Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

David Austin; Rebecca H Maier; Nasima Akhter; Mohammad  Sayari; Emmanuel Ogundimu; Jamie Maddox; Sharareh Vahabi; Alison C.  Humphreys; Janine  Graham; Helen Oxenham; Sophie Haney; Nicola Cresti; Mark Verrill; Wendy  Osborne; Kathryn L.  Wright; Rebecca  Goranova; James R.  Bailey; Nagesh  Kalakonda; Mac  Macheta; Mari F.  Kilner; Moya E.  Young; Nick J.  Morley; Pratap  Neelakantan; Georgia  Gilbert; Byju K.  Thomas; Richard J.  Graham; Takeshi  Fujisawa; Nicholas L.  Mills; Victoria  Hildreth; Jonathan  Prichard; Adetayo S Kasim; Helen C Hancock; Chris Plummer

doi:10.1016/j.jaccao.2024.07.010

Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

David Austin, Rebecca H Maier, Nasima Akhter, Mohammad Sayari, Emmanuel Ogundimu, Jamie Maddox, Sharareh Vahabi, Alison C. Humphreys , Janine Graham, Helen Oxenham, Sophie Haney, Nicola Cresti, Mark Verrill, Wendy Osborne, Kathryn L. Wright, Rebecca Goranova, James R. Bailey, Nagesh Kalakonda , Mac Macheta, Mari F. KilnerMoya E. Young , Nick J. Morley , Pratap Neelakantan , Georgia Gilbert , Byju K. Thomas, Richard J. Graham , Takeshi Fujisawa , Nicholas L. Mills, Victoria Hildreth, Jonathan Prichard, Adetayo S Kasim, Helen C Hancock, Chris Plummer

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Abstract

Background
Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.
Objectives
The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.
Methods
This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.
Results
Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.
Conclusions
Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)

Original language	English
Journal	JACC: CardioOncology
DOIs	https://doi.org/10.1016/j.jaccao.2024.07.010
Publication status	Published - 27 Aug 2024

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Austin, D., Maier, R. H., Akhter, N., Sayari, M., Ogundimu, E., Maddox, J., Vahabi, S., Humphreys , A. C., Graham, J., Oxenham, H., Haney, S., Cresti, N., Verrill, M., Osborne, W., Wright, K. L., Goranova, R., Bailey, J. R., Kalakonda , N., Macheta, M., ... Plummer, C. (2024). Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial. JACC: CardioOncology. https://doi.org/10.1016/j.jaccao.2024.07.010

@article{4d6c407e35134360887a988bea554fd6,

title = "Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial",

abstract = "BackgroundCardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.ObjectivesThe PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.MethodsThis prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.ResultsMyocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.ConclusionsAdding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)",

author = "David Austin and Maier, {Rebecca H} and Nasima Akhter and Mohammad Sayari and Emmanuel Ogundimu and Jamie Maddox and Sharareh Vahabi and Humphreys, {Alison C.} and Janine Graham and Helen Oxenham and Sophie Haney and Nicola Cresti and Mark Verrill and Wendy Osborne and Wright, {Kathryn L.} and Rebecca Goranova and Bailey, {James R.} and Nagesh Kalakonda and Mac Macheta and Kilner, {Mari F.} and Young, {Moya E.} and Morley, {Nick J.} and Pratap Neelakantan and Georgia Gilbert and Thomas, {Byju K.} and Graham, {Richard J.} and Takeshi Fujisawa and Mills, {Nicholas L.} and Victoria Hildreth and Jonathan Prichard and Kasim, {Adetayo S} and Hancock, {Helen C} and Chris Plummer",

year = "2024",

month = aug,

day = "27",

doi = "10.1016/j.jaccao.2024.07.010",

language = "English",

journal = "JACC: CardioOncology",

issn = "2666-0873",

publisher = "Elsevier",

}

Austin, D, Maier, RH, Akhter, N, Sayari, M, Ogundimu, E, Maddox, J, Vahabi, S, Humphreys , AC, Graham, J, Oxenham, H, Haney, S, Cresti, N, Verrill, M, Osborne, W, Wright, KL, Goranova, R, Bailey, JR, Kalakonda , N, Macheta, M, Kilner, MF, Young , ME, Morley , NJ, Neelakantan , P, Gilbert , G, Thomas, BK, Graham , RJ, Fujisawa , T, Mills, NL, Hildreth, V, Prichard, J, Kasim, AS, Hancock, HC & Plummer, C 2024, 'Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial', JACC: CardioOncology. https://doi.org/10.1016/j.jaccao.2024.07.010

TY - JOUR

T1 - Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

AU - Austin, David

AU - Maier, Rebecca H

AU - Akhter, Nasima

AU - Sayari, Mohammad

AU - Ogundimu, Emmanuel

AU - Maddox, Jamie

AU - Vahabi, Sharareh

AU - Humphreys , Alison C.

AU - Graham, Janine

AU - Oxenham, Helen

AU - Haney, Sophie

AU - Cresti, Nicola

AU - Verrill, Mark

AU - Osborne, Wendy

AU - Wright, Kathryn L.

AU - Goranova, Rebecca

AU - Bailey, James R.

AU - Kalakonda , Nagesh

AU - Macheta, Mac

AU - Kilner, Mari F.

AU - Young , Moya E.

AU - Morley , Nick J.

AU - Neelakantan , Pratap

AU - Gilbert , Georgia

AU - Thomas, Byju K.

AU - Graham , Richard J.

AU - Fujisawa , Takeshi

AU - Mills, Nicholas L.

AU - Hildreth, Victoria

AU - Prichard, Jonathan

AU - Kasim, Adetayo S

AU - Hancock, Helen C

AU - Plummer, Chris

PY - 2024/8/27

Y1 - 2024/8/27

N2 - BackgroundCardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.ObjectivesThe PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.MethodsThis prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.ResultsMyocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.ConclusionsAdding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)

AB - BackgroundCardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.ObjectivesThe PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.MethodsThis prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.ResultsMyocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.ConclusionsAdding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)

U2 - 10.1016/j.jaccao.2024.07.010

DO - 10.1016/j.jaccao.2024.07.010

M3 - Article

SN - 2666-0873

JO - JACC: CardioOncology

JF - JACC: CardioOncology

ER -

Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

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