Cardiac output in patients with small annuli undergoing transcatheter aortic valve implantation with self-expanding versus balloon expandable valve (COPS-TAVI).

BACKGROUND: There is limited data on cardiac output in patients with small aortic annuli undergoing trans-catheter aortic valve implantation (TAVI) according to the implanted platform of balloon-expandable (BEV) compared to self-expanding valves (SEV). METHODS: This is a retrospective analysis of consecutive patients with severe aortic stenosis and small annuli who underwent successful TAVI. Cardiac output was measured using echocardiography within 4 weeks following TAVI. Data were recorded and analysed by an experienced operator who was not aware of the type of the implanted valve. RESULTS: 138 patients were included in the analysis, of whom 57 % underwent TAVI with BEV. Clinical and echocardiographic characteristics were comparable between the two platforms, except for more frequent previous cardiac surgery and smaller indexed aortic valve in the BEV group. There was no relationship between computed tomography-derived aortic annulus area and cardiac output post TAVI. When compared to patients who underwent TAVI with BEV, those with SEV had larger cardiac output [mean difference - 0.50 l/min, 95 % CI (-0.99, -0.01)] and cardiac index [mean difference - 0.20 l/min/m2, 95 % CI (-0.47, 0.07)], although the latter did not reach statistical significance. Unlike patients with small body surface area, in those with large body surface area both cardiac output and cardiac index were statistically larger in patients who underwent SEV compared to BEV. CONCLUSION: Cardiac output, as measured by echocardiography, was larger in patients with small annuli who underwent TAVI procedure with SEV compared to BEV. Such difference was more evident in patients with large body surface area.

Positive Predictive Value of Computerized Tomography Coronary Angiography versus Computerized Tomography Fractional Flow Reserve in a Real-world Population.

Background: Computed Tomography coronary angiography and fractional flow reserve (CTCA and CT-FFR) are noninvasive diagnostic tools for the detection of flow-limiting coronary artery stenoses. Although their negative predictive values are well established, there is a concern that the high sensitivity of these tests may lead to overestimation of coronary artery disease (CAD) and unnecessary invasive coronary angiography (ICA). We compared the positive predictive value (PPV) of CT-FFR with computerized tomography coronary angiography (CTCA) against the gold standard of ICA in different real-world patient groups. Methods: A retrospective analysis of 477 patients referred for CTCA or CT-FFR for investigation of possible coronary ischemia. Patients were excluded if the image quality was poor or inconclusive. Patient-based PPV was calculated to detect or rule out significant CAD, defined as more than 70% stenosis on ICA. A sub-analysis of PPV by indication for the scan was also performed. Patients who underwent invasive nonhyperemic pressure wire measurements had their instant wave-free ratio or resting full-cycle ratio compared with their CT-FFR values. Results: In a patient-based analysis, the overall PPV was 59.3% for CTCA and 76.2% for CT-FFR. This increased to 81.0% and 86.7%, respectively, for patients with stable angina symptoms. In patients with atypical angina symptoms, CT-FFR considerably outperformed CTCA with a PPV of 61.3% vs. 37.5%. There was not a linear relationship between invasive pressure wire measurement and CT-FFR value (r = 0.23, P = 0.265). Conclusion: The PPV of CTCA and CT-FFR is lower in the real world than in previously published trials, partly due to the heterogeneity of indication for the scan. However, in patients with typical angina symptoms, both are reliable diagnostic tools to determine the presence of clinically significant coronary stenoses. CT-FFR significantly outperforms CTCA in patients with more atypical symptoms and the targeted use of CT-FFR in this group may help to avoid unnecessary invasive procedures.

The role of gender in resting full-cycle ratio (RFR) guided coronary revascularization.

