The identification of ketotifen as a novel cardioprotective agent in patients undergoing anthracyclines chemotherapy

Objective: The present study aimed to investigate the possible cardioprotective effects of ketotifen and to assess its activity as an iron-chelating agent in patients receiving anthracyclines for the treatment of breast cancer. Patients & Methods: This was a randomized, prospective, controlled clinical trial. One hundred eleven eligible patients with breast cancer (age range, 30-60 years) were scheduled to receive anthracyclines chemotherapy. The patients were divided into two groups: Patients (n = 56) assigned to the ketotifen group received ketotifen 1 mg three times daily for six consecutive cycles of treatment, and patients assigned to the control group (n = 55) without ketotifen treatment. The echocardiogram for each patient was recorded two times at baseline and the end of the study. As well, blood samples were collected from all patients. Results: The findings showed a statistically significant reduction in the mean serum levels of common cardiotoxicity accompanied biomarkers in the ketotifen group compared with the control group (P ≤ 0.05). The mean serum levels of total iron-binding capacity were significantly elevated in the ketotifen group (P ≤ 0.001). There was a direct correlation between the mean serum levels of iron and that of lactate dehydrogenase (LDH) (r = + 0.79). On the other hand, there were indirect correlations between mean serum levels of LDH and both the percentage of ejection fraction and the total iron-binding capacity (r = - 0.69 and -0.697, respectively). Conclusion: Oral administration of ketotifen appears to be efficient and safe as a novel cardioprotective agent for the prevention of anthracyclines induced cardiotoxicity. Additionally, ketotifen suggested a beneficial effect in iron overload inducing diseases such as COVID-19.