ABSTRACT
Newly approved cancer drugs called ICIs have shown remarkable success in improving patient survival rates, but they also have the potential for inflammatory and immune-related side effects, including those affecting the cardiovascular system. Research has been conducted to understand the development of these toxicities and identify risk factors. This review focuses on the characteristics of ICI-induced cardiotoxicity and discusses the reported risk factors. It is important for cardio-oncologists to understand the basic concepts of these drugs to better understand how cardiotoxicities occur. It might be hard to find reports, where all patients treated with ICIs had developed cardiac toxicity, because there could be other existing and variable factors that influence the likelihood or risk of developing cardiotoxicity during treatment. Various clinical parameters have been explored as potential risk factors, and further investigation is needed through large-scale studies.
Subject(s)
Cardiotoxicity , Immune Checkpoint Inhibitors , Humans , Cardiotoxicity/etiology , Heart , Risk FactorsABSTRACT
Objective: Recently, several researchers have reported the incidence of cardiac-related toxicities occurring with nivolumab (Opdivo) and pembrolizumab (Keytruda). There is still a need for balance between oncology treatment efficacy and reduction of cardiotoxicity burden in immune checkpoint inhibitor (ICI)-treated patients. Thus, the primary aim was to determine whether pembrolizumab or nivolumab would present with a greater risk for cardiotoxicity reports. Materials and methods: This meta-analysis was performed with respect to the MOOSE reporting guidelines. Studies were retrieved by searching PubMed, Embase, and Google Scholar; the search terms were Keytruda or Pembrolizumab, PD1 inhibitors, anti-PD1 drugs, Nivolumab or Opdivo, and cardiotoxicities or cardiac toxicity. The study was restricted to original articles investigating ICI-induced cardiac immune-related adverse events (irAEs). The targeted population was cancer patients treated with either pembrolizumab or nivolumab monotherapy, of which those with records of any cardiac events following the therapy were labeled as events. The measures used to achieve the comparison were descriptive proportions, probabilities, and meta-analysis pooled odds ratios (ORs). Results: Fifteen studies were included in this meta-analysis. Nivolumab accounted for 55.7% cardiotoxicity and pembrolizumab, for 27.31% (P = 0.027). The meta-analysis was based on the Mantel-Haenszel method, and the random-effect model yielded a pooled OR = 0.73 (95% CI [0.43-1.23] P = 0.24), with considerable heterogeneity (I2 = 99% P = 0). Hence, the difference in cardiotoxicity odds risk between pembrolizumab and nivolumab was not statistically significant. On subgroup analysis based on cardiotoxicity type, the "myocarditis" subgroup in which there was no statistical heterogeneity was associated with a significant cardiotoxicity risk increase with pembrolizumab (OR = 1.30 [1.07;1.59], P< 0.05; I2 = 0%, Ph = 0.4). Conclusion: To our knowledge, this is the first meta-analysis to compare the cardiotoxicity potentials of nivolumab and pembrolizumab. In contrast to previous reports, the overall findings here demonstrated that nivolumab-induced cardiotoxicity was more commonly reported in the literature than pembrolizumab; however, myocarditis seemed more likely to occur with pembrolizumab therapy.
ABSTRACT
BACKGROUND: An increased leukocyte count is a sign of inflammation and has been demonstrated to be a predisposing factor and complication of atrial fibrillation. Similarly, albumin, the major protein in the serum, is also considered an acute phase reactant protein that has osmotic and anti-inflammatory properties, and a low albumin level is a known factor associated with severity in many pathologies, including atrial fibrillation. The neutrophil percentage-to-albumin ratio (NPAR) and other emerging leukocyte counts/albumin ratios have been reliable systemic inflammation-based predictors of mortality and complications in various diseases, but they have not yet been used with atrial fibrillation. This study's aim was to explore whether the leukocyte to albumin ratio could also serve as a useful index in estimating atrial fibrillation severity, including the severity of atrial fibrillation secondary to stroke, to provide a new and more objective tool than the conventional and medical history-based CHA2DS2-VASc score. MATERIALS AND METHODS: Data were retrospectively collected from the Wuhan University Zhongnan Hospital database from January 1st to December 31st, 2021. The patients were classified into 2 groups: Group 1-low severity and Group 2- moderate to high severity, and diverse statistical analyses were conducted to evaluate the relationship between the leukocyte-to-albumin ratio and AF severity. RESULTS: Only 2329 test subjects met the inclusion criteria. We had 727 test subjects (381 males and 346 females) categorized into the low severity cohort and 1601 test subjects (932 males and 670 females) in the moderate to high severity group. The difference in mean age between the two groups was significant (95% CI [-2.682 to -0.154] p = 0.028), and the difference in the LAR mean rank between the two groups was significant (p = 0.00). The Chi-square test of association yielded the following results: the relationship between the LAR level and category of severity was statistically significant (p = 0.00), and the MantelâHaenszel statistic association odds ratio was OR = 0.657. 95% CI OR [0.549-0.787] p = 0.000. The association between sex and atrial fibrillation severity also reached statistical significance. However, sex and LAR were found to be independent factors in atrial fibrillation (Chi-square p value = 0.564). CONCLUSION: It has been demonstrated throughout this investigation that the leukocyte to albumin ratio could provide key clues in clinical practice and contribute to thromboembolism risk assessment in the setting of atrial fibrillation.
