Sodium-glucose cotransporter-2 inhibitors in heart failure patients across the range of body mass index: a systematic review and meta-analysis of randomized controlled trials.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with heart failure, with or without diabetes. We sought to assess whether there is an interaction of these effects with body mass index (BMI). A systematic review of the MEDLINE and Scopus databases (last search: November 15th, 2022) was performed according to the PRISMA statement. Studies eligible for this review were randomized control trials (RCTs) with patients with chronic heart failure with either preserved or reduced ejection fraction randomly assigned to SGLT2 inhibitors or placebo. Data were extracted independently by two reviewers. BMI was classified according to the WHO classification into under/normal weight (BMI: < 25 kg/m2), overweight (BMI: 25-29.9 kg/m2), obesity class I (BMI: 30-34.9 kg/m2), and obesity classes II/III (BMI: ≥ 35 kg/m2). All analyses were performed using RevMan 5.4. Among 1461 studies identified in the literature search, 3 were eligible and included in the meta-analysis. Among 14,737 patients (32.2% were women), 7,367 were randomized to an SGLT2 inhibitor (dapagliflozin or empagliflozin) and 7,370 to placebo. There were significantly fewer hospitalizations for HF (OR: 0.70, 95%CI: 0.64-0.76), cardiovascular deaths (OR:0.86, 95%CI: 0.77-0.97) and all-cause deaths (OR:0.90, 95%CI: 0.82-0.98) in the SGLT2 inhibitors group compared to the placebo group, without any interaction with BMI group (test for subgroup differences: x2 = 1.79, p = 0.62; x2 = 0.27, p = 0.97; x2 = 0.39, p = 0.94, respectively). There is no interaction between the efficacy of SGLT2 inhibitors and BMI in patients with HF with either preserved or reduced ejection fraction. SGLT2 inhibitors are associated with improved outcomes regardless of the BMI.Trial registration: PROSPERO ID: CRD42022383643.

ST-Segment Elevation Myocardial Infarction (STEMI) Management in the Era of COVID-19: A Systematic and Critical Review of Published Guidance Reports.

Background: Coronavirus disease 2019 (COVID-19) had a major impact on healthcare systems worldwide. During the early phase of the pandemic many elective procedures were postponed. At the same time, the safe and effective management of medical emergencies such as ST-segment elevation myocardial infarction (STEMI) has been a challenge. Methods: A systematic literature search was conducted aiming to identify published guidance reports by national or international societies regarding the management of patients suffering STEMI in the era of COVID-19. Results: Among 1681 articles initially retrieved, six fulfilled the inclusion criteria and were included in the systematic review. Two reports were international consensus documents, while four reports were national guidance statements from Asian countries (Taiwan, India, Iran, and China). Most documents were drafted during the early phase of the pandemic. According to the international consensus documents, percutaneous coronary intervention (PCI) should be regarded as the reperfusion method of choice. On the other hand, in three out of four national consensus statements (Taiwan, Iran and China) fibrinolysis was considered as the reperfusion method of choice for STEMI in suspected/confirmed patients with COVID-19, unless contraindicated or in the presence of high cardiovascular risk clinical features. Authors of all documents underlined the need for early COVID-19 testing in patients with STEMI to better determine the next therapeutical steps. Conclusions: National and international consensus statements for STEMI management in the era of COVID-19 have been published mainly during the early peak phase of the pandemic. Authors recognise that these recommendations are mainly based on expert opinions and observational data. As global immunization rates increase and methods for rapid COVID-19 detection are widely available, the implementation of traditional evidence-based practices used before the pandemic is becoming more feasible.

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials.

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.

Serum and Pleural Soluble Cell Adhesion Molecules in Mesothelioma Patients: A Retrospective Cohort Study.

Mesothelioma, a malignant neoplasm of mesothelial cells, has overall poor prognosis. Cell adhesion molecules (CAMs) are proteins that contribute to the immune response. In this study the clinical utility and prognostic significance of serum and pleural fluid soluble CAM (sCAM) levels were assessed in patients with mesothelioma. Mesothelioma patients were retrospectively recruited (2016-2020). Clinical characteristics, serum and pleural sCAM levels (sE-cadherin, sE-selectin, intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1)) and histopathological characteristics were gathered. A total of 51 healthy controls were also recruited for a secondary cross-sectional analysis. 92 mesothelioma patients were analyzed (mean age 64.5 years, 87% males, performance status 0-2). Patients with increased pleural sE-cadherin had higher risk for disease progression (adjusted HR 1.11 (1.02, 1.20), p = 0.013). Serum and pleural sE-selectin were decreased in patients with high-grade mesothelioma. Patients with increased serum or pleural sE-selectin levels had lower risk for death (adjusted HR 0.88 (0.81, 0.96), p = 0.003; 0.90 (0.82, 0.99), p = 0.039, respectively). Serum sE-cadherin, sE-selectin and sICAM-1 levels were significantly increased in mesothelioma patients compared to healthy controls. Further studies are needed to indicate the clinical utility of serum and pleural sCAMs in mesothelioma patients.

