Long-Term and Transient Calcium Channel Blockers; A Systematic Review of Their Role in the Management of Cardiomyopathy in Transfusion-Dependent Thalassemia.

Abstract

Calcium channel blockers (CCBs) for long-term (L) and transient (T) calcium channels (LTCC and TTCC) on cardiomyocytes have been suggested to manage iron-induced cardiomyopathy in transfusion-dependent thalassemia patients. However, the results of clinical trials on the effectiveness of CCBs have been conflicting. Here, we systematically reviewed previous studies to investigate the potential factors that could act as therapeutic modifiers and explain these discrepancies. This systematic review was conducted employing the PRISMA guideline to retrieve clinical trials and animal studies investigating the efficacy of CCBs. Studies in the following databases were collected: Web of Science, PubMed, Scopus, Google Scholar, Clinical Trials, Iranian Registry for Clinical Trials, and Cochrane CENTRAL. Keywords included the trade and generic names of various CCBs, thalassemia, and cardiomyopathy. Our Primary search resulted in 297 studies, of which 21 (n = 7 trials and n = 14 animal studies) were further analyzed. The most important parameters that could potentially influence the clinical effectiveness of CCBs in managing iron-induced cardiomyopathy included baseline cardiac iron content, diversity of iron entry routes (LTCCs, TTCCs, DMT-1, etc.), type of CCBs used, iron-induced irreversible functional/structural cardiac changes, iron-Ca²⁺ joint metabolic dysregulation, deregulated expression of LTCCs and TTCCs, interaction of CCBs with iron chelators, disease-related complications, interactions of CCBs with various supplements used by patients, vitamin D and other nutrient deficiencies, and duration of treatment with CCBs. These items should be considered in future trials to draw more robust conclusions about the effectiveness of CCBs in preventing cardiac iron deposition and associated cardiomyopathy in TDT patients.