Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 9 appraisals
The American journal of cardiology
Efficacy and Safety of Olezarsen for the Management of Dyslipidemia: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
This updated systematic review and meta-analysis evaluated the efficacy and safety of olezarsen in patients with dyslipidemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing olezarsen with placebo. Seven trials (n = 2,121) were included. Olezarsen significantly reduced triglycerides (mean difference [MD] -59.20 mg/dL), very-low-density lipoprotein cholesterol (MD -52.68 mg/dL), apolipoprotein B (MD -10.74 mg/dL), non-HDL cholesterol (MD -17.06 mg/dL), and apolipoprotein C-III (MD -64.16 mg/dL), and increased HDL cholesterol (MD 30.97 mg/dL), with no significant effect on LDL cholesterol. Injection site reactions (risk ratio [RR] 3.93) and platelet counts <140,000/µL (RR 4.76) were increased, whereas serious adverse events and significant liver enzyme elevations were comparable to placebo. Certainty of evidence ranged from moderate to low. In conclusion, olezarsen produces substantial improvements in triglyceride-rich lipoproteins with an acceptable safety profile; long-term cardiovascular outcome trials are warranted.
16 June 2026
Read appraisal →BMJ open
Effect of a culturally adapted heart-healthy diet with phytosterols and/or krill oil on lipid-related outcomes in familial hypercholesterolaemia: protocol for a multicentre randomised controlled trial in Brazil
INTRODUCTION: An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria. METHODS AND ANALYSIS: The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026. ETHICS AND DISSEMINATION: This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public. TRIAL REGISTRATION NUMBER: NCT06331195.
14 June 2026
Read appraisal →European journal of clinical pharmacology
Efficacy and safety of Ongericimab in patients with hypercholesterolemia: a systematic review and meta-analysis
BACKGROUND: Hypercholesterolemia represents abnormally elevated cholesterol levels and constitutes a major modifiable risk factor for cardiovascular diseases (CVDs). Low-density lipoprotein cholesterol (LDL-C) reduction remains the primary therapeutic target. However, many high-risk patients fail to achieve recommended LDL-C targets with conventional lipid-lowering therapies. Ongericimab is a new humanized recombinant monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). We aimed to evaluate the efficacy and safety of Ongericimab compared to placebo in patients with hypercholesterolemia. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Cochrane Library, Web of Science and Google Scholar through February 2025 for randomized controlled trials (RCTs) comparing Ongericimab versus placebo. Outcomes were pooled as mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) using random-effects models. RESULTS: Five RCTs comprising 1421 patients were included. Ongericimab significantly reduced LDL-C across all dosing regimens: 150 mg every 2 weeks (MD -69.48%, 95% CI: -73.02 to -65.94), 300 mg every 4 weeks (MD -61.82%, 95% CI: -66.66 to -56.98), and 450 mg every 4 weeks (MD -73.11%, 95% CI: -89.56 to -56.65); all p < 0.00001. Significant reductions were also observed in lipoprotein(a) (MD range: -44.81% to -50.06%), apolipoprotein B, non-HDL cholesterol, triglycerides, and total cholesterol, along with significant increases in HDL cholesterol and apolipoprotein A1. Adverse event rates were comparable between groups, with a pooled reduction OR of 0.85 (95% CI: 0.73-0.99) for overall treatment-emergent adverse events, favoring Ongericimab. CONCLUSION: This meta-analysis demonstrates that Ongericimab is effective and safe for improving lipid parameters in patients with hypercholesterolemia and dyslipidemia. These findings support Ongericimab as a valuable therapeutic option for patients requiring additional LDL-C reduction beyond conventional therapy. Further long-term studies are recommended to confirm cardiovascular outcomes.
