Management of dyslipidemias with fibrates, alone and in combination with statins: role of delayed-release fenofibric acid

Cardiovascular disease (CVD) represents the leading cause of mortality worldwide. Lifestyle modifications, along with low-density lipoprotein cholesterol (LDL-C) reduction, remain the highest priorities in CVD risk management. Among lipid-lowering agents, statins are most effective in LDL-C reduction and have demonstrated incremental benefits in CVD risk reduction. However, in light of the residual CVD risk, even after LDL-C targets are achieved, there is an unmet clinical need for additional measures. Fibrates are well known for their beneficial effects in triglycerides, high-density lipoprotein cholesterol (HDL-C), and LDL-C subspecies modulation. Fenofibrate is the most commonly used fibric acid derivative, exerts beneficial effects in several lipid and nonlipid parameters, and is considered the most suitable fibrate to combine with a statin. However, in clinical practice this combination raises concerns about safety. ABT-335 (fenofibric acid, Trilipix®) is the newest formulation designed to overcome the drawbacks of older fibrates, particularly in terms of pharmacokinetic properties. It has been extensively evaluated both as monotherapy and in combination with atorvastatin, rosuvastatin, and simvastatin in a large number of patients with mixed dyslipidemia for up to 2 years and appears to be a safe and effective option in the management of dyslipidemia

Modelling the Role of Dietary Habits and Eating Behaviours on the Development of Acute Coronary Syndrome or Stroke: Aims, Design, and Validation Properties of a Case-Control Study

In this paper the methodology and procedures of a case-control study that will be developed for assessing the role of dietary habits and eating behaviours on the development of acute coronary syndrome and stroke is presented. Based on statistical power calculations, 1000 participants will be enrolled; of them, 250 will be consecutive patients with a first acute coronary event, 250 consecutive patients with a first ischaemic stroke, and 500 population-based healthy subjects (controls), age and sex matched to the cases. Socio-demographic, clinical, dietary, psychological, and other lifestyle characteristics will be measured. Dietary habits and eating behaviours will be evaluated with a special questionnaire that has been developed for the study

Acid-Base and Electrolyte Abnormalities in Patients With Acute Leukemia

Disturbances of acid-base balance and electrolyte abnormalities are commonly seen in patients with acute leukemia. Our study aimed at illuminating the probable pathogenetic mechanisms responsible for these disturbances in patients with acute leukemia admitted to our hospital. We studied 66 patients (24 men and 44 women) aged between 17 and 87 years old on their admission and prior to any therapeutic intervention. Patients with diabetes mellitus, acute or chronic renal failure, hepatic failure, patients receiving drugs that influence acid-base status and electrolyte parameters during the last month, such as corticosteroids, cisplatin, diuretics, antacids, aminoglycosides, amphotericin, penicillin, and K + , PO 4 3− , or Mg 2+ supplements were excluded. Forty-one patients had at least one acid-base or electrolyte disturbance. There were no significant differences in the incidence of acid-base balance and electrolyte abnormalities between patients with acute myeloid leukemia (AML) and patients with acute lymphoblastic leukemia (ALL). The most frequent electrolyte abnormality was hypokalemia, observed in 41 patients (63%), namely in 34 patients with AML, and 7 with ALL; the main underlying pathophysiologic mechanism was inappropriate kaliuresis. Furthermore, hypokalemic patients more frequently experienced concurrent electrolyte disturbances (i.e., hyponatremia, hypocalcemia, hypophosphatemia, and hypomagnesemia), as well as various acid-base abnormalities compared to normokalemic patients. Hypokalemia in patients with acute leukemia may serve as an indicator of multiple concurrent, interrelated electrolyte disturbances, especially in patients with AML. Am

Association between sodium-glucose cotransporter-2 inhibitors and incident atrial fibrillation/atrial flutter in heart failure patients with reduced ejection fraction: a meta-analysis of randomized controlled trials

