR 2.3; 95% CI 1.63−3.23). ConclusionsElevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.

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.

Comparison of Various Low Density Lipoprotein Cholesterol Calculators: Is It Time for the Friedewald Equation to Go in India?

Low-density lipoprotein cholesterol (LDL-c) is the main target in the management of dyslipidemia in primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Our study aims to compare the conventional and most popular Friedewald equation, and the more recent Sampson equation (literally unknown in India but more accurate), to the directly estimated LDL-c by the homogenous method. No such comparative study has been done in India. A multicenter retrospective analysis of the lipid profiles of patients whose LDL-c was derived directly by the homogenous method was included. Indirect LDL-c was estimated using the Friedewald and Sampson equations. The accuracy, error, and level of correlation between direct LDL-c and the two equations were assessed for concordance and discordance based on LDL-c categories (≤50, 51-70, 71-100, 101-130, ≥131 mg/dL). Upward discordance is when the calculated LDL-c was at least one category higher and downward discordance is when the calculated LDL-c was at least one category lower than the corresponding direct LDL-c (DLDL-c). Subgroup analyses were also done for triglycerides (TGLs) <150, 151-199, ≥200 mg/dL. TGL >400 were assessed separately. A total of 30,810 samples from four centers were studied. The overall mean DLDL-c was 107.86 mg/dL. The mean estimated LDL-c by Friedewald's equation (FLDL-c) and Sampson's equation (SLDL-c) were 101.37 and 104.37 mg/dL, respectively. There was statistical significance (p-value < 0.0005) in the mean difference when DLDL-c was compared with combined SLDL-c and FLDL-c as per the Games-Howell multiple comparison study, in which the mean difference was greater with the Friedewald equation (6.495) than with the Sampson equation (3.491). The overall concordance between FLDL-c vs DLDL-c and SLDL-c vs DLDL-c was nearly similar (74 vs 77%, respectively). The overall discordance upward was 5% with FLDL-c and 7% with SLDL-c (p-value < 0.0005). The overall discordance downward for FLDL-c and SLDL-c was 22 and 15% (p-value < 0.0005). When subgroup analysis was done for LDL-c ≤ 70, the downward discordance was 41% (FLDL-c) and 32% (SLDL-c), giving a false sense of goal LDL-c being achieved more often with FLDL-c. For LDL-c > 70, the corresponding downward discordance was 16 and 11%, respectively. Starting from TGL ≥ 200 mg/dL, there was consistent underestimation of LDL-c by the Friedewald equation. When TGL was > 400, the mean DLDL-c was 109 mg/dL, while for FLDL-c, it was 82 mg/dL and for SLDL-c, it was 98 mg/dL. Sampson's equation improves the accuracy of the indirectly calculated LDL-c compared to Friedewald's equation. The FLDL-c is estimated falsely low at LDL-c ≤ 70 mg/dL, giving a lower sense of LDL-c goal being achieved, and these patients will be undertreated. By switching to Sampson's equation, 9% in the LDL-c ≤ 70 mg/dL and 5% in the LDL-c > 70 mg/dL can be correctly classified. The shift to Sampson's equation requires a simple formula change and can be easily embraced in India-a small change but in the right direction.

Management of dyslipidaemia in patients with comorbidities: facing the challenge.

Dyslipidaemia is a common chronic kidney disease (CKD) and contributes to excessively elevated cardiovascular mortality. The pathophysiology is complex and modified by comorbidities like the presence/absence of proteinuria, diabetes mellitus or drug treatment. This paper provides an overview of currently available treatment options. We focused on individuals with CKD and excluded those on renal replacement therapy (haemodialysis, peritoneal dialysis, or kidney transplantation). The use of statins is safe and recommended in most patients, but guidelines vary with respect to low-density lipoprotein (LDL) cholesterol goals. While no dedicated primary or secondary prevention studies are available for pro-protein convertase subtilisin/kexin type 9 inhibitors, secondary analyses of large outcome trials reveal no effect modification on endpoints by the presence of CKD. Similar data have been shown for bempedoic acid, but no definite conclusion can be drawn with respect to efficacy and safety. No outcome trials are available for inclisiran while the cholesterol lowering effects seem to be unaffected by CKD. Finally, the value of fibrates and icosapent ethyl in CKD is unclear. Lipid abnormalities contribute to the massive cardiovascular disease burden in CKD. Lowering of LDL cholesterol with statins (and most likely PCSK9 inhibitors) reduces the event rate and thus statin therapy should be initiated in almost all individuals. Other interventions (bempedoic acid, inclisiran, fibrates, or icosapent ethyl) currently need a case-by-case decision before prescription.

LDL-cholesterol goal achievement in familial hypercholesterolemia patients followed at a secondary hospital

LDL-cholesterol goal achievement in familial hypercholesterolemia patients followed at a secondary hospital

Clinical Considerations for HealthcareProvider-Administered Lipid-Lowering Medications.

