scholarly journals Time‐Dependent Cardiovascular Treatment Benefit Model for Lipid‐Lowering Therapies

2020 ◽  
Vol 9 (15) ◽  
Author(s):  
Irfan Khan ◽  
Eric D. Peterson ◽  
Christopher P. Cannon ◽  
Lauren E. Sedita ◽  
Jay M. Edelberg ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Time Dependent ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Treatment Benefit ◽  
Randomized Controlled ◽  
Lowering Therapy ◽  
Dependent Model ◽  
Time Dependent Model

Background With the availability of new lipid‐lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time‐dependent model from published randomized controlled trials summarizing the relationship between low‐density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. Methods and Results A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low‐density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time‐dependent model had better predictions than cholesterol treatment trialists’ estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high‐intensity statin, ezetimibe, and high‐dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high‐ or moderate‐intensity statin alone were achieved in higher‐risk populations with 2 to 5 years of treatment, and lower‐risk populations with 9 to 11 years of treatment. Conclusions The time‐dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid‐lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid‐lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.

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.

scholarly journals Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study

2020 ◽  
Vol 41 (40) ◽  
pp. 3900-3909 ◽  
Author(s):  
Ali Allahyari ◽  
Tomas Jernberg ◽  
Emil Hagström ◽  
Margrét Leosdottir ◽  
Pia Lundman ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Intensity ◽  
Low Density Lipoprotein ◽  
Monte Carlo Model ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Recent Myocardial Infarction ◽  
Lowering Therapy

Abstract Aims To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. Methods and results Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6–10 weeks after an MI event, 2013–17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target. Conclusion  Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.

scholarly journals GENetic characteristics and REsponse to lipid-lowering therapy in familial hypercholesterolemia: GENRE-FH study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyoeun Kim ◽  
Chan Joo Lee ◽  
Hayeon Pak ◽  
Doo-Il Kim ◽  
Moo-Yong Rhee ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Genetic Characteristics ◽  
Pathogenic Variants ◽  
Lowering Therapy ◽  
Primary Variable

Abstract Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R2 = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.

The role of bempedoic acid in the management of dyslipidaemia

2021 ◽  
Vol 3 (12) ◽  
pp. 484-488
Author(s):  
Beverley Bostock
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Technology Appraisal ◽  
The United Kingdom ◽  
Lipid Lowering Drug ◽  
Lowering Therapy ◽  
Lowering Drug

Bempedoic acid is a new oral lipid-lowering therapy which has been licenced for use in the United Kingdom. It can be used alone, with a statin, or with other lipid-lowering therapies where the target level for low density lipoprotein has not been achieved with these therapies alone. Bempedoic acid with ezetimibe can be prescribed for people who are unable to tolerate statins. This combination has received NICE approval following a technology appraisal. This paper discusses the place for of bempedoic acid as a lipid lowering drug and consider the mode of action, licensed indications, adverse drug reactions and the NICE technology appraisal recommendations.

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