BACKGROUND: Gender-based differences in clinical outcomes of patients undergoing fractional flow reserved (FFR) guided coronary revascularization is well documented. This study aimed to compare resting full-cycle ratio (RFR) values between men and women and whether this translated into difference in clinical outcomes in patients who underwent RFR-guided coronary revascularization. METHODS: This was a retrospective single-centre study of consecutive patients who underwent RFR-guided revascularization for coronary lesions with intermediate degree of stenosis. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), unplanned revascularization, and unstable angina requiring hospital admission at one year. RESULTS: In 373 consecutive patients (510 lesions, 26% women) there was no statistically significant difference in RFR value between men and women (0.90 ± 10 versus 0.90 ± 11, P = 0.95). There was no statistically significant difference between men and women in the primary endpoint, even after adjustment to the imbalance between the two groups [3.7% vs. 3.0%; HR 1.43, 95% CI (0.46 to 4.43), P = 0.54]; or its individual components of death (1.1% vs 0.8%, P = 0.76), MI (1.9% vs 0.8%, P = 0.38) or unplanned revascularization, including unstable angina admissions (2.6% vs 2.3%, P = 0.82). The comparable clinical outcomes were consistent across all different subgroups, including clinical presentation, diabetes status, left ventricle systolic function, kidney function, and the interrogated coronary artery. CONCLUSION: Our study suggests no significant gender-based difference in the value of RFR or 1-year clinical outcomes in patients undergoing resting physiology guided coronary revascularization.

Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment. METHODS AND RESULTS: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056). CONCLUSIONS: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.

The Use of Thrombectomy during Primary Percutaneous Coronary Intervention: Resurrecting an Old Concept in Contemporary Practice.

Optimal myocardial reperfusion during primary percutaneous coronary intervention (pPCI) is increasingly recognized to be beyond restoring epicardial coronary flow. Both invasive and non-invasive tools have highlighted the limitation of using this metric, and more efforts are focused towards achieving optimal reperfusion at the level of the microcirculation. Recent data highlighted the close relationship between thrombus burden and impaired microcirculation in patients presenting with ST-segment elevation myocardial infarction (STEMI). Moreover, distal embolization was an independent predictor of mortality in patients with STEMI. Likewise, the development of no-reflow phenomenon has been directly linked with worse clinical outcomes. Adjunctive thrombus aspiration during pPCI is intuitively intended to remove atherothrombotic material to mitigate the risk of distal embolization and the no-reflow phenomenon (NRP). However, prior trials on the use of thrombectomy during pPCI did not support its routine use, with comparable clinical endpoints to patients who underwent PCI alone. This article aims to review the existing literature highlighting the limitation on the use of thrombectomy and provide future insights into trials investigating the role of thrombectomy in contemporary pPCI.

Atherosclerosis Residual Lipid Risk-Overview of Existing and Future Pharmacotherapies.

Patients with atherosclerotic disease remain at increased risk of future events despite receiving optimal medical treatment. This residual risk is widely heterogeneous, but lipoprotein particles and their content play a major role in determining future cardiovascular events. Beyond low-density lipoprotein cholesterol (LDL-c), other lipoprotein particles have not demonstrated similar contribution to the progression of atherosclerosis. Statins, ezetimibe, and more recently, proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors and bempedoic acid have confirmed the causal role of LDL-c in the development of atherosclerosis. Data on high-density lipoprotein cholesterol (HDL-c) suggested a possible causal role for atherosclerosis; nonetheless, HDL-c-raising treatments, including cholesteryl-ester transfer protein (CETP) inhibitors and niacin, failed to confirm this relationship. On the other hand, mendelian randomisation revealed that triglycerides are more implicated in the development of atherosclerosis. Although the use of highly purified eicosapentaenoic acid (EPA) was associated with a reduction in the risk of adverse cardiovascular events, this beneficial effect did not correlate with the reduction in triglycerides level and has not been consistent across large phase 3 trials. Moreover, other triglyceride-lowering treatments, such as fibrates, were not associated with a reduction in future cardiovascular risk. Studies assessing agents targeting angiopoietin-like 3 (lipoprotein lipase inhibitor) and apolipoprotein C3 antisense will add further insights into the role of triglycerides in atherosclerosis. Emerging lipid markers such as lipoprotein (a) and cholesterol efflux capacity may have a direct role in the progression of atherosclerosis. Targeting these biomarkers may provide incremental benefits in reducing cardiovascular risk when added to optimal medical treatment. This Review aims to assess available therapies for current lipid biomarkers and provide mechanistic insight into their potential role in reducing future cardiovascular risk.