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack oftimely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the "buy-and-bill" process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.

Navigating Cardiovascular Risk and Lipid Management in Indian Patients: Key Messages from the Lipid Association of India 2024 Consensus Statement IV.

Effective lipid management is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). The Western lipid guidelines may not apply to Indian subjects because of the vast differences in cardiovascular (CV) disease epidemiology. To overcome this challenge, the Lipid Association of India (LAI) in 2016 proposed an ASCVD risk stratification algorithm. The appropriate low-density lipoprotein cholesterol (LDL-C) goals for various risk groups were proposed, with an LDL-C target of <50 mg/dL recommended for the first time globally for patients in the very high-risk group. Subsequently, in 2020, an extreme risk group was added because of observations that patients with more severe or extensive ASCVD, along with multiple risk factors and comorbidities, had increased rates of adverse CV events and could benefit from more intensive LDL-C lowering. The extreme risk group was subdivided into categories A and B, with LDL-C targets as low as 30 mg/dL or lower. The availability of further evidence regarding the significance of novel risk factors and the availability of new LDL-C lowering therapies necessitated refining the ASCVD risk assessment algorithm, defining LDL-C targets for subjects with these risk factors, and incorporating recommendations for attaining very low LDL-C levels in a defined, select group of patients. Accordingly, the LAI expert group recently published the Consensus Statement IV, which is a comprehensive document addressing several key issues about risk stratification and dyslipidemia management in Indian subjects. LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) are not only primary and co-primary targets for lipid-lowering therapy but also risk factors for ASCVD risk stratification. Apolipoprotein B is a secondary target. The risk assessment algorithm has been updated to incorporate several nonconventional yet relevant CV risk factors. Additionally, the role of subclinical atherosclerosis has been highlighted. The CV risk due to subclinical atherosclerosis has been considered equivalent to that of established ASCVD, and hence, similar LDL-C targets have been recommended. Furthermore, a new risk category-extreme risk group category C has been added for the small subgroup of patients who continue to experience ASCVD sequelae despite achieving LDL-C levels of 30 mg/dL or lower. An ultralow LDL-C target (10-15 mg/dL) has been recommended along with optimal control of risk factors and guideline-directed management of comorbidities. Dyslipidemia management should be effective with sustained LDL-C lowering. In high-risk situations (e.g., acute coronary syndrome), the LDL-C target should be achieved as early as possible, preferably within the first 2 weeks. The present document summarizes the key messages from the LAI Consensus Statement IV.

Treat-to-target or high-intensity statin treatment in older adults with coronary artery disease: a post hoc analysis of the LODESTAR trial.

The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16mg/dl in the treat-to-target strategy group and 64 ± 18mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. ClinicalTrials.gov, NCT02579499.

Uso de nuevas terapias hipolipemiantes en la práctica clínica. Consenso SEC/SEA/SEEN/SEMFYC/SEMERGEN/SEMG/SEN/SEACV/S.E.N.

Although in the last years a better control of vascular risk factors has been achieved, «real-world» data showed that only a few percentage of patients reach low-density lipoprotein-cholesterol goal levels. Recently, new therapies for the management of dyslipidaemias have emerged, and they could help to achieve the goal targets recommended by currents practical clinical guidelines so as to reduce vascular outcomes. Nevertheless, it is still uncertain in daily clinical practice the ideal timing of prescribing these new drugs, and what are the patients more benefited, compared to «classical» therapies such as statins and/or ezetimibe. In this complex scenario, this consensus document is proposed. It is certified by most of the scientific societies of clinical specialties that may play a role in the patient-healthcare process of atherosclerotic disease (SEC/SEA/SEEN/SEMFYC/SEMERGEN/SEMG/SEN/SEACV/S.E.N.), and its aim is to recommend some practical and simple guidelines, based on current scientific evidence, for the management of new therapies for dyslipidaemias in different scenarios of daily clinical practice.

Use of combination therapy is associated with improved LDL cholesterol management: 1-year follow-up results from the European observational SANTORINI study.

To assess whether implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines observed between 2020 and 2021 improved between 2021 and 2022 in the SANTORINI study. Patients with high or very high cardiovascular (CV) risk were recruited across 14 European countries from March 2020 to February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein (LDL) cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. Of 9559 patients enrolled, 9136 (2626 high risk and 6504 very high risk) had any available follow-up data, and 7210 (2033 high risk and 5173 very high risk) had baseline and follow-up LDL-C data. Lipid-lowering therapy was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6 and 25.6% to 57.1 and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 to 2.0 mmol/L. Goal attainment improved from 21.2 to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs. 25.5%). Lipid-lowering therapy use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal; hence, strategies are needed to improve the implementation of combination LLT.