scholarly journals Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges

Heart ◽  
2021 ◽  
pp. heartjnl-2020-318760
Author(s):  
Chris Packard ◽  
M John Chapman ◽  
Mahendra Sibartie ◽  
Ulrich Laufs ◽  
Luis Masana
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Evidence Base ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk ◽  
Intervention Trials ◽  
European Society Of Cardiology

Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of coronary heart disease and stroke. Guidelines for the management of dyslipidaemia from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were updated in late 2019 in light of recent intervention trials involving the use of innovative lipid-lowering agents in combination with statins. The new guidelines advocate achieving very low LDL-C levels in individuals at highest risk, within the paradigm of ‘lower is better’. With the advent of combination therapy using ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitors in addition to statins, the routine attainment of extremely low LDL-C levels in the clinic has become a reality. Moreover, clinical trials in this setting have shown that, over the 5–7 years of treatment experience to date, profound LDL-C lowering leads to further reduction in cardiovascular events compared with more moderate lipid lowering, with no associated safety concerns. These reassuring findings are bolstered by genetic studies showing lifelong very low LDL-C levels (<1.4 mmol/L; <55 mg/dL) are associated with lower cardiovascular risk than in the general population, with no known detrimental health effects. Nevertheless, long-term safety studies are required to consolidate the present evidence base. This review summarises key data supporting the ESC/EAS recommendation to reduce markedly LDL-C levels, with aggressive goals for LDL-C in patients at highest risk, and provides expert opinion on its significance for clinical practice.

Cardiovascular event rates increase after each recurrence and associate with poor statin adherence

2020 ◽  
pp. 204748732090433 ◽  
Author(s):  
Mariann I Lassenius ◽  
Iiro Toppila ◽  
Susanne Bergius ◽  
Julia Perttilä ◽  
KE Juhani Airaksinen ◽  
...  
Keyword(s):  
Cardiovascular Event ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk ◽  
Event Rates

Aims The study evaluated the quality of cardiovascular prevention in real-world clinical practice. The recurrence of up to five cardiovascular events was assessed, as data on recurrence beyond the first event and interindividual variations in event rates past the second event have been sparse. Low-density lipoprotein cholesterol concentrations and lipid-lowering therapy use were investigated. Methods This retrospective register-based study included adult patients with an incident cardiovascular event between 2004 and 2016 treated in the hospital district of southwest Finland. Patients were followed for consecutive cardiovascular events or cardiovascular death, low-density lipoprotein cholesterol and statin purchases. The timing of event recurrence was evaluated, and predictive factors were assessed. Results A wide interindividual variation in cardiovascular event recurrence was observed, each additional event caused an increased risk, the median time of recurrence decreased from 7 to one year for the second and fifth event. Event rates increased correspondingly from 12 to 43/100 patient-years and were most pronounced in the first years following the previous event. The low-density lipoprotein cholesterol goal (<1.8 mmol/l) was reached by 18% in the year after the event and statin underuse was associated with an increased risk of recurrence. Six months after the index event high intensity statins were used by only 22% of the cohort. Conclusion The study provides new perspectives on individual risk assessment showing that event rates are not stable for all patients but increase 1.2–1.9-fold per consecutive event. The underuse of statins and poor adherence support the identification of these patients for intensified multifactorial preventive measures.

scholarly journals Low-density Lipoprotein Cholesterol and Risk of Intracerebral Hemorrhage: A Prospective Study, Systematic Review, and Meta-analysis (P18-029-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chaoran Ma ◽  
M Edip Gurol ◽  
Zhe Huang ◽  
Alice Lichtenstein ◽  
Xiuyan Wang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Hemorrhagic Stroke ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk

Abstract Objectives To prospectively examine the association between low density lipoprotein cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk, and test the association in a meta-analysis combining the present data with previous studies. Methods The current cohort study included 96,043 participants (mean age 51.3 y), free of stroke, myocardial infarction, and cancer at baseline (2006). Serum LDL-C concentrations were assessed in 2006, 2008, 2010 and 2012. Cumulative average LDL-C concentrations were calculated from all available LDL-C data during that period. Incident ICH was confirmed by review of medical records. Results We identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70–99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations less than 70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70–99 mg/dL –adjusted HR 1.65 (95%CI, 1.32 to 2.05) for LDL-C concentrations of 50–69 mg/dL and 2.69 (95%CI, 2.03 to 3.57) for LDL-C concentrations of <50 mg/dL. In the meta-analysis of 11 prospective studies, the pooled HRs of hemorrhagic stroke for per 10 mg/dL decrement in LDL-C was 1.03 (95% CI, 1.01 to 1.06). Conclusions We observed a significant association between lower LDL-C and higher risk of ICH when LDL-C concentrations <70 mg/dL, and the risk decreased to a non-significance level and stabilized when LDL-C ≥70 mg/dL. These data can help determination of ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and also guide planning of future lipid lowering studies. Funding Sources Supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. Supporting Tables, Images and/or Graphs

scholarly journals U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiao Gong ◽  
Yaqiong Chen ◽  
Yusheng Jie ◽  
Mingkai Tan ◽  
Zhaofang Jiang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Odds Ratios ◽  
Lowering Therapy ◽  
Severe Group

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

Abstract P43: Frequency and Predictors of Low-Density Lipoprotein Cholesterol Control and Appropriate Response to Elevated LDL-C Levels in Patients with Cardiovascular Disease

2011 ◽  
Vol 4 (suppl_2) ◽  
Author(s):  
Salim S Virani ◽  
Lechauncy D Woodard ◽  
Supicha Sookanan ◽  
Cassie R Landrum ◽  
Tracy H Urech ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Medication Possession Ratio ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
To Receive

Background: Although current cholesterol performance measures define good quality as low density lipoprotein cholesterol (LDL-C) levels < 100mg/dl in cardiovascular disease (CVD) patients, they provide a snap shot at one time point and do not inform whether an appropriate action was taken to manage elevated LDL-C levels. We assessed frequency and predictors of this appropriate response (AR). Methods: We used administrative data to assess 22,902 CVD patients receiving care in a Veterans Affairs network of 7 hospitals and affiliated clinics. We determined the proportion of CVD patients at LDL-C goal <100 mg/dl, and the proportion of patients with uncontrolled LDL-C levels (>100 mg/dl) who had an AR [defined as the initiation or dosage increase of a lipid lowering medication (LLM), addition of a new LLM, receipt of maximum dosage or >1 LLM, or LDL-C reading <100 mg/dl] at 45 days follow-up. Logistic regression was performed to evaluate facility, provider and patient characteristics associated with AR. Results: LDL-C levels were at goal in 16,350 (71.4%) patients. An additional 2,110 (9.2%) had an AR at 45 days of follow-up. Controlling for clustering between facilities and patient's illness severity, history of diabetes (OR 1.18, 95% CI 1.03-1.35), hypertension (OR 1.21, 95% CI 1.02-1.44), patients showing good medication adherence (medication possession ratio > 0.8) [OR 2.29, 95% CI 1.99-2.64] were associated with AR. Older CVD patients (age >75 years) were less likely to receive AR (OR 0.60, 95% CI 0.52-0.70). Teaching vs. non-teaching facility (p=0.40), physician vs. non-physician provider (p=0.14), specialist vs. non-specialist primary care provider (p=0.12), and patient's race (p=0.12) were not predictors of AR. Conclusion: Among patients with CVD and LDL-C above guideline recommended levels, only one-third receive AR. Diabetic and hypertensive CVD patients are more likely to receive AR, whereas older Veterans with CVD receive AR less often likely reflecting providers' belief of lack of efficacy from treatment intensification in older CVD patients. Our findings are important for quality improvement and policy making initiatives as they provide more actionable information compared with isolated LDL-C goal attainment as a quality indicator.

