Can glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors help in mitigating the risk of atrial fibrillation in patients with diabetes?

The role of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in mitigating the risk of atrial fibrillation (AF) remains unknown. We interrogated the Food and Drug Administration\u27s Adverse Event Reporting System (FAERS) database to study the association between AF-related adverse events and the use of GLP-1 RA and DPP-4i. A signal of disproportionate reporting of AF was detected with the DPP-4i group compared with all the other drugs in the FAERS database [ROR, 2.56; 95% confidence interval (CI), 2.10-3.12], whereas there was no disproportionality signal detected with the GLP-1 RA group (ROR, 0.90; 95% CI, 0.78-1.03) although liraglutide showed a significant disproportionality signal (ROR, 2.51; 95% CI, 2.00-3.15). Our analysis supports the existing body of literature demonstrating the cardiac safety of GLP-1 RA but raises concerns about the apparent increase in the risk of AF associated with DPP-4i. Further clinical and translational studies are needed to validate these findings

Cardiovascular complications associated with novel agents in the chronic lymphocytic leukemia armamentarium: A pharmacovigilance analysis

INTRODUCTION: Over the last few years, improved outcomes in patients with chronic lymphocytic leukemia (CLL) have been credited to the introduction of novel agents for its treatment. However, the overall cardiovascular safety profile of these agents has not been studied adequately. METHODS: We searched the Food and Drug Administration Adverse Event Reporting System (FAERS) database for adverse events reported for several of these novel agents: ibrutinib, acalabrutinib, venetoclax, and idelalisib. RESULTS: A total of 6074 cardiac adverse events were identified; ibrutinib (4832/36581; 13.2%) was found to have the highest risk of cardiac adverse events. The frequency of atrial fibrillation was highest (41.5%) in the ibrutinib group, while the idelalisib and acalabrutinib groups had the highest reported frequencies of heart failure (25.1%) and myocardial infarction (13.6%), respectively. Hypertension was noted to be relatively higher in the acalabrutinib (25.6%) and venetoclax (11.8%) groups. Overall reported mortality associated with cardiac events was highest in the venetoclax (29.4%) and idelalisib (27.1%) groups. CONCLUSION: Novel agents in the CLL armamentarium have been associated with several cardiovascular adverse events. Further studies are needed to identify high-risk groups that would benefit from robust cardiovascular surveillance after initiation of treatment with these novel agents

Possible mechanisms responsible for acute coronary events in COVID-19

The novel coronavirus (SARS-CoV-2) is primarily a respiratory pathogen and its clinical manifestations are dominated by respiratory symptoms, the most severe of which is acute respiratory distress syndrome (ARDS). However, COVID-19 is increasingly recognized to cause an overwhelming inflammatory response and cytokine storm leading to end organ damage. End organ damage to heart is one of the most severe complications of COVID-19 that increases the risk of death. We proposed a two-fold mechanism responsible for causing acute coronary events in patients with COVID-19 infection: Cytokine storm leading to rapid onset formation of new coronary plaques along with destabilization of pre-existing plaques and direct myocardial injury secondary to acute systemic viral infection. A well-coordinated immune response is the first line innate immunity against a viral infection. However, an uncoordinated response and hypersecretion of cytokines and chemokines lead to immune related damage to the human body. Human Coronavirus (HCoV) infection causes infiltration of inflammatory cells that cause excessive production of cytokines, proteases, coagulation factors, oxygen radicals and vasoactive molecules causing endothelial damage, disruption of fibrous cap and initiation of formation of thrombus. Systemic viral infections also cause vasoconstriction leading to narrowing of vascular lumen and stimulation of platelet activation via shear stress. The resultant cytokine storm causes secretion of hypercoagulable tissue factor without consequential increase in counter-regulatory pathways such as AT-III, activated protein C and plasminogen activator type 1. Lastly, influx of CD4+ T-cells in cardiac vasculature results in an increased production of cytokines that stimulate smooth muscle cells to migrate into the intima and generate collagen and other fibrous products leading to advancement of fatty streaks to advanced atherosclerotic lesions. Direct myocardial damage and cytokine storm leading to destabilization of pre-existing plaques and accelerated formation of new plaques are the two instigating mechanisms for acute coronary syndromes in COVID-19