28 May 2026
Read appraisal →Journal of the American Heart Association
Effect of Different Types of Whole Dietary Pulses on Established Therapeutic Lipid Targets for Cardiovascular Risk Reduction: An Updated Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials
BACKGROUND: Although dietary pulses are recognized by major clinical practice guidelines to reduce cholesterol and coronary heart disease risk, intake is low. There are no health claims for any pulse for cholesterol reduction, which could support uptake. We therefore conducted a systematic review and dose-response meta-analysis of randomized trials of the effect of different types of whole dietary pulses on lipid targets. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through March 2025 for trials ≥3 weeks. The primary outcome was low-density lipoprotein-cholesterol. Secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Thirty-eight trials (52 trial comparisons, n=2095) with a median of 6 weeks and dose of 130 g/d (0.5-0.67 cup/d) showed that whole dietary pulses decreased low-density lipoprotein-cholesterol (mean difference, -0.14 mmol/L [95% CI, -0.19 to -0.08]), non-high-density lipoprotein-cholesterol (-0.22 mmol/L [95% CI, -0.30 to -0.14]), apoB (apolipoprotein B) (-0.08 g/L [95% CI, -0.13 to -0.03]) and high-density lipoprotein-cholesterol (-0.03 mmol/L [95% CI, -0.05 to -0.01]) with no effects on other lipids. Analyses by pulse type showed similar results. A linear inverse relationship was shown for beans up to 1 cup/d for low-density lipoprotein-cholesterol (coefficient, -0.25 mmol/L/0.5 cup [95% CI, -0.48 to -0.02]) and non-high-density lipoprotein-cholesterol (-0.45 mmol/L/0.5 cup [95% CI, -0.71 to -0.18]). Grading of Recommendations Assessment, Development, and Evaluation was moderate-to-high for all outcomes, except apoB (very low). CONCLUSIONS: Whole dietary pulses likely result in small important-to-moderate reductions in lipid targets and trivial reductions in high-density lipoprotein-cholesterol. Similar effects were observed across pulse types with an inverse dose-response gradient for beans up to 1 cup/d. Future studies on chickpeas, dried peas, and lentils are warranted. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023432826; Unique identifier: CRD42023432826.
20 May 2026
Read appraisal →Circulation
Effect of APOC3 Inhibition With Olezarsen on Coronary Atherosclerosis: Essence-TIMI 73b Imaging Study
BACKGROUND: Whether lowering triglyceride-rich lipoproteins and remnant cholesterol favorably modifies coronary atherosclerosis is unclear. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL (low-density lipoprotein) cholesterol (LDL-C), and reduces apoB (apolipoprotein B) by ~15% in moderate hypertriglyceridemia. We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia. METHODS: We conducted a coronary computed tomography angiography study within Essence-TIMI 73b, a randomized, placebo-controlled trial of olezarsen versus placebo that enrolled patients between November 2022 and February 2024. Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence of or high risk for cardiovascular disease, and, for this imaging study, noncalcified plaque on baseline coronary computed tomography angiography. The primary end point was percent change from baseline to 12 months in noncalcified plaque volume. RESULTS: Of 468 participants (349 olezarsen, 119 placebo), the median age was 63 years (interquartile range, 56-70); 31% were women, and 97% received lipid-lowering therapy. Median baseline triglycerides were 249 mg/dL (interquartile range, 197-331), and remnant cholesterol was 53 mg/dL (interquartile range, 38-76). Median baseline noncalcified plaque volume was 125.3 mm³ (interquartile range, 63.2-213.3). At 6 months, olezarsen reduced triglycerides by 63.9%, remnant cholesterol by 71.9%, and apoB by 16.0% over placebo, with no difference in LDL-C. The percent change in noncalcified plaque volume from baseline to month 12 did not differ between olezarsen and placebo (placebo-adjusted least-squares mean difference, 2.98% [95% CI, -3.4 to 9.3]; p=0.36). No significant differences between olezarsen and placebo were observed for changes in low-attenuation, calcified, or total plaque volumes at 12 months. CONCLUSIONS: Despite substantial triglyceride and remnant cholesterol lowering, treatment with olezarsen for 12 months on top of standard-of-care lipid-lowering therapy in patients with largely moderate hypertriglyceridemia did not affect noncalcified coronary plaque volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05610280.
19 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
When bad turns good: a systematic review on cholesterol and LDL in longitudinal patient cohorts with Parkinson's disease
BACKGROUND: While the aetiology of Parkinson's disease (PD) involves genetic and environmental factors, emerging evidence has suggested a surprising link between lipid metabolism - particularly serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) - and the pathogenesis of PD. Cholesterol plays a vital role in neuronal membrane integrity, myelination, and synaptic function. However, its peripheral concentration and regulatory mechanisms in the central nervous system (CNS), remain incompletely understood in the context of PD. OBJECTIVE: This review aims to systematically examine the current literature on the relationship between TC and LDL-C with the risk and progression of PD in longitudinal patient cohorts. METHODS: A systematic literature search was conducted using PubMed with the keywords "Parkinson's disease" AND "cholesterol" and "Parkinson's disease" AND "LDL." Inclusion criteria encompassed English-language longitudinal human studies published before October 2024, with data on cholesterol levels in relation to PD incidence or progression. Fourteen studies met the eligibility criteria. RESULTS: Twelve of the 14 included studies reported an inverse association between lower serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and increased risk for PD onset as well as faster disease progression. Notably, this pattern was not uniform across all subgroups: age, sex, BMI, and statin use modulated the strength and direction of associations. CONCLUSION: Despite some heterogeneity across studies, there is growing evidence that lower TC and LDL-C may be associated with a higher risk and more rapid progression of PD. Future research should focus on mechanistic studies and stratified analyses to clarify whether and how cholesterol modulation could contribute to neuroprotective strategies in PD.
