Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by severe acute respiratory syndrome coronavirus‐2, which has posed a significant threat to global health. Although the infection is frequently asymptomatic or associated with mild symptoms, in a small proportion of patients it can produce an intense inflammatory and prothrombotic state that can lead to acute respiratory distress syndrome, multiple organ failure, and death. Angiotensin‐converting enzyme 2, highly expressed in the respiratory system, has been identified as a functional receptor for severe acute respiratory syndrome coronavirus‐2. Notably, angiotensin‐converting enzyme 2 is also expressed in the cardiovascular system, and there are multiple cardiovascular implications of COVID‐19. Cardiovascular risk factors and cardiovascular disease have been associated with severe manifestations and poor prognosis in patients with COVID‐19. More important, patients with COVID‐19 may have thrombotic and coagulation abnormalities, promoting a hypercoagulable state and resulting in an increased rate of thrombotic and thromboembolic events. This review will describe the pathophysiological characteristics of the cardiovascular involvement following infection by severe acute respiratory syndrome coronavirus‐2, with a focus on thrombotic and thromboembolic manifestations and implications for antithrombotic management.

The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits particularly in patients with diabetes mellitus (DM), but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined. Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 RCTs and diverse populations using advanced meta-analytic methods. Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in pre-specified subgroups based on the GLP-1 RA used. Pre-specified subgroups according to DM, kidney function, obesity or heart failure (HF) were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events (SAEs). GRADE and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively. A total of 21 trials encompassing 99,592 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high certainty, evidence that GLP-1 RAs reduced all-cause death (IRR 0.88, 95% CI 0.84-0.92, NNT=121), CV death (IRR 0.87, 95% CI 0.81-0.92, NNT=170) and MACE (IRR 0.87, 95% CI 0.83-0.91, NNT=66), compared with controls. GLP-1 RAs reduced SAE (-9%), myocardial infarction (-15%), acute kidney failure (-9%), HF (-15%), and infections (-10%), but increased gastrointestinal (GI; +63%) and gallbladder (+26%) disorders. There were no differences in stroke, pancreatitis or neoplasm between groups. Results were mostly consistent across subgroups. Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles. GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased GI and gallbladder risks. Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals.

Background: The clinical impact of different prophylactic anticoagulation regimens among hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. We pooled evidence from available randomized controlled trials (RCTs) to provide insights on this topic. Methods and results: We searched for RCTs comparing treatment with an escalated-dose (intermediate-dose or therapeutic-dose) vs. a standard-dose prophylactic anticoagulation regimen in critically and non-critically ill COVID-19 patients requiring hospitalization and without a formal indication for anticoagulation. The primary efficacy endpoint was all-cause death, and the primary safety endpoint was major bleeding. Seven RCTs were identified, including 5154 patients followed on an average of 33 days. Compared to standard-dose prophylactic anticoagulation, escalated-dose prophylactic anticoagulation was not associated with a reduction of all-cause death [17.8% vs. 18.6%; risk ratio (RR) 0.96, 95% confidence interval (CI) 0.78–1.18] but was associated with an increase in major bleeding (2.4% vs. 1.4%; RR 1.73, 95%CI 1.15–2.60). Compared to prophylactic anticoagulation used at a standard dose, an escalated dose was associated with lower rates of venous thromboembolism (2.5% vs. 4.7%; RR 0.55, 95%CI 0.41–0.74) without a significant effect on myocardial infarction (RR 0.80, 95%CI 0.47–1.36), stroke (RR 0.94, 95%CI 0.43–2.09), or systemic arterial embolism (RR 1.20, 95%CI 0.29–4.95). There were no significant interactions in the subgroup analysis for critically and non-critically ill patients. Conclusions: Our findings provide comprehensive and high-quality evidence for the use of standard-dose prophylactic anticoagulation over an escalated-dose regimen as routine standard of care for hospitalized patients with COVID-19 who do not have an indication for therapeutic anticoagulation, irrespective of disease severity. Study registration: This study is registered in PROSPERO (CRD42021257203).