Bicuspid Aortic Valve Disease: Classifications, Treatments, and Emerging Transcatheter Paradigms.

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches.

Cognitive impairment and outcomes in older adults with non-ST-elevation acute coronary syndrome.

OBJECTIVE: This study aimed to explore the prognostic impact of cognitive impairment on the long-term risk of major adverse cardiovascular events (MACEs) in older patients with non-ST-elevation acute coronary syndrome (NSTEACS) undergoing invasive treatment. METHODS: Patients aged ≥75 years with NSTEACS undergoing an invasive strategy were included in the multicentre prospective study (NCT01933581). Montreal Cognitive Assessment was used to evaluate cognitive status at baseline (scores ≥26 classified as normal, <26 as cognitive impairment). Long-term follow-up data were obtained from electronic patient care records. The primary endpoint was MACE as a composite of all-cause deaths, reinfarction, stroke/transient ischaemic attack, urgent revascularisation and significant bleeding. RESULTS: 239 patients with baseline cognitive assessment completed long-term follow-up. Median age was 80.9 years (IQR 78.2-83.9 years) and 62.3% were male. On 5-year follow-up, there was no significant difference in the occurrence of MACE between the cognitively impaired group and the normal cognition group (p=0.155). Cognition status was not associated with MACE (HR 1.37 (95% CI 0.96 to 1.95); p=0.082). However, there was significantly more deaths (p=0.005) in those with cognitive impairment. Kaplan-Meier survival analysis (log-rank p=0.003) and Cox regression analysis (aHR 1.85 (95% CI 1.11 to 3.08); p=0.018) revealed increased risk of all-cause mortality, even after adjusting for frailty and GRACE (Global Registry of Acute Coronary Events) score. CONCLUSION: Cognitive impairment in older patients with NSTEACS undergoing an invasive strategy was associated with long-term all-cause mortality. Routine cognitive screening may aid risk stratification and further studies are needed to identify how this should influence management strategies and individual decision-making in this patient group. TRIAL REGISTRATION NUMBER: NCT01933581.

A case series of novel technique of coronary protection for patients with low coronary height undergoing transcatheter aortic valve implantation.

OBJECTIVE: Coronary artery occlusion (CAO) in patients undergoing transcatheter aortic valve implantation (TAVI) is rare but is associated with up to 50% mortality risk. We report a case series of a novel technique of coronary protection for patients undergoing TAVI at high risk of CAO. METHODS: Patients with symptomatic severe aortic stenosis scheduled for TAVI and at high risk of CAO were included. A noncompliant coronary angioplasty balloon was placed between the left coronary artery and the transcatheter heart valve. The distal "nose" of the balloon was positioned at the ostium of the left main and its main body "hanging" in the aorta. The coronary balloon was sized 1:1 to the left main, and simultaneous kissing balloon inflation was performed during valve deployment. RESULTS: Eight patients were included in this series. Five patients had previous isolated surgical bioprosthetic valves. The median left coronary height was 7.1 (6.0-8.4) mm with a median valve-to-coronary (VTC) distance of 3.3 (2.9-3.6) mm. There were no procedural complications, but one patient had a stroke during their in-hospital stay. After a median follow up of 12 (5.8-16.8) months, there were no mortality or rehospitalization events. CONCLUSION: Simultaneous kissing balloon is a novel technique of coronary protection in patients undergoing TAVI at high risk of CAO. Further studies are required to establish the safety of this novel technique.

A tale of tears and healing.