15 May 2026
Read appraisal →Journal of the American College of Cardiology
Cardiovascular Science, Medicine, and Society: The Brave New World: The ACC Braunwald Lecture 2025
Recent scientific and technological advances have dramatically expanded the possibilities in cardiovascular medicine. Landmark clinical trials have introduced transformative therapies for lipid disorders, heart failure, and obesity, offering clinicians powerful new tools to manage increasingly complex patient populations. Discoveries in molecular medicine, including gene therapies and RNA therapeutics, have ushered in new biopharmaceutical platforms and promise the potential for curative or infrequent dosing regimens. Minimally invasive, percutaneous, and robotic surgical techniques, along with next-generation devices and interventional procedures, are enhancing patient outcomes and broadening access to advanced care. The rapid rise of artificial intelligence and digital health technologies is reshaping how we gather, interpret, and act on data across the care continuum. Together, these developments mark the arrival of a brave new world in cardiovascular medicine. Yet the promise of this new era is tempered by unequal access, ethical dilemmas, and potential unintended consequences at both the patient and societal levels. This review is written in honor of Dr Eugene Braunwald, who has been a pioneer in cardiovascular science and technological innovation. The paper summarizes recent milestones in cardiovascular medicine and offers a forward-looking perspective on how to realize the full potential of innovation by translating scientific progress into equitable, responsible care and improved health outcomes.
25 Apr 2026
Read appraisal →The New England journal of medicine
Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease
BACKGROUND: Despite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited. METHODS: In this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years. Safety was also assessed. RESULTS: Of 3048 patients who underwent randomization, 1526 were assigned to the intensive-targeting group and 1522 to the conventional-targeting group. The median follow-up was 3.0 years. The median LDL cholesterol level during the trial was 56 mg per deciliter (1.4 mmol per liter) in the intensive-targeting group and 66 mg per deciliter (1.7 mmol per liter) in the conventional-targeting group. A primary end-point event occurred in 100 patients (Kaplan-Meier estimate of cumulative incidence, 6.6%) in the intensive-targeting group and in 147 patients (Kaplan-Meier estimate of cumulative incidence, 9.7%) in the conventional-targeting group (hazard ratio, 0.67; 95% confidence interval, 0.52 to 0.86; P = 0.002). The incidence of prespecified safety end points was similar in the two trial groups, except for a lower incidence of creatinine elevation in the intensive-targeting group. CONCLUSIONS: Among patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter. (Funded by the Cardiovascular Research Center and Yuhan; Ez-PAVE ClinicalTrials.gov number, NCT04626973.).
9 Apr 2026
Read appraisal →Current opinion in lipidology
Machine learning to predict elevated lipoprotein(a).
PURPOSE OF REVIEW: Lipoprotein(a), Lp(a), is a genetically determined, lifelong risk factor for atherosclerotic cardiovascular disease (ASCVD). Despite broad guideline support for universal one-time testing, Lp(a) measurement remains rare in clinical practice. This review summarizes recent advances in machine learning-based strategies that can enhance the efficiency, yield, and equity of Lp(a) screening. RECENT FINDINGS: To date, three studies have developed and validated machine learning models to identify individuals with elevated Lp(a) using routinely available clinical variables. The ARISE framework, derived from the UK Biobank and validated across multiple US cohorts, reduced the number needed to test by more than 50% while maintaining consistent discrimination across demographic subgroups. Additional studies have confirmed the feasibility of decision-tree and neural network models to improve case finding for elevated Lp(a) in both clinical and population-based settings. SUMMARY: Machine learning-based strategies provide a scalable means of operationalizing universal Lp(a) testing recommendations within health systems. When developed using unbiased data, externally validated, and assessed for fairness and interpretability, these models can support systematic identification of individuals with elevated Lp(a) and integration of Lp(a) measurement into routine cardiovascular risk assessment.
4 Apr 2026
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