The CARUSO trial aims at investigating the efficacy of evolocumab in promoting carotid plaque morphological stabilization and regression as compared to traditional lipid lowering therapy (LLT). Primary end-point of the study is the superiority of evolocumab on top of ongoing LLT versus ongoing LLT in carotid plaque morphological stabilization and regression at 6 and 12 months, respectively. Secondary end-points are: LDL-Cholesterol (LDL-C) absolute and percentage changes in the two groups at 12 month follow-up, and adverse cerebrovascular and cardiac events at 12 and 24 months

Background Findings from clinical trials of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. Methods In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes. Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. (Funded by Amgen; EBBINGHAUS ClinicalTrials.gov number, NCT02207634 .).

The goal of this clinical trial is to evaluate the effect of evolocumab in combination with statin therapy (atorvastatin) in acute ischemic stroke (AIS).

The aim of the retrospective study is to characterize the molecular mechanisms responsible for the effect of statins and evolocumab in patients with stable coronary artery disease. The research team will retrieve and review intravascular imaging and gene expression data previously collected in the catheterization laboratory during the following time-period: 8/1/2013-4/14/2015 and 5/4/2021 - 10/28/2022.

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Background and Aims: Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, is indicated for the reduction of cardiovascular (CV) risk by lowering low-density lipoprotein cholesterol (LDL-C). We assessed the cost-effectiveness of evolocumab added to optimized standard of care (SoC), i.e. maximally tolerated statin with ezetimibe, in patients with Familial Hypercholesterolemia (FH) in Belgium. Methods: A previously published Markov model was adapted to the Belgian context. Patient characteristics, aligned with reimbursement criteria, were taken from a cohort of Belgian patients with FH. Baseline CV event (myocardial infarction, ischemic stroke, CV death) rates, utilities and costs were taken from published sources. The model used an evolocumab LDL-C reduction of 59%, as observed in the FOURIER trial, and the relationship between LDL-C lowering and CV event reduction from the Cholesterol Treatment Trialists’ Collaboration (CTTC) 2010 meta-analysis. An annual cost of evolocumab of €5,440 was utilized, based on its list price (before any potential discounts). Costs and health outcomes were evaluated over a lifetime horizon from payer perspective. Results: In primary prevention (PP) patients with FH and LDL-C ≥130 mg/dL, the incremental cost-effectiveness ratio (ICER) was €45,484. In secondary prevention (SP) patients with FH and LDL-C ≥100 mg/dL, the ICER was €36,627. In a combined PP (24%) and SP (76%) population, weighted according to evolocumab use observed in Belgium, the ICER was €38,770 (see table). [Formula presented] Conclusions: In Belgian patients with FH eligible for reimbursement, the addition of evolocumab to optimized SoC results in an ICER below generally accepted willingness-to-pay thresholds by Belgian authorities and may be considered cost-effective.

BACKGROUND:

With the rising burden of cardiovascular disease (CVD) and the need for cost-effective interventions, evaluating the economic implications of Evolocumab becomes crucial.

OBJECTIVES:

This study aimed to systematically review and evaluate the cost-effectiveness of Evolocumab in adults at risk of CVD.

METHODS:

We performed an extensive search in Cochrane Library, EMBASE, PubMed, ProQuest, and Web of Science. The reference lists of chosen literature reviews were also examined to find suitable cost-effectiveness analyses (CEAs) of Evolocumab in patients with CVD published until March 2023. The Consolidated Health Economic Evaluation Reporting Standards statement (CHEERS) was used to assess the reporting quality. Cost-related findings were adjusted to reflect 2023 purchase power parity (PPP) values in US dollars to enable cross-study comparisons.