Comparison of LDL-C calculation by friedewald and martin/hopkins methods in 12,243 adults from the United States of America

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Penson ◽  
S.S Martin ◽  
N.C Henney ◽  
M Banach
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Threshold Value ◽  
The United States ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Strongly Correlated ◽  
Low Density Lipoprotein Cholesterol

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and a target for lipid-lowering therapy. LDL-C is typically not measured directly but is estimated using the Friedewald formula, which assumes a fixed factor for the ratio of triglycerides (TG) to very low-density lipoprotein cholesterol (VLDL-C). However this assumption is sometimes not valid. The Martin/Hopkins (M/H) formula estimates LDL-C using an adjustable factor for the TG:VLDL-C ratio and is expected to improve upon Friedewald when predicting measured LDL-C, and apolipoprotein B (ApoB), one molecule of which is associated with each LDL particle. Purpose We compared values of LDL-C calculated by the Friedewald and M/H methods with respect to their correlation with non-high density lipoprotein cholesterol (non-HDL-C) and ApoB, and their classification of individuals based upon attainment of the threshold value of 70 mg/dl (1.8 mmol/l) of LDL-C. This cut-point is a treatment target for individuals at high risk of CVD in the 2019 ESC guidelines for lipid modification, and a threshold for initiating statin therapy in the 2019 ACC/AHA guidelines. Methods In this analysis we included participants in the National Health and Nutrition Examination Survey (NHANES) from 2005–2016, age ≥18, &lt;80 years who had measurements for total cholesterol (TC), TG and HDL-C. LDL-C was calculated using Friedewald and M/H. We correlated LDL-C (calculated using the two methods) with non-HDL-C and ApoB. We identified individuals with LDL-C &lt;70 mg/dl using both methods. When LDL-C (Friedewald) was &lt;70, but LDL-C (M/H) was &gt;70, we classified these participants as discordant. Statistical analyses were performed in IBM SPSS for Windows v26. Results 12,243 individuals were included. 51.8% were female, mean (±SD) age was 45.5±17.4, 15.3% were treated with statins, ApoB was available for 2179 participants. Mean lipid concentrations (mg/dl) were: TC: 191.5±41.0, TG: 120.0±67.0, HDL-C: 54.1±15.7, LDL-C (Friedewald): 113.3±35.4; LDL-C (M/H): 114.9±35.2. In the whole population, LDL-C (M/H) was more strongly correlated than LDL-C (Friedewald) with ApoB (r=0.935 v 0.894) and non-HDL-C (r=0.981 v 0.944). In statin-treated participants, LDL-C (M/H) was also more strongly correlated with ApoB (r=0.951 v 0.914) and non-HDL-C (r=0.979 v 0.928). 1139 participants had LDL-C (Friedewald) &lt;70 mg/dl. Of these, 206 individuals (18.1%) were discordant, having LDL-C (M/H) &gt;70 mg/dl. Amongst statin-treated patients, 22.9% were discordant. Only 5.5% of individuals with LDL-C (M/H) &lt;70 mg/dl showed reverse discordance (LDL-C (Friedewald) &gt;70 mg/dl). Conclusions The M/H method of calculating LDL-C correlates more strongly with non-HDL-C and ApoB than Friedewald. Importantly the discordant results confirm previous observations that Friedewald underestimates LDL-C at low concentrations. This may result in under-use of lipid-lowering therapies. Funding Acknowledgement Type of funding source: None

