Search

• PCSK9 inhibitors reduce LDL-C by 58% in heterozygous familial hypercholesterolemia. • Response was significantly higher when maximally tolerated statin therapy is used. • Most patients reach an LDL cholesterol goal according guidelines. • PCSK9 inhibitors are highly effective in FH patients in clinical practice setting. [Display omitted] PCSK9 inhibitors are a treatment option for patients with familial hypercholesterolemia not on low-density lipoprotein cholesterol goals despite the use of maximally tolerated high intensity-statins dose. To evaluate the efficacy of alirocumab and evolocumab in LDL-C reduction and targets attainment in patients with heterozygous familial hypercholesterolemia in clinical practice setting. SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of familial hypercholesterolemia. This study analyze subjects ≥ 20 years of age on stable lipid-lowering therapy, who received PCSK9 inhibitors during the period 2016 to January 2020. 433 patients (mean age 55 years, 53% male, 39% with cardiovascular disease) were included and followed-up for a median of 2.5 years (IQR 1.6–3.0). Median LDL-C level prior to PCSK9 inhibitors was 145 mg/dL (IQR 125–173). The addition of PCSK9 inhibitors (211 alirocumab, 222 evolocumab) reduced LDL-C by 58% (IQR 41–70) p <0.001, in men and women, achieving a median LDL-C level of 62 mg/dL (IQR 44–87) without differences between both PCSK9 inhibitors. Out of them 67% with and 80% without cardiovascular disease reached 2016 ESC/EAS LDL-C targets, and 46% very high risk and 50% high risk patients achieved 2019 ESC/EAS LDL-C goals. Independent predictor factors for attainment of 2019 ESC/EAS LDL-C goals were to be male, smoking and the use of statins with ezetimibe. Both inhibitors were well tolerated. PCSK9 inhibitors on top of maximum lipid-lowering treatment significantly reduced LDL-C levels in patients with familial hypercholesterolemia and improved the achievement of LDL-C targets. [ABSTRACT FROM AUTHOR]

Objective: Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines.Design: Systematic literature review.Data Sources: Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature.Eligibility Criteria: Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]).Data Extraction and Synthesis: Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies-Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test.Results: Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9-56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14-25%]). In individuals with FH, SCORE 5-10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9-22%), 46% (21-55%) and 13% (6-34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only).Conclusions: These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase.Protocol Registration: PROSPERO registration number; CRD77844. [ABSTRACT FROM AUTHOR]

Purpose of Review: The 2013 ACC/AHA Cholesterol guidelines was a major paradigm shift in the management and treatment of dyslipidemia. The new guidelines outlined 'statin benefit groups,' highlighted weighing the benefit versus risks of statin therapy ('net benefit'), and discussed the importance of shared decision making between patients and providers in primary prevention. While there was widespread agreement on the main groups benefiting from statin therapy, there was significant controversy regarding LDL-C goals and thresholds, the role of non-statin therapy, and the use of statins in specific populations. The goal of this review is to understand the rationale for the updated 2016 ACC Expert Consensus on Non-Statins and to contrast it with the 2015 NLA Recommendations on the Management of Dyslipidemia. Recent Findings: The findings of the ACC Expert Consensus Panel were largely influenced by the results of several new clinical trials using non-statin therapy in combination with moderate to high intensity statin therapy. The IMPROVE-IT trial demonstrated that ezetimibe on top of statin therapy lowered ASCVD risk in patients with acute coronary syndromes whose LDL was driven below the previous LDL-C target of <70 mg/dL. In addition, preliminary data assessing the safety of evolocumab and alirocumab on top of statin therapy suggested possible large reductions in ASCVD risk in post hoc analysis. Summary: Both the 2016 ACC Consensus Recommendations and the 2015 NLA Recommendations emphasize the importance of maximally tolerated statin therapy, the use of adjunctive non-statin LDL lowering therapy, and the use of LDL-C goals and thresholds to guide intensification of LDL lowering therapy. Although there are some important differences between the ACC Consensus and NLA recommendations in terms of treatment of special populations (i.e., CHF) and on the use of non-HDL-C goals and thresholds, both guidelines support a role for ezetimibe, bile acid sequestrants, and PCSK-9 inhibitors in patients on maximum tolerated statin therapy. The recent positive results of the FOURIER trial gives additional support to the non-statin recommendations of both the ACC and NLA. [ABSTRACT FROM AUTHOR]

