RESUMEN
Vascular endothelial growth factor receptor inhibitors (VEGFRi), namely axitinib, are commonly used chemotherapeutic agents in patients with cancer; however, this medication has a significant cardiovascular side effect profile, such as high-grade hypertension. We performed this updated meta-analysis of RCTs to compile cardiovascular adverse events, such as all-grade and high-grade (>3) hypertension, the risk for thrombosis (DVT and PE), and peripheral edema. A systematic search was performed on PubMed, Cochrane, and Embase from inception until October 2023 for studies using axitinib to treat various cancers. Trials with patients randomly allocated for VEGFRi drug therapy with axitinib and reported all-grade hypertension as an outcome were included. Statistical analysis was performed using Cochrane Review Manager to calculate pooled proportions of odds ratios (OR) with a 95 % confidence interval (CI) using the random-effects model, Mantel-Haenszel method. A total of 8 RCTs and 2502 patients were included in the review. Compared with the placebo group, the VEGFRi (Axitinib) therapy group was associated with a higher risk of all-grade and high-grade hypertension, hand-foot syndrome, and fatigue. Furthermore, there was no increased risk of thromboembolism (DVT/PE) or hypothyroidism. However, a lower risk of peripheral edema was noted between the two groups. Screening for patients with preexisting hypertension, identifying risk factors for cardiovascular diseases before the initiation of VEGFRi therapy, and careful monitoring of high-risk patients during VEGFRi therapy, as well as prompt treatment with antihypertensive drugs, will help mitigate the adverse effects. Further evaluation using prospective designs is required to study the clinical significance and develop mitigation strategies.
RESUMEN
BACKGROUND: Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population. METHODS: This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening). RESULTS: R-value measured by TEG was shorter during awakening hours than during the night and day hours (p < 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p < 0.05). CONCLUSION: Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.
