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JACC CardioOncol
JACC CardioOncol
JACC: CardioOncology
2666-0873
Elsevier

S2666-0873(24)00207-2
10.1016/j.jaccao.2024.05.011
Letters
To the Editor
Reply
Assessing Neurohormonal Antagonist Withdrawal in HER2+ Breast Cancer Patients With CTRCD
Yu Christopher MBBS @drchrisyu

Thavendiranathan Paaladinesh MD, SM @dineshpmcc1
dinesh.thavendiranathan@uhn.ca
∗
∗ Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G2 2N2, Canada @dineshpmcc1dinesh.thavendiranathan@uhn.ca
25 6 2024
8 2024
25 6 2024
6 4 627627
© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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pmcWe thank Drs Albulushi and Al-Farhan for their interest in our recent work and summarizing our findings in a table format.1 With respect to the selection criteria, as described in our work, the patients requested to stop their neurohormonal antagonists (NHAs) because of fatigue or pill burden. From our center’s experience and engaging with other cardio-oncologists, we believe that this reflects a broader patient perspective. In fact, our recent International Cardio-Oncology Society survey of clinicians taking care of patients with cancer revealed that 98% of 102 participants believed that studying the safety of withdrawing NHAs in patients with recovered cancer therapy–related cardiac dysfunction is important (unpublished data).

Second, we agree with the comments about the generalizability of the findings given the study limitations. This is particularly the reason that we state in our manuscript that the findings are hypothesis generating and motivate future randomized controlled trials. Based on these encouraging findings, we designed The STOP-MED CTRCD (Multi-Centre Non-Inferiority Randomized Controlled Trial of STOPping Cardiac MEDications in Patients with Normalized Cancer Therapy Related Cardiac Dysfunction; NCT06183437), which is currently recruiting. We will be assessing the long-term safety of stopping heart failure medication by following patients for 5 years. We aim to recruit 335 patients from centers in Canada, Australia, United Kingdom, and United States. In addition, there are also 2 other randomized controlled trials that are currently recruiting to answer a similar question: 1) the COP-RCT (Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardiotoxicity; ANZCTR12621000928819)2; and 2) the HER-SAFE (Safety of Withdrawal of Pharmacological Treatment for Recovered HER2 Targeted Therapy Related Cardiac Dysfunction; NCT05880160).

Lastly, we agree that cancer cohorts are different to patients enrolled in TRED-HF3 given that with the cancer cohorts, the cause of the cardiac dysfunction is known, the causative agent (cancer therapy) is completed, the nadir of left ventricular ejection fraction is commonly not as severe as those in TRED-HF, and cardiac medications are started early after diagnosis.

In conclusion, our hypothesis-generating work will be followed by larger-scale randomized controlled trials providing evidence in this field over the next few years. The need to generate high-quality data in cardio-oncology is an essential future direction that requires a collaborative multicenter approach.

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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References

1 Yu C. Power C. Sooriyakanthan M. Withdrawal of neurohormonal antagonists in breast cancer patients with cardiotoxicity and improved left ventricular function J Am Coll Cardiol CardioOnc 6 2 2024 315 317
2 Yu C. Negishi T. Pathan F. Rationale and design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): a pilot study Heart Lung Circ 33(5) 2024 753 757 10.1016/j.hlc.2023.10.004 37949748
3 Halliday B.P. Wassall R. Lota A.S. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial Lancet 393 10166 2019 61 73 10.1016/S0140-6736(18)32484-X 30429050