scholarly journals Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 254 ◽  
Author(s):  
Chih-Sheng Chu ◽  
Shi Hui Law ◽  
David Lenzen ◽  
Yong-Hong Tan ◽  
Shih-Feng Weng ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Clinical Significance ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Exercise Stress ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Despite the numerous risk factors for atherosclerotic cardiovascular diseases (ASCVD), cumulative evidence shows that electronegative low-density lipoprotein (L5 LDL) cholesterol is a promising biomarker. Its toxicity may contribute to atherothrombotic events. Notably, plasma L5 LDL levels positively correlate with the increasing severity of cardiovascular diseases. In contrast, traditional markers such as LDL-cholesterol and triglyceride are the therapeutic goals in secondary prevention for ASCVD, but that is controversial in primary prevention for patients with low risk. In this review, we point out the clinical significance and pathophysiological mechanisms of L5 LDL, and the clinical applications of L5 LDL levels in ASCVD can be confidently addressed. Based on the previously defined cut-off value by receiver operating characteristic curve, the acceptable physiological range of L5 concentration is proposed to be below 1.7 mg/dL. When L5 LDL level surpass this threshold, clinically relevant ASCVD might be present, and further exams such as carotid intima-media thickness, pulse wave velocity, exercise stress test, or multidetector computed tomography are required. Notably, the ultimate goal of L5 LDL concentration is lower than 1.7 mg/dL. Instead, with L5 LDL greater than 1.7 mg/dL, lipid-lowering treatment may be required, including statin, ezetimibe or PCSK9 inhibitor, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Since L5 LDL could be a promising biomarker, we propose that a high throughput, clinically feasible methodology is urgently required not only for conducting a prospective, large population study but for developing therapeutics strategies to decrease L5 LDL in the blood.

Statin-based therapy for primary and secondary prevention of ischemic stroke: A meta-analysis and critical overview

2019 ◽  
Vol 15 (4) ◽  
pp. 377-384 ◽  
Author(s):  
Haralampos Milionis ◽  
George Ntaios ◽  
Eleni Korompoki ◽  
Konstantinos Vemmos ◽  
Patrik Michel
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Primary And Secondary Prevention ◽  
Prevention Trials

Background and aims To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. Methods English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Results Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60–0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70–0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of “the lower the better” hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Conclusions Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.

scholarly journals Lipoproteins and other Risk Factors for Cardiovascular Disease in a Student Population

2013 ◽  
Vol 32 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Dragana Pap ◽  
Emina Čolak ◽  
Nada Majkić-Singh ◽  
Gordana Grubor-Lajšić ◽  
Sanja Vicković
Keyword(s):  
Risk Factors ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipid Status ◽  
Increased Risk ◽  
Group 2 ◽  
Group 1

Summary Background: Cardiovascular disease (CVD) is a major cause of mortality and morbidity in many populations, especially in developed countries. The aim of the study was to analyze the lipid status in a student population at increased risk for CVD in comparison with students who are not at increased risk for CVD. Methods: This study included 238 students from the University of Novi Sad of both sexes (126 men and 112 women), with a mean age of 22.32±1.85 years. According to the body mass index (BMI) lower and higher than 25 kg/m2 and waist circumference (WC) of less and more than 94 cm (80 cm for females) the whole group of 238 students was divided into 2 subgroups: the group at increased risk for CVD (Group 1) and the group at lower risk for CVD (Group 2). Total cholesterol - TCH, triglycerides - TG, high density lipoprotein cholesterol - HDL-c, low density lipoprotein cholesterol - LDL-c, very low-density lipoprotein cholesterol - VLDL-c concentrations were determined and the index of atherosclerosis (IA), established risk factors RF-TCH/HDL-c ratio and non-HDL-c/HDL-c ratio were mathematically calculated. Results: The values of TCH, LDL-c, non-HDL-c, VLDL-c and TG were significantly higher in Group 1 compared to Group 2 (P<0.001). IA, non-HDL-c/HDL-c and RF-TCH/HDL-c ratio were also significantly higher (P<0.001), while HDL-c was significantly lower (p<0.01) in Group 1 compared to controls. These results were not influenced by gender in both groups of subjects. Conclusions: The data suggest that increased anthropometric parameters are followed by increased lipoprotein status in the group of students at increased risk for CVD and screening of the lipid status is necessary in students, especially in those who are at increased risk for CVD.

