Epigallocatechin-3-gallate tolerability and impact on survival in a cohort of patients with transthyretin-related cardiac amyloidosis. A single-center retrospective study

Abstract

Transthyretin-related (ATTR) cardiac amyloidosis is currently lacking a disease-modifying therapy. Despite demonstration of effectiveness in halting amyloid deposition, no study focused on epigallocatechin-3-gallate (EGCG) impact on patient survival. We sought to explore prognostic impact of EGCG in a cohort of lone cardiac ATTR patients. From the Florence Tuscan Regional Amyloid Centre database, we retrospectively selected ATTR patients treated with EGCG (675mg daily dose) for a minimum of 9 months, between March 2013 and December 2016. As a control group, we selected ATTR patients who received guideline-directed medical therapy alone. End point of the study was time to all cause death or cardiac transplantation. Sixty-five patients (30 treatment groups vs. 35 control groups) had a median follow-up of 691 days. There were no differences in baseline characteristics between groups. Five deaths occurred in EGCG group versus eight in control group; one patient underwent effective cardiac transplantation in EGCG group. There was no difference in survival estimates between EGCG and control group (60 ± 15% vs. 61 ± 12%, p = 0.276). EGCG was well tolerated, without major safety concerns. In a real-world cohort of ATTR patients with lone cardiac involvement, EGCG was a safe therapeutic option, but was not associated with survival improvement.

CCS/CHFS Heart Failure Guidelines: Clinical Trial Update on Functional Mitral Regurgitation, SGLT2 Inhibitors, ARNI in HFpEF, and Tafamidis in Amyloidosis

“…Different therapeutic modalities have been investigated in recent years using transthyretin stabilizers (eg, diflunisal and tafamidis), suppressors of ATTR synthesis (gene silencers), and amyloid fibrils degraders (doxycycline with tauroursodeoxycholic acid or ursodeoxycholic acid and epigallocatechin 3-gallate found in green tea extracts). [28][29][30][31][32][33] Historically, 31 most studies that have investigated these drugs have been small and observational in nature and used surrogate end points. The recently published Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) randomized 441 patients with wild type or mutant (hereditary) ATTR-CA to either tafamidis, a transthyretin tetramer stabilizer, or placebo, and were followed for 30 months.…”

<p>Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors</p>

“…98 In addition, EGCG stabilizes myocardial mass in wtATTR-CM patients with good tolerance and no major safety concerns. 99,100 Therefore, EGCG has been expected to be developed for the treatment of amyloid cardiomyopathy. In vitro, studies have shown that resveratrol may promote free monomers to form a tetramer and decrease the toxicity of pre-fiber TTR molecules.…”

Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

“…55 However, results from a single-center retrospective study suggested that EGCG, although a safe therapeutic option, was not associated with improved survival. 56 No clinical trial of EGCG as a treatment for ATTR has been conducted to date. 57…”

“…In a phase 2 trial, daily oral EGCG was used to treat AL amyloidosis, with favorable clinical efficacy and low toxicity 55 . However, results from a single‐center retrospective study suggested that EGCG, although a safe therapeutic option, was not associated with improved survival 56 . No clinical trial of EGCG as a treatment for ATTR has been conducted to date 57…”