A 78-year-old woman with a background of hypertension and osteoarthritis presented with a history of syncope secondary to severe aortic stenosis. She underwent a computed tomography (CT) scan that showed a heavily calcific trileaflet aortic valve.

Microvascular Obstruction in Acute Myocardial Infarction, a Potential Therapeutic Target.

Microvascular obstruction (MVO) is a recognised phenomenon following mechanical reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Invasive and non-invasive modalities to detect and measure the extent of MVO vary in their accuracy, suggesting that this phenomenon may reflect a spectrum of pathophysiological changes at the level of coronary microcirculation. The importance of detecting MVO lies in the observation that its presence adds incremental risk to patients following STEMI treatment. This increased risk is associated with adverse cardiac remodelling seen on cardiac imaging, increased infarct size, and worse patient outcomes. This review provides an outline of the pathophysiology, clinical implications, and prognosis of MVO in STEMI. It describes historic and novel pharmacological and non-pharmacological therapies to address this phenomenon in conjunction with primary PCI.

Clinical outcomes of coronary intravascular lithotripsy in patients with stent failure (COIL registry).

BACKGROUND: Intravascular lithotripsy (IVL) has been demonstrated to be an effective treatment of calcified de novo coronary lesions. Safety data on the use of IVL within stented segments are lacking. We sought to evaluate the safety, feasibility, and long-term outcomes of IVL in patients with stent failure. METHODS: This was a retrospective multi-centre registry that included consecutive patients with stent failure who had undergone IVL treatment. The primary efficacy endpoint was procedural success defined as residual stenosis <30% (determined by quantitative coronary angiography analysis) in patients who survived hospital admission without in-hospital adverse events. Major adverse cardiovascular events (MACE) were defined as the composite endpoints of cardiovascular death, spontaneous myocardial infarction, and target vessel revascularisation at one-year follow up. RESULTS: 102 patients were included in this study. Mean age was 73 ± 9 years and 81% were male. The duration from previous stent implantation and IVL treatment was 24 (interquartile range 7-76) months, of which 10.8% received IVL for acute under-expanded stent. IVL treatment allowed significant improvement in both minimal lumen diameter (1.14 ± 0.60 to 2.53 ± 0.59, P < 0.001) and degree of stenosis (66.8 ± 19.9 to 20.3 ± 11.3%, P < 0.001). The rate of procedural success was 78.4% (80/102 of patients). The one-year MACE was 15.7%. Ostial disease (HR 5.16; 95% CI 1.19 to 22.33; P = 0.028) and lesion length (HR 1.05; 95% CI 1.01 to 1.10; P = 0.010) were independently associated with one-year MACE. CONCLUSIONS: In patients with stent failure, IVL is a safe and feasible treatment for this high-risk group.

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Complex Coronary Artery Disease: Long-term Clinical Outcomes from a High-volume Center.

Background: Clinical equipoise between a percutaneous coronary intervention (PCI) and coronary artery bypass grafting surgery (CABG) in the treatment of complex coronary artery disease (CAD), including unprotected left main coronary artery (LMCA) and/or three-vessel disease (3VD), remains debatable. Methods: A retrospective analysis of an unselected cohort undergoing contemporary PCI versus CABG at a large center in 2015. Patients who received nonemergent treatment of unprotected LMCA and/or 3VD were included. The primary study endpoint was all-cause mortality at 5 years. Secondary endpoints included a composite of all-cause mortality, spontaneous myocardial infarction (MI), or ischemia-driven repeat revascularization at 30 days and 1 year. Results: Four hundred and thirty patients met the inclusion criteria, 225 had PCI, and 205 had CABG. PCI patients were older with frequent LMCA involvement and higher EuroSCORE yet they had a fourfold shorter in-hospital stay compared to CABG patients. At 5 years, there was no significant difference in the primary endpoint between CABG and PCI (adjusted Hazard ratios 0.68, 95% confidence interval: 0.38-1.22, P = 0.19). Likewise, there was no significant difference in the incidence of the secondary composite endpoint or its components at 30 days or 1 year. A propensity score-matched analysis in 220 patients revealed similar outcomes. Conclusions: In real-world long-term contemporary data, survival after PCI was comparable to CABG at 5 years in patients with unprotected LMCA and/or 3VD. At 1 year, the incidence of spontaneous MI and ischemia-driven repeat revascularization did not differ between the two cohorts. The mode of revascularization in these complex patients should be guided by the heart team.