Aims: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting., Methods and Results: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable., Conclusion: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting., Trial Registration: ClinicalTrials.gov number NCT02693548., Competing Interests: Conflict of interest: R.A. received honorary fees for talks and advisory boards from Amgen, Sanofi, MSD, Tecnofarma, Abbott, Saval. O.M.G. received honoraria for speaker or researcher activities from Merck Sharp and Dohme, Amgen, and Sanofi. J.L.D.D. received honoraria for speaker or researcher activities from Merck Sharp and Dohme, Amgen, and Sanofi. L.P.I. received honoraria for speaker or researcher activities from Merck Sharp and Dohme, Astra Zeneca, Esteve, Amgen, and Sanofi. P.M. received honoraria for advisory boards and received research grants from Amgen and Sanofi., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether percent low-density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known.Methods: Patients in the Treating to New Targets (TNT), Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL), and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials (patient-level data) randomized to a statin arm (atorvastatin 80 mg/10 mg or simvastatin 20 mg) were chosen. Patients were divided into groups based on attained LDL-C levels (≤70 vs >70 mg/dL) and percent LDL-C reduction (≥50% vs <50%). Primary outcome was major cardiovascular event defined as death due to coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1 statin dose; Step 2 add attained LDL-C levels (continuous variable); Step 3 add percent LDL-C reduction (continuous variable). Model 2: Steps 2 and 3 were reversed.Results: Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (global chi-square increased from 3.64 to 26.1 to 47.5; P <.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (global chi-square increased from 3.64 to 47.5 to 47.5; P <.0001 and .94, respectively). Among patients with attained LDL-C ≤70 mg/dL, those with percent LDL-C reduction of <50% had a significantly higher risk of primary outcome (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.16-1.97; P = .002) and stroke (HR, 2.07; 95% CI, 1.46-2.93; P <.0001) and a numerically higher risk of death (HR, 1.37; 95% CI, 0.98-1.90; P = .06) when compared with the group with percent LDL-C reduction of ≥50%.Conclusions: In patients with atherosclerotic cardiovascular disease, percent LDL-C reduction provides incremental prognostic value over statin dose and attained LDL-C levels. However, the attained LDL-C level does not provide additional prognostic value over statin dose and percent LDL-C reduction. [ABSTRACT FROM AUTHOR]

Abstract: Objective: : To assess the discrepancies between LDL-cholesterol and apo B targets in patients at risk for vascular disease; namely, those with diabetes or hypertriglyceridemia and those with triglycerides &#60;1.7 mmol/L and normal glucose homeostasis. Methods: : Lipid clinic patients were divided into two groups: Group 1 consisted of 182 patients whose triglyceride levels were >1.7 mmol/L or who had impaired fasting glucose or type 2 diabetes. In Group 2, there were 42 patients with triglycerides &#60;1.7 mmol/L and normal glucose homeostasis. LDL-cholesterol and apo B were estimated during lipid clinic visits with patients on appropriate lipid lowering therapy. Results: : 46% of the patients in Group 1 who reached the high risk LDL-cholesterol target of &#60;2.5 mmol/L did not reach apo B target of &#60;0.9 g/L, while in Group 2, only 19% of those who reached the LDL-cholesterol target had apo B >0.9g/L. Conclusion: : Our findings demonstrate that a large percentage of patients with hypertriglyceridemia or impaired glucose tolerance, treated with lipid lowering agents, reach the LDL-cholesterol but not the apo B treatment targets. [Copyright &y& Elsevier]