Atrial fibrillation (AF) and atrial flutter (AFL) are associated with adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We investigated the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the incidence of AF and/or AFL in HFrEF patients. PubMed and linicalTrials.gov were systematically searched until March 2022 for randomized controlled trials (RCTs) that enrolled patients with HFrEF. A total of six RCTs with 9467 patients were included (N=4731 in the SGLT2i arms; N=4736 in the placebo arms). Compared to placebo, SGLT2i treatment was associated with a significant reduction in the risk of AF [relative risk (RR) 0.62, 95% confidence interval CI 0.44–0.86; P=0.005] and AF/AFL (RR 0.64, 95% CI 0.47–0.87; P=0.004). Subgroup analysis showed that empagliflozin use resulted in a significant reduction in the risk of AF (RR 0.55, 95% CI 0.34–0.89; P=0.01) and AF/AFL (RR 0.50, 95% CI 0.32–0.77; P=0.002). By contrast, dapagliflozin use was not associated with a significant reduction in the risk of AF (RR 0.69, 95% CI 0.43–1.11; P=0.12) or AF/AFL (RR 0.82, 95% CI 0.53–1.27; P=0.38). Additionally, a “shorter” duration (<1.5 years) of treatment with SGLT2i remained associated with a reduction in the risk of AF (<1.5 years; RR 0.58, 95% CI 0.36–0.91; P=0.02) and AF/AFL (<1.5 years; RR 0.52, 95% CI 0.34–0.80; P=0.003). In conclusion, SGLT2i therapy was associated with a signifcant reduction in the risk of AF and AF/AFL in patients with HFrEF. These results reinforce the value of using SGLT2i in this setting

Atrial High-Rate Episode Duration Thresholds and Thromboembolic Risk: A Systematic Review and Meta-Analysis

BACKGROUND: Available evidence supports an association between atrial high‐rate episode (AHRE) burden and thromboembolic risk, but the necessary extent and duration of AHREs to increase the thromboembolic risk remain to be defined. The aim of this systematic review and meta‐analysis was to identify the thromboembolic risk associated with various AHRE thresholds. METHODS AND RESULTS: We searched PubMed and Scopus until January 9, 2020, for literature reporting AHRE duration and thromboembolic risk in patients with implantable electronic devices. The outcome assessed was stroke or systemic embolism. Risk estimates were reported as hazard ratio (HR) or relative risk alongside 95% CIs. We used the Paule‐Mandel estimator, and heterogeneity was calculated with I(2) index. Among 27 studies including 61 919 patients, 23 studies reported rates according to the duration of the longest AHRE and 4 studies reported rates according to the cumulative day‐level AHRE duration. In patients with cardiac implantable devices, AHREs lasting ≥30 seconds significantly increased the risk of stroke or systemic embolism (HR, 4.41; 95% CI, 2.32–8.39; I(2), 5.5%), which remained consistent for the thresholds of 5 minutes and 6 and 24 hours. Patients with previous stroke or transient ischemic attack and AHREs lasting ≥2 minutes had a marginally increased risk of recurrent stroke or transient ischemic attack. The risk of stroke or systemic embolism was higher in patients with cumulative AHRE ≥24 hours compared with those of shorter duration or no AHRE (HR, 1.25; 95% CI, 1.04–1.52; I(2), 0%). CONCLUSIONS: This systematic review and meta‐analysis suggests that single AHRE episodes ≥30 seconds and cumulative AHRE duration ≥24 hours are associated with increased risk of stroke or systemic embolism

The association between Type D personality and the metabolic syndrome: a cross-sectional study in a University-based outpatient lipid clinic

<p>Abstract</p> <p>Background</p> <p>Type D personality has been associated in the past with increased cardiovascular mortality among patients with established coronary heart disease. Very few studies have investigated the association of type D personality with traditional cardiovascular risk factors. In this study, we assessed the association between type D personality and the metabolic syndrome.</p> <p>Findings</p> <p>New consecutive patients referred to an outpatient lipid clinic for evaluation of possible metabolic syndrome were eligible for inclusion in the study. The metabolic syndrome was defined according to the International Diabetes Federation (IDF) diagnostic criteria. Type D personality was assessed with the DS-14 scale. Multivariate regression techniques were used to investigate the association between personality and metabolic syndromes adjusting for a number of medical and psychiatric confounders. Three hundred and fifty-nine persons were screened of whom 206 met the diagnostic criteria for the metabolic syndrome ("cases") and 153 did not ("control group"). The prevalence of type D personality was significantly higher in the cases as compared to the control group (44% versus 15% respectively, p < 0.001). In multivariate logistic regression analysis the presence of Type D personality was significantly associated with metabolic syndrome independently of other clinical factors, anxiety and depressive symptoms (odds ratio 3.47; 95% Confidence Interval: 1.90 - 6.33).</p> <p>Conclusions</p> <p>Type D personality was independently associated with the metabolic syndrome in this cross-sectional study. The potential implications of this finding, especially from a clinical or preventive perspective, should be examined in future research.</p

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment

BackgroundInfections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke. MethodsWe conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR 1 harm). This trial is registered (ISRCTN82217627). FindingsFrom April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81–1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77–1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96–1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events. InterpretationWe observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke. FundingThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No: 634809

Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at and ) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.Peer reviewe