A Systematic Review and Meta-Analysis of the Clinical Outcomes of Isolated Tricuspid Valve Surgery.

Patients with isolated tricuspid valve (TV) disease have poor prognosis with no consensus on their management. Transcatheter TV intervention is emerging as a valid option in patients with prohibitive surgical risk. We analyzed studies of patients who underwent isolated TV surgery to identify the features associated with successful clinical outcomes. We performed a systematic review and meta-analysis of studies reporting clinical outcomes of isolated surgical TV intervention, namely TV repair, TV replacement with a bioprosthetic valve (TVR-B), or TV replacement with a mechanical valve (TVR-M). Twenty-seven studies involving 10,478 patients (4,931 TV repair, 3,821 TVR-B, and 1,713 TVR-M) were included. Early mortality occurred in 9% and did not differ between TV surgical approaches. Late mortality was 27% at a median follow-up of 4 (3 to 6) years and was significantly higher for all-TVR (30% vs 25%, rate ratio 1.18, 95% confidence interval 1.05 to 1.31, p = 0.004) and TVR-B (28% vs 24%, rate ratio 1.15, 95% confidence interval 1.02 to 1.30, p = 0.02) compared with TV repair. Late mortality did not differ between TVR-B and TVR-M. Across all studies, early complications included bleeding (7.4%), acute kidney injury (18.7%), permanent pacemaker (13.7%), cerebrovascular accidents (1.2%), and infection (8.9%). Late clinical outcomes included reintervention (3.7%), structural valve deterioration (2.4%), valve thrombosis (2.6%), and TV regurgitation recurrence after 1 year (15.0%). In conclusion, in isolated TV surgeries, TV repair has favorable long-term mortality compared with TV replacement. This supports the development and refinement of transcatheter TV repair approaches. Future research is recommended to provide comparative data for various transcatheter TV interventions.

Rotational atherectomy of left main stem immediately after transcatheter aortic valve implantation in a patient with symptomatic severe aortic stenosis and an impaired left ventricular systolic function: a case report.

Background: Severe aortic stenosis (AS) and coronary artery disease (CAD) often coexist since they both share the same risk factors and pathophysiology. Patients with severe AS with prohibitive surgical risk are often treated with transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) as a staged or concurrent procedure. Significant calcified CAD and left ventricular (LV) systolic impairment in such patients would add more challenges to the management. A clear consensus on the timing of revascularization of such patients in relation to the TAVI procedure is lacking. Case summary: Herein, we present an 86-year-old male who presented to a local district hospital with non-ST-segment elevation myocardial infarction (N-STEMI) and decompensated heart failure. His transthoracic echocardiography showed moderate LV systolic impairment with low-flow severe AS. He was initially treated with dual anti-platelet and diuretic therapy and subsequently underwent coronary angiography that revealed severe calcified shelf-like left main stem (LMS) and moderate left anterior descending (LAD) disease. He was successfully treated with TAVI and rotational atherectomy (RA)-assisted PCI to LMS and LAD in the same setting. Conclusion: There is limited evidence on effective strategies to tackle high-risk angioplasty with concurrent TAVI in patients with impaired LV function. We performed TAVI and RA to LMS and LAD in the same setting using no mechanical circulatory support (MCS). Management strategies should be individualized to highly selected patients taking into account LMS involvement, calcium modulation strategies, haemodynamic instability, or cardiogenic shock and whether MCS is needed.

