Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied in the past and clear guidelines for management of these side effects are available in the literature. However, cardiotoxicity with novel agents such as ICIs has been fairly under-reported and/or underestimated and we are yet to formulate clear guidelines for management of these rare side effects. In the last few years, there has been an overall increase in the number of cases of cardiotoxicity related to ICIs. In this literature review, we describe the mechanism of action of the most widely used ICIs and their related cardiotoxicities. The increase in number of case reports about the potential of cardiotoxicities with these novel agents clearly indicates the need for a new insight into the field of cardio-immuno-oncology.
Objective: To investigate the association between using febuxostat and cardiovascular events. Methods: Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality. Results: A total of 15 randomized controlled trials (16,070 participants) were included. The mean AE SD age was 58.1AE11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI,-0.25% to 0.49%; I 2 ¼48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI,-0.28% to 0.68%; I 2 ¼60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI,-0.34% to 1.13%; I 2 ¼26%; low certainty evidence), myocardial infarction (RD,-0.06%; 95% CI,-0.29% to 0.17%; I 2 ¼0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI,-0.15% to 0.35%; I 2 ¼0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI,-0.63% to 3.78%; I 2 ¼58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease. Conclusion: This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.
Highlights
The risk of events is thought to be linear with the high-sensitivity troponin level.
The absolute troponin level might not be the sole determinant of risk, however.
Chest pain patients with stable low-level troponin elevation pose a challenge.
High-sensitivity troponin T ≤ 50 ng/l with a rise < 5 ng/l identify a low-risk cohort.
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