RESULTS:

This systematic review comprised 16 studies, published between 2016 and 2023, mostly from the USA and China. Compliance with the CHEERS checklist was high in sections like abstracts, backgrounds, and objectives. However, areas like perspective (71.4%), time horizon (57.1%), and engagement with patients (14.3%) showed lower reporting rates. All studies evaluated the cost-effectiveness of Evolocumab in combination with other lipid-lowering treatments (LLTs). Notably, all studies employed model-based economic evaluations using a Markov cohort state-transition model, with a majority adopting a lifetime horizon. Most studies (10 cases) simultaneously reported both the Incremental Cost-Effectiveness Ratio (ICER) per Quality Adjusted Life Years (QALY) and the ICER per Life-Years Saved (LYS). Four studies exclusively reported ICER/QALY, and 2 studies solely focused on ICER/LYS. The ICER/ QALY exhibited a wide range (3,342.57 to 2,687,920.13 USD), with one study presenting as an outlier. Sensitivity analyses revealed factors influencing cost-effectiveness outcomes, including Low-Density Lipoprotein Cholesterol (LDL-C) levels, Evolocumab costs, and disease type, while several studies reported accepted thresholds for cost-effectiveness analysis.

CONCLUSIONS:

Our systematic review concludes that Evolocumab could be a cost-effective treatment, particularly for high-risk patient groups, but this varies by disease category, risk level, and evaluation methods. Future studies should investigate the economic impact's certainty and uncertainty, and consider different countries' income levels. LDL-C levels, medication costs, and CVD types are important factors affecting cost-effectiveness analysis.

Background: Direct comparisons between the drugs are limited, and the dosing remains debatable. Therefore, the study aims to indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis. Methods: Databases including PubMed, EMBASE, Web of Science, and the Cochrane Library were utilized to retrieve randomized controlled trials (RCTs). The search was conducted up to July 1, 2023. The Cochrane risk of bias tool was employed to appraise the quality of included studies. R software was used to conduct the Bayesian network meta-analysis. Results: Twenty-one RCTs with 10,835 patients were included. The network meta-analysis indicated that Evolocumab [mean difference (MD) = –60, 95% credibility interval (CrI) (–72, –49)] was the most effective (87%) in reducing low-density lipoprotein cholesterol (LDL-C), followed by alirocumab (71.4%) and inclisiran (47.2%), with placebo being the least effective (0.01%). In increasing high-density lipoprotein cholesterol (HDL-C), evolocumab [MD = 6.5, 95% CrI (3.2, 10)] ranked first (81.8%), followed by alirocumab (68.2%), with placebo again at the bottom (0.03%). In lowering total cholesterol, evolocumab [MD = –36, 95% CrI (–54, –19)] performed the best (86%), followed by alirocumab (64%), and placebo remained the least effective (0.04%). Regarding adverse events (AEs), evinacumab [odds ratio (OR) = 2, 95% CrI (1.17, 3.44)] ranked the highest (98.9%), followed by inclisiran (59.6%) and evolocumab (15.2%). Conclusions: Evolocumab appears to be the most effective in increasing HDL-C and reducing LDL-C and total cholesterol. Evinacumab shows the best safety profile with the lowest incidence of AEs. Copyright: © 2025 The Author(s).

BACKGROUND:

Evolocumab is a potent lipid-lowering drug that decreases plasma levels of lowdensity lipoprotein cholesterol (LDL-C) by 50-60%. FOURIER is a landmark randomized trial involving 27,564 patients with established cardiovascular disease already on statins and plasma LDLC levels > 70 mg/dl.

OBJECTIVE:

The main objective of FOURIER was to examine the effects of evolocumab on cardiovascular events.

RESULTS:

After a mean follow-up of 2.2 years, evolocumab significantly decreased the primary endpoint (composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) by 15% compared to placebo [hazard ratio 0.85 (95% CI, 0.79-0.92)], but no significant effect was found on mortality. The most common adverse effect of evolocumab was mild injection site reaction occurring in 2.1% of patients versus 1.6% of patients receiving placebo.

CONCLUSION:

These results support the use of evolocumab as add-on therapy to statins for high cardiac- risk patients not achieving optimal goals of LDL-C. Longer-term studies are needed to further clarify the efficacy and safety of evolocumab.

Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators\' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in patients with an ACS by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.