Prospects for Precision Medicine in Acute Myocardial Infarction: Patient-Level Insights into Myocardial Injury and Repair.

The past decade has seen a marked expansion in the understanding of the pathobiology of acute myocardial infarction and the systemic inflammatory response that it elicits. At the same time, a portfolio of tools has emerged to characterise some of these processes in vivo. However, in clinical practice, key decision making still largely relies on assessment built around the timing of the onset of chest pain, features on electrocardiograms and measurements of plasma troponin. Better understanding the heterogeneity of myocardial injury and patient-level responses should provide new opportunities for diagnostic stratification to enable the delivery of more rational therapies. Characterisation of the myocardium using emerging imaging techniques such as the T1, T2 and T2* mapping techniques can provide enhanced assessments of myocardial statuses. Physiological measures, which include microcirculatory resistance and coronary flow reserve, have been shown to predict outcomes in AMI and can be used to inform treatment selection. Functionally informative blood biomarkers, including cellular transcriptomics; microRNAs; extracellular vesicle analyses and soluble markers, all give insights into the nature and timing of the innate immune response and its regulation in acute MI. The integration of these and other emerging tools will be key to developing a fuller understanding of the patient-level processes of myocardial injury and repair and should fuel new possibilities for rational therapeutic intervention.

Fractalkine Signalling (CX3CL1/CX3CR1 Axis) as an Emerging Target in Coronary Artery Disease.

Acute myocardial infarction (MI) is the most common and dramatic complication of atherosclerosis, which, despite successful reperfusion therapy, can lead to incident heart failure (HF). HF occurs when the healing process is impaired due to adverse left ventricular remodelling, and can be the result of so-called ischaemia/reperfusion injury (IRI), visualised by the development of intramyocardial haemorrhage (IMH) or microvascular obstruction (MVO) in cardiac MRI. Thus far, translation of novel pharmacological strategies from preclinical studies to target either IRI or HF post MI have been largely unsuccessful. Anti-inflammatory therapies also carry the risk of affecting the immune system. Fractalkine (FKN, CX3CL1) is a unique chemokine, present as a transmembrane protein on the endothelium, or following cleavage as a soluble ligand, attracting leukocyte subsets expressing the corresponding receptor CX3CR1. We have shown previously that the fractalkine receptor CX3CR1 is associated with MVO in patients undergoing primary PCI. Moreover, inhibition of CX3CR1 with an allosteric small molecule antagonist (KAND567) in the rat MI model reduces acute infarct size, inflammation, and IMH. Here we review the cellular biology of fractalkine and its receptor, along with ongoing studies that introduce CX3CR1 as a future target in coronary artery disease, specifically in patients with myocardial infarction.

Advances in Cardiovascular Pharmacology in Atherosclerotic-Related Therapeutic Areas: Addressing Patients' Clinical Needs.

Over the last three decades, a significant improvement has been achieved in reducing cardiovascular morbidity and mortality [...].

The Emerging Role of Icosapent Ethyl in Patients with Cardiovascular Disease: Mechanistic Insights and Future Applications.

Omega-3 polyunsaturated fatty acids (PUFAs) were early established as therapeutic option for patients with high triglyceride levels. Their effects on lipoprotein particles, including a reduction in very low-density lipoprotein and a shift from small to large low-density lipoprotein, is increasingly recognised. This is coupled with their ability to be incorporated within the cellular membrane, leading to plaque stability and anti-inflammatory effects. Nonetheless, recent clinical trials have not been consistent in demonstrating the potential cardioprotective effects of omega-3 fatty acids. This is despite the circumstantial evidence from imaging studies illustrating the stabilising effects on atherosclerotic plaques and slowing of plaque progression. In this article, we will review the effects of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on lipid biomarkers, atherosclerotic plaque features, and clinical outcome studies and provide a mechanistic role in managing residual risk of atherosclerosis. This will provide better insight into the inconsistency of the recently reported clinical outcome studies.