Reduction in the Ratio of Low-density Lipoprotein Cholesterol to Highdensity Lipoprotein Cholesterol is Associated with Increased Risks of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

2019 ◽  
Vol 16 (3) ◽  
pp. 266-272 ◽  
Author(s):  
Yanan Wang ◽  
Chenchen Wei ◽  
Quhong Song ◽  
Junfeng Liu ◽  
Yajun Cheng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hemorrhagic Transformation ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Stroke Patients ◽  
Increased Risk

Background and Purpose: Hemorrhagic transformation (HT) is a potentially serious complication in patients with acute ischemic stroke (AIS). Whether the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) is associated with HT remains unclear. Methods: Ischemic stroke patients within 7 days of stroke onset from January 2016 to November 2017 were included in this study. Lipid profiles were measured within 24h after admission. HT was determined by a second computed tomography or magnetic resonance imaging within 7 days after admission. Univariate and multivariate logistic regression analysis was used to assess the association between LDL-C/HDL-C and HT. Results: We enrolled 1239 patients with AIS (788 males; mean age, 64 ± 15 years), of whom 129 (10.4%) developed HT. LDL-C/HDL-C was significantly lower on admission in patients with HT than those without HT (2.00 ± 0.89 vs. 2.25 ± 1.02, P=0.009). The unadjusted odds ratio (OR) of low LDL-C/HDL-C for HT was 2.07 (95% confidence interval [CI] 1.42-3.01, P＜0.001). After adjustment for possible confounders, lower LDL-C/HDL-C (≤1.52) was significantly associated with HT (OR 1.53, 95% CI: 1.02-2.31, P=0.046). Similar results were observed between lower LDL-C (≤ 4 mmol/L) and HT (OR 4.17, 95% CI: 1.25-13.90, P=0.02). However, no significant association was found between HT and high HDL-C, low triglycerides or low total cholesterol. Conclusion: Lower LDL-C/HDL-C and LDL-C were significantly associated with increased risk of HT after AIS. Further investigations are warranted to confirm these findings and then optimize lipid management in stroke patients with lower LDL/HDL-C or LDL-C.

Abstract 13503: Relative Efficacy of Alirocumab, Bempedoic Acid, Evolocumab, Ezetimibe and Inclisiran Added to Statins for Reduction of Low Density Lipoprotein Cholesterol - A Network Meta-Analysis of Randomized Clinical Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Peter P Toth ◽  
Sarah Bray ◽  
Gavin Worth
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Relative Efficacy ◽  
Low Density Lipoprotein Cholesterol

Background: Many patients with hypercholesterolemia and/or cardiovascular disease are unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) reduction with statins alone (or are statin intolerant). This is increasingly the case with clinical guidelines recommending that lower LDL-C levels are beneficial for patients. This network meta-analysis (NMA) assessed the relative efficacy of lipid lowering therapies (LLTs) added to statins for reducing LDL-C. Methods: A systematic review of randomized controlled clinical trials to May 2020 identified 48 studies for inclusion in the primary NMA. The primary NMA included studies ≥12 weeks duration in which alirocumab, bempedoic acid, evolocumab, ezetimibe, or inclisiran were added to moderate-high intensity statins (or lower intensity / no statin in statin intolerant patients). Random effects NMA was used to analyse % change in LDL-C to compare the treatment effects indirectly. Results: Over 12 weeks, all non-statin LLTs significantly reduced LDL-C from baseline versus placebo. Evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were associated with largest LDL-C reductions, which were greater than those achieved with lower/alternative doses of alirocumab, bempedoic acid (± ezetimibe), ezetimibe and inclisiran (Table). Consistent results were observed in sensitivity analyses to address heterogeneity (excluding familial hypercholesterolemia and east Asian studies), in the subgroup NMA of studies in predominantly atherosclerotic cardiovascular disease patients, and in the statin intolerant subgroup NMA. Conclusions: All agents reduced LDL-C, however, the PCSK9 inhibitors evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were the most effective LLT regimens for reducing LDL-C when added to statins.

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