Dataset Information

Additive effects of ezetimibe, evolocumab, and alirocumab on plaque burden and lipid content as assessed by intravascular ultrasound: A PRISMA-compliant meta-analysis.

ABSTRACT:

Background

The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear.

Methods

According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we performed a systematic review and meta-analysis of trials assessing the effects of ezetimibe, evolocumab, and alirocumab on coronary atherosclerosis using IVUS. The primary outcome was change in total atheroma volume (TAV), and the secondary outcomes were changes and differences in plaque composition and lipid content.

Results

Data were collected from 9 trials, involving 917 patients who received ezetimibe, evolocumab or alirocumab in addition to a statin and 919 patients who received statins alone. The pooled estimate demonstrated a significant reduction in TAV with the addition of ezetimibe and favorable effects of evolocumab and alirocumab on TAV. Subgroup analysis also supported favorable effects of evolocumab and alirocumab on TAV, according to baseline TAV, gender, type 2 diabetes mellitus, and prior stain use. Addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), but not in high-density lipoprotein cholesterol (HDL-C). The pooled estimate also showed significant favorable effects of ezetimibe on LDL-C, TC, and TG, but an insignificant effect on HDL-C. Patients who received ezetimibe showed similar changes in the necrotic core, fibro-fatty plaque, fibrous plaque, and dense calcification compared with patients not treated with ezetimibe.

Conclusions

The addition of ezetimibe to statin therapy may further reduce plaque and lipid burdens but may not modify plaque composition. Although current evidence supports a similar impact from the addition of PCSK9 inhibitors to statin therapy, more evidence is needed to confirm such an effect.

SUBMITTER: Liang D

PROVIDER: S-EPMC9575789 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Additive effects of ezetimibe, evolocumab, and alirocumab on plaque burden and lipid content as assessed by intravascular ultrasound: A PRISMA-compliant meta-analysis.

Liang Di D Li Chang C Tu Yanming Y Li Zhiyong Z Zhang Ming M

Medicine 20221001 41

<h4>Background</h4>The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear.<h4>Methods</h4>According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we performed a systematic review and meta-analysis of trials assessing the effects of ezetimibe, evolocumab, and alirocumab on coronary atherosclerosis using IVUS. The primary outcome was change in total ...[more]

PMID: 36254013

Similar Datasets

Project description:BackgroundDespite treatment with statins, dyslipidaemia patients with elevated cholesterol- and triglyceride-levels remain at high residual risk for major adverse cardiovascular events (MACE). New lipid-lowering drugs must prevent the occurrence of MACE and exhibit cost-effectiveness for their successful adoption to clinical practice.ObjectiveTo assess the cost effectiveness of icosapent ethyl, fenofibrate, ezetimibe, evolocumab, and alirocumab in combination with statins compared to statin monotherapy for cardiovascular prevention from the perspective of UK's National Health Service.MethodsA Markov model simulated the progression of cardiovascular disease and MACE, including myocardial infarction, stroke, angina pectoris, and coronary revascularisation, in dyslipidaemia patients. The model was populated with cardiovascular outcome trial data for each drug. Cost and utility data were extracted from peer-reviewed literature. The incremental cost-effectiveness ratio (ICER) is reported per quality-adjusted life years (QALY) gained in 2021 Great Britain Pounds (£).ResultsFor primary cardiovascular prevention, icosapent ethyl increased QALYs by 0.79 and costs by £15,421 compared to statin monotherapy (ICER = £19,485/QALY). Fenofibrate yielded 0.62 additional QALYs at cost-savings of - £6127 (ICER = - £9932/QALY). For secondary prevention, the omega-3 fatty acid icosapent ethyl extended QALYs by 0.98 at costs of £12,981 compared to statin monotherapy (ICER = £13,285/QALY). Fenofibrate added 0.85 QALYs whilst saving - £637 (ICER = - £7472/QALY). Ezetimibe increased QALYs by 0.60 at cost reductions of - £2529 (ICER = - £4231/QALY). PCSK9 inhibitors provided QALYs of 0.53 and 0.86 at costs of £45,279 and £46,375 for evolocumab (ICER = £85,193/QALY) and alirocumab (ICER = £54,211/QALY), respectively. At a willingness-to-pay threshold of £25,000/QALY, there is a probability of 100% for icosapent ethyl (98% in primary prevention) and 0% for PCSK9 inhibitors to be cost effective in secondary prevention.ConclusionsIcosapent ethyl is cost effective for primary and secondary cardiovascular prevention at an annual price of £2064 in the UK. For PCSK9 inhibitors, price discounts or prescription restrictions are necessary to achieve cost effectiveness.

Project description:BackgroundCardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability.MethodsTransthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score-matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive.ResultsPatients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification.ConclusionsThere is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).

Project description:BackgroundBaseline imbalances have been identified in randomized trials of evolocumab and alirocumab. Our aim was to quantitatively assess (1) the presence of systematic baseline differences, and (2) the relationship of baseline differences with effects on low-density lipoprotein-cholesterol (LDL-c) and clinical outcomes in the trials.MethodsWe performed a meta-epidemiological study. PubMed, Embase, regulatory reports, ClinicalTrials.gov and company websites were searched for trials. Seven baseline characteristics (mean age, LDL-c, BMI, percentage males, diabetics, smokers, and hypertensives) and five outcomes (LDL-c, major adverse cardiac events, serious adverse events, any adverse events, all-cause mortality) were extracted. We calculated (1) range and distribution of baseline imbalances (sign-test), (2) pooled baseline differences and heterogeneity (meta-analysis), (3) differences in SDs around continuous variables (sign-test and pooling), and (4) the relationship of baseline differences with outcomes (meta-regression). The comparisons of PCSK9-inhibitor groups with either placebo or ezetimibe were analysed separately and combined.ResultsWe identified 43 trials with 63,193 participants. Baseline characteristics were frequently missing. Many trials showed small baseline imbalances, but some large imbalances. Only baseline BMI showed a statistically significant lower pooled mean for the drug versus placebo groups (MD -0.16; 95% CI -0.24 to -0.09). Heterogeneity in baseline imbalances was present in six placebo- and five ezetimibe-comparisons. Heterogeneity was statistically significant for BMI, males, diabetics and hypertensives in the combined comparisons. There was a statistically significant preponderance for larger SDs in the PCSK9-inhibitor versus control groups (sign-test age 0.014; LDL-c 0.014; BMI 0.049). Meta-regression showed clinically relevant relationships of baseline imbalances in age, BMI and diabetics with the risk of any adverse events and the risk of mortality. Two relationships were statistically significant: A higher mean BMI in the drug versus control group with a decreased risk of mortality (beta - 0.56; 95% CI -1.10 to -0.02), and a higher proportion of diabetics with an increased risk of any adverse events (beta 0.02; 95% 0.01 to 0.04).ConclusionsHeterogeneous baseline imbalances and systematically different SDs were present in evolocumab and alirocumab trials, so study groups cannot be assumed to be comparable. These findings raise concerns about the design and conduct of the randomization procedures.

Dataset Information

Additive effects of ezetimibe, evolocumab, and alirocumab on plaque burden and lipid content as assessed by intravascular ultrasound: A PRISMA-compliant meta-analysis.

Background

Methods

Results

Conclusions

Publications

Additive effects of ezetimibe, evolocumab, and alirocumab on plaque burden and lipid content as assessed by intravascular ultrasound: A PRISMA-compliant meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets