Eliminate LDL cholesterol after heart attack but only for a while.

There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey post hoc analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; P = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; P < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.

Controversy in cardiology: clopidogrel or acetylsalicylic acid in the treatment of chronic coronary syndromes?

Secondary prevention of patients with chronic coronary syndrome is based on the long-term use of a single anti-aggregating drug which is traditionally represented by acetylsalicylic acid (ASA) in light of the results of studies and meta-analyses which have demonstrated a clear anti-ischaemic efficacy against of an acceptable increase in the risk of bleeding, especially intracranial and gastrointestinal bleeding. The availability of drugs such as clopidogrel, which inhibits platelet activity through the P2Y12 receptor pathway, has called into question this paradigm, also in consideration of the fact that the scientific evidence that supports the use of ASA in secondary prevention is based on dated studies with some limitations. Over the last few years, randomized trials have demonstrated how clopidogrel has an efficacy profile comparable to that of ASA and a safety profile that is sometimes even better. In light of the new evidence, it is therefore legitimate to ask whether in this clinical scenario, ASA should still be considered the drug of choice or whether clopidogrel could represent the preferable alternative.

Intracoronary imaging to guide percutaneous coronary intervention: from evidence to guidelines.

Despite notable advances in devices and techniques, percutaneous coronary intervention (PCI) is still affected by a substantial number of complications and failure rates. Over the years, the use of intracoronary imaging (ICI) has dramatically improved the understanding of mechanical and technical factors related to successful and failed PCI, becoming a mainstay in complex trans-catheter interventions. However, ICI modalities are invasive, time-consuming, and costly, and a net clinical benefit needs to be shown in order to recommend their routine use in clinical practice. In the past, the lack of evidence from randomized trials has been reflected in the scepticism shown by international guidelines. The recent publication of large randomized clinical trials conducted worldwide has provided new evidence regarding the clinical usefulness of ICI guidance in PCI. The consistent reduction of adverse events achieved in these trials, also demonstrated in an updated meta-analysis, suggested that the use of ICI in PCI is compelling to achieve optimal technical results and better outcomes, especially in complex high-risk interventions. Also considering the burden of information provided by ICI on coronary artery disease, looking from the inside seems today an opportunity that modern cardiology cannot ignore anymore.

Automatic assessment of atherosclerotic plaque features by intracoronary imaging: a scoping review.

Background: The diagnostic performance and clinical validity of automatic intracoronary imaging (ICI) tools for atherosclerotic plaque assessment have not been systematically investigated so far. Methods: We performed a scoping review including studies on automatic tools for automatic plaque components assessment by means of optical coherence tomography (OCT) or intravascular imaging (IVUS). We summarized study characteristics and reported the specifics and diagnostic performance of developed tools. Results: Overall, 42 OCT and 26 IVUS studies fulfilling the eligibility criteria were found, with the majority published in the last 5 years (86% of the OCT and 73% of the IVUS studies). A convolutional neural network deep-learning method was applied in 71% of OCT- and 34% of IVUS-studies. Calcium was the most frequent plaque feature analyzed (26/42 of OCT and 12/26 of IVUS studies), and both modalities showed high discriminatory performance in testing sets [range of area under the curve (AUC): 0.91-0.99 for OCT and 0.89-0.98 for IVUS]. Lipid component was investigated only in OCT studies (n = 26, AUC: 0.82-0.86). Fibrous cap thickness or thin-cap fibroatheroma were mainly investigated in OCT studies (n = 8, AUC: 0.82-0.94). Plaque burden was mainly assessed in IVUS studies (n = 15, testing set AUC reported in one study: 0.70). Conclusion: A limited number of automatic machine learning-derived tools for ICI analysis is currently available. The majority have been developed for calcium detection for either OCT or IVUS images. The reporting of the development and validation process of automated intracoronary imaging analyses is heterogeneous and lacks critical information. Systematic Review Registration: Open Science Framework (OSF), https://osf.io/nps2b/.Graphical AbstractCentral Illustration.

Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78-0.94) and ischemic stroke (HR 0.68, 95%CI 0.55-0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38-2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43-103) and the NNH to cause major bleeding was 107 (77-193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

Effects of Lipid Lowering Therapies on Vulnerable Plaque Features: An Updated Narrative Review of the Literature.

The clinical evidence on the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD) is unequivocally established. However, the effects of these therapies on plaque composition and stability are less clear. The use of intracoronary imaging (ICI) technologies has emerged as a complement to conventional angiography to further characterize plaque morphology and detect high-risk plaque features related to cardiovascular events. Along with clinical outcomes studies, parallel imaging trials employing serial evaluations with intravascular ultrasound (IVUS) have shown that pharmacological treatment has the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. Subsequently, the introduction of high-intensity lipid lowering therapy led to much lower levels of low-density lipoprotein cholesterol (LDL-C) levels than achieved in the past, resulting in greater clinical benefit. However, the degree of atheroma regression showed in concomitant imaging trials appeared more modest as compared to the magnitude of clinical benefit accrued from high-intensity statin therapy. Recently, new randomized trials have investigated the additional effects of achieving very low levels of LDL-C on high-risk plaque features-such as fibrous cap thickness and large lipid accumulation-beyond its size. This paper provides an overview of the currently available evidence of the effects of moderate to high-intensity lipid lowering therapy on high-risk plaque features as assessed by different ICI modalities, reviews data supporting the use of these trials, and analyse the future perspectives in this field.

Prediction of new onset atrial fibrillation in patients with acute coronary syndrome undergoing percutaneous coronary intervention using the C2HEST and mC2HEST scores: A report from the multicenter REALE-ACS registry.

BACKGROUND: New onset atrial fibrillation (NOAF) is associated with worse clinical outcomes after acute coronary syndrome (ACS). Identification of ACS patients at risk of NOAF remains challenging. To test the value of the simple C2HEST score for predicting NOAF in patients with ACS. METHODS: We studied patients from the prospective ongoing multicenter REALE-ACS registry of patients with ACS. NOAF was the primary endpoint of the study. The C2HEST score was calculated as coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age ≥ 75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). We also tested the mC2HEST score. RESULTS: We enrolled 555 patients (mean age 65.6 ± 13.3 years; 22.9% women), of which 45 (8.1%) developed NOAF. Patients with NOAF were older (p < 0.001) and had more prevalent hypertension (p = 0.012), chronic obstructive pulmonary disease (p < 0.001) and hyperthyroidism (p = 0.018). Patients with NOAF were more frequently admitted with STEMI (p < 0.001), cardiogenic shock (p = 0.008), Killip class ≥2 (p < 0.001) and had higher mean GRACE score (p < 0.001). Patients with NOAF had a higher C2HEST score compared with those without (4.2 ± 1.7 vs 3.0 ± 1.5, p < 0.001). A C2HEST score > 3 was associated with NOAF occurrence (odds ratio 4.33, 95% confidence interval 2.19-8.59, p < 0.001). ROC curve analysis showed good accuracy of the C2HEST score (AUC 0.71, 95%CI 0.67-0.74) and mC2HEST score (AUC 0.69, 95%CI 065-0.73) in predicting NOAF. CONCLUSIONS: The simple C2HEST score may be a useful tool to identify patients at higher risk of developing NOAF after presentation with ACS.

Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry.

AIMS: The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI). METHODS AND RESULTS: OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 µm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03-1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97-5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16-1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81-3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05-1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1-3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24-5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44-9.72; P < 0.001). CONCLUSIONS: A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study.

PURPOSE: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. METHODS: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. RESULTS: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. CONCLUSION: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

Relationship between non-invasively detected liver fibrosis and in-hospital outcomes in patients with acute coronary syndrome undergoing PCI.

BACKGROUND: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) still experience a high rate of in-hospital complications. Liver fibrosis (LF) is a risk factor for mortality in the general population. We investigated whether the presence of LF detected by the validated fibrosis 4 (FIB-4) score may indicate ACS patients at higher risk of poor outcome. METHODS: In the prospective ongoing REAl-world observationaL rEgistry of Acute Coronary Syndrome (REALE-ACS), LF was defined by a FIB-4 score > 3.25. We repeated the analysis using an APRI score > 0.7. The primary endpoint was in-hospital adverse events (AEs) including a composite of in-hospital cardiogenic shock, PEA/asystole, acute pulmonary edema and death. RESULTS: A total of 469 consecutive ACS consecutive patients were enrolled. Overall, 21.1% of patients had a FIB-4 score > 3.25. Patients with LF were older, less frequently on P2Y12 inhibitors (p = 0.021) and admitted with higher serum levels of white blood cells (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001), C-reactive protein (p = 0.013), hs-TnT (p < 0.001), creatine-kinase MB (p < 0.001), D-Dimer levels (p < 0.001). STEMI presentation and higher Killip class/GRACE score were more common in the LF group (p < 0.001). 71 patients experienced 110 AEs. At the multivariate analysis including clinical and laboratory risk factors, FIB-4 > 3.25 (OR 3.1, 95%CI 1.4-6.9), admission left ventricular ejection fraction% below median (OR 9.2, 95%CI 3.9-21.7) and Killip class ≥ II (OR 6.3, 95%CI 2.2-18.4) were the strongest independent predictors of in-hospital AEs. Similar results were obtained using the APRI score. CONCLUSION: LF detected by FIB-4 score > 3.25 was associated with more severe ACS presentation and worse in-hospital AEs irrespective of clinical and laboratory variables.

[From regression to stabilization: new insights into the evolution of coronary atherosclerotic plaque]. / Dalla regressione alla stabilizzazione: l'evoluzione della placca aterosclerotica coronarica secondo le nuove evidenze.

Coronary artery atherosclerosis is a constantly evolving disease. Over the years, new drug therapies have been shown to reduce adverse cardiovascular events and improve the survival of patients with coronary artery disease. New intracoronary imaging modalities, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have been introduced to detect the anatomic changes which follow an effective lipid-lowering therapy in human coronary plaques. Particularly, the use of optical coherence tomography made it possible to evaluate plaque composition and showed how an intensive lipid-lowering therapy can stabilize atherosclerosis by improving vulnerable plaque features. Future non-invasive applications are required for large-scale use of these findings.

The risk of acute coronary events in microvascular disease.

The microvascular disease represents a widespread clinical entity in the general population, especially among women. The dysfunction of the microcirculation is often responsible for myocardial ischaemia and angina in the absence of significant stenosis of the epicardial district, while in other cases it can represent a contributing cause of angina even in the presence of coronary artery disease, cardiomyopathies or heart failure. The cardiovascular risk factors of people with microvascular disease are similar to those who develop epicardial atherosclerotic disease. However, the prognostic significance of microvascular disease remains a matter of debate. An element to be clarified, in fact, is whether subjects with dysfunction of the microcirculation and coronary tree without significant stenoses present an increased risk of myocardial infarction and sudden death. In recent years, several studies seem to confirm an association between microvascular disease and progression of coronary epicardial atherosclerosis. The prognosis of microvascular disease would therefore not be benign as was previously believed, but associated with an increased risk of cardiovascular events including revascularization, heart attack, and cardiac death.

The Role of the Association Between Serum C-Reactive Protein Levels and Coronary Plaque Macrophage Accumulation in Predicting Clinical Events - Results from the CLIMA Registry.

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2-4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5-5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events.