Clopidogrel Monotherapy versus Aspirin Monotherapy in Patients with Established Cardiovascular Disease: Systematic Review and Meta-Analysis.

BACKGROUND: There is no clear consensus on whether aspirin offers better outcomes in terms of secondary cardiovascular disease prevention compared with clopidogrel. OBJECTIVE: The aim of the study was to compare the safety and efficacy of clopidogrel versus aspirin in patients with established cardiovascular disease. METHODS: A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases (last search date: August 28, 2021) was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized control trials (RCTs) of clopidogrel versus aspirin as monotherapy in patients with established cardiovascular disease. Random-effects meta-analyses were performed. RESULTS: Five RCTs incorporating 26,855 patients (clopidogrel: 13,426; aspirin: 13,429) were included. No statistically significant difference was observed between clopidogrel and aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% confidence interval, CI: 0.91-1.13]; p = 0.83), ischemic stroke (OR: 0.87 [95% CI: 0.71-1.06]; p = 0.16), and major bleeding rates (OR: 0.77 [95% CI: 0.56-1.06]; p = 0.11). Patients receiving clopidogrel had borderline lower risk for major adverse cardiovascular events (MACE) (OR: 0.84 [95% CI: 0.71-1.00]; p = 0.05) and lower risk for nonfatal myocardial infarction (OR: 0.83 [95% CI: 0.71-0.97]; p = 0.02, relative risk reduction = 16.9%, absolute risk reduction = 0.5%, number needed to treat = 217 for a mean period of 20 months) compared with patients receiving aspirin. CONCLUSION: In patients with established cardiovascular disease, clopidogrel was associated with a 17% relative-risk reduction for nonfatal MI, borderline decreased risk for MACE, and similar risk for all-cause mortality, stroke, and major bleeding compared with aspirin. PROTOCOL REGISTRATION: PROSPERO CRD42021283866.

Influenza Vaccination in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

The safety and efficacy of influenza vaccination is not well-studied in cancer patients receiving immune checkpoint inhibitors (ICIs). A systematic review and meta-analysis was performed aiming to summarize available data regarding influenza vaccination in ICI-treated cancer patients. Peer-reviewed studies or nonpeer-reviewed conference abstracts including ICI-treated cancer patients who received at least 1 dose of influenza vaccine were deemed eligible. A systematic search in PubMed/EMBASE was performed until October 26, 2021. Endpoints of interest included mortality as the primary outcome and secondary safety outcomes such as the incidence of immune-related adverse events (irAEs). Twenty-five studies were included in the systematic review, among which 9 were included in the meta-analysis. Meta-analysis of 3 studies (n=589, weighted age 64 y, men 61%, influenza vaccinated 32%) showed pooled odds ratio for death in influenza vaccinated versus nonvaccinated patients at 1.25 [(95% confidence intervals (CI): 0.81-1.92), P=non significant (NS)]. Meta-analysis of 6 studies studies (n=1285, weighted age 60 y, men 59%, influenza vaccinated 48%) showed pooled odds ratio for any irAEs in influenza vaccinated versus nonvaccinated patients at 0.82 [95% CI: 0.63-1.08, P=NS]. Similar results were observed in sensitivity analyses for serious irAEs, as well as when only peer-reviewed studies were included. Influenza vaccination appears to be a safe and reasonable intervention for cancer patients receiving ICIs. Most data are derived from retrospective observational studies. Randomized studies are needed to provide high-quality evidence.

Thromboprophylaxis in Patients with COVID-19: Systematic Review of National and International Clinical Guidance Reports.

BACKGROUND: Venous Thromboembolism (VTE) is common among patients with severe Coronavirus Disease 2019 (COVID-19). Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal thromboprophylaxis strategy has not yet been defined. OBJECTIVE: To identify published guidance reports by national and international societies regarding thromboprophylaxis strategies in COVID-19 patients in different settings (outpatients, hospitalized, post-discharge). METHODS: A systematic review of the literature (Pubmed/EMBASE) was conducted independently by two investigators. RESULTS: Among 1942 initially identified articles, 33 guidance documents were included: 20 published by national and 13 by international societies. These documents provide recommendations mainly for hospitalized (97% of reports) and post-discharge (75%) COVID-19 patients, and less so for outpatients (34%). Thrombotic and bleeding risk stratification prior to any treatment decision is the cornerstone of all suggested thromboprophylaxis strategies; 81% of the documents recommend thromboprophylaxis for all hospitalized patients with a prophylactic dosage of low molecular weight heparin irrespective of VTE risk. Intermediate or therapeutic dose intensity is recommended in high VTE risk patients by 56% and 28% of documents, respectively. Mechanical thromboprophylaxis is suggested in case of high bleeding risk or contraindication to pharmacological thromboprophylaxis (59% of documents). Extended pharmacological thromboprophylaxis is recommended for patients with high VTE risk after hospital discharge (63% of documents). For non-hospitalized outpatients, 28% of documents recommend pharmacological thromboprophylaxis for high VTE risk. CONCLUSION: The current guidance identifies thromboprophylaxis in COVID-19 patients, especially during hospitalization, as of major importance for the prevention of VTE. Recommendations are derived from limited evidence from observational studies.

Cardiac Injury in COVID-19: A Systematic Review of Relevant Meta-Analyses.

Background: Cardiac injury (CI) is not a rare condition among hospitalized patients with coronavirus disease 2019 (COVID-19). Its prognostic value has been extensively reported through the literature, mainly in the context of observational studies. An impressive number of relevant meta-analyses has been conducted. These meta-analyses present similar and consistent results; yet interesting methodological issues emerge. Methods: A systematic literature search was conducted aiming to identify all relevant meta-analyses on (i) the incidence, and (ii) the prognostic value of CI among hospitalized patients with COVID-19. Results: Among 118 articles initially retrieved, 73 fulfilled the inclusion criteria and were included in the systematic review. Various criteria were used for CI definition mainly based on elevated cardiac biomarkers levels. The most frequently used biomarker was troponin. 30 meta-analyses reported the pooled incidence of CI in hospitalized patients with COVID-19 that varies from 5% to 37%. 32 meta-analyses reported on the association of CI with COVID-19 infection severity, with only 6 of them failing to show a statistically significant association. Finally, 46 meta-analyses investigated the association of CI with mortality and showed that patients with COVID-19 with CI had increased risk for worse prognosis. Four meta-analyses reported pooled adjusted hazard ratios for death in patients with COVID-19 and CI vs those without CI ranging from 1.5 to 3. Conclusions: The impact of CI on the prognosis of hospitalized patients with COVID-19 has gained great interest during the pandemic. Methodological issues such as the inclusion of not peer-reviewed studies, the inclusion of potentially overlapping populations or the inclusion of studies with unadjusted analyses for confounders should be taken into consideration. Despite these limitations, the adverse prognosis of patients with COVID-19 and CI has been consistently demonstrated.

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19.

The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis.

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis.

BACKGROUND AND AIMS: Statin therapy is administered to patients with high cardiovascular risk. These patients are also at risk for severe course of coronavirus disease 2019 (COVID-19). Statins exhibit not only cardioprotective but also immunomodulatory and anti-inflammatory effects. This study performed a systematic review of published evidence regarding statin treatment and COVID-19 related mortality. METHODS: A systematic PubMed/Embase search was performed from February 10, 2020 until March 05, 2021 for studies in COVID-19 patients that reported adjusted hazard or odds ratio for death in statin users versus non-users. RESULTS: 22 studies fulfilled the inclusion criteria and were included in the systematic review. Meta-analysis of 10 studies (n = 41,807, weighted age 56 ± 8 years, men 51%, hypertension 34%, diabetes 21%, statin users 14%) that reported adjusted hazard ratios for mortality in statin users versus non-users showed pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). Meta-analysis of 6 studies that reported continuation of statin therapy during hospitalization (58-100% of patients) revealed a pooled hazard ratio of 0.54 (95% CI 0.47, 0.62). Meta-analysis of 12 studies (n = 72,881, weighted age 65 ± 2 years, men 54%, hypertension 66%, diabetes 43%, statin users 30%) that reported adjusted odds ratios for mortality showed pooled estimate at 0.65 (95% CI 0.55, 0.78). Multivariable meta-regression analysis did not reveal any significant association of hazard or odds ratios with anthropometric characteristics or comorbidities. CONCLUSIONS: This meta-analysis of retrospective observational studies showed that statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients.