Mallouppas, M; Chung, R; Ghosh, AK; Macklin, A; Yellon, DM; Walker, JM; (2023) Anthracyclines and Biomarkers of Myocardial Injury: The Effect of Remote Ischemic Conditioning. JACC: CardioOncology , 5 (3) pp. 343-355. 10.1016/j.jaccao.2023.03.008.

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Abstract

Background: Remote ischemic conditioning (RIC) has been beneficial in laboratory studies of anthracycline cardiotoxicity, but its effects in patients is not established. Objectives: The authors studied the effect of RIC on cardiac biomarkers and function during and after anthracycline chemotherapy. Methods: The ERIC-Onc study (Effect of Remote Ischaemic Conditioning in Oncology Patients; NCT02471885) was a randomized, single-blind, sham-controlled study of RIC at each chemotherapy cycle. The primary endpoint was troponin T (TnT) during chemotherapy and up to 1 year. Secondary outcomes included cardiac function, major adverse cardiovascular events (MACE), and MACE or cancer death. Cardiac myosin-binding-protein C (cMyC) was investigated in parallel with TnT. Results: The study was prematurely halted after the evaluation of 55 patients (RIC n = 28, sham n = 27). Biomarkers increased from baseline to cycle 6 of chemotherapy for all patients (median TnT 6 [IQR: 4-9] ng/L to 33 [IQR: 16-36)] ng/L; P ≤ 0.001; cMyC 3 (IQR: 2-5) ng/L to 47 (IQR: 18-49) ng/L; P ≤ 0.001). Mixed-effects regression analysis for repeated measures showed no difference in TnT between the 2 groups (RIC vs sham, mean difference 3.15 ng/L; 95% CI: −0.04 to 6.33; P = 0.053), or cMyC (RIC vs sham, mean difference 4.17 ng/L; 95% CI: −0.12 to 8.45; P = 0.056). There were more MACE and cancer deaths in the RIC group (11 vs 3; HR: 0.25; 95% CI: 0.07-0.90; P = 0.034), with more cancer deaths (8 vs 1; HR: 0.21; 95% CI: 0.04-0.95; P = 0.043) at 1 year. Conclusions: TnT and cMyC significantly increased during anthracycline chemotherapy with 81% having a TnT ≥14 ng/L at cycle 6. RIC did not affect the rise in biomarkers, but there was a small increase in early cancer deaths, possibly related to the greater proportion of patients with metastatic disease randomized to the RIC group (54%vs 37%). (Effect of Remote Ischaemic Conditioning in Oncology Patients [ERIC-ONC]; NCT02471885)

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