Impact on clinical outcomes of renin-angiotensin system inhibitors against doxorubicin-related toxicity in patients with breast cancer and hypertension: A nationwide cohort study in South Korea.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Breast Neoplasms*/complications ; Breast Neoplasms*/drug therapy ; Breast Neoplasms*/chemically induced ; Hypertension*/chemically induced ; Hypertension*/drug therapy ; Heart Failure*; Humans ; Female ; Antihypertensive Agents/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/adverse effects ; Renin-Angiotensin System ; Cohort Studies ; Doxorubicin/adverse effects ; Enzyme Inhibitors/pharmacology ; Angiotensin Receptor Antagonists/adverse effects

Background: Although doxorubicin (DOX) is a commonly used potent chemotherapeutic agent in patients with breast cancer, its cardiotoxic effect is a concern, particularly in patients with hypertension. Antihypertensive renin-angiotensin system (RAS) inhibitors may potentially play a role in preventing overt heart failure (HF) due to DOX toxicity. This study aimed to evaluate whether the use of RAS inhibitors improves clinical outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy.
Methods: A total of 54,344 female patients who were first diagnosed with breast cancer and initiated into DOX therapy between 2008 and 2015 were recruited from a nationwide Korean cohort. Patients were divided into two groups: with and without hypertension (HT, n = 10,789; non-HT, n = 43,555), and the RAS inhibitor group (n = 1,728) was sub-classified from the HT group. Two propensity score-matched cohorts were constructed to compare the clinical outcomes between non-HT and HT groups and between non-HT and RAS inhibitor groups. The primary outcome was the composite of HF and death.
Results: After propensity score matching, the HT group had a higher risk for HF (adjusted hazard ratio [HR] = 1.30, 95% confidence intervals [95% CI] = 1.09-1.55) compared to the non-HT group, but there was no significant difference in primary outcome between the two groups. The RAS inhibitor group had a lower risk for primary outcome (adjusted HR = 0.78, 95% CI = 0.65-0.94) and death (adjusted HR = 0.81, 95% CI = 0.66-0.99) compared to the non-HT group.
Conclusions: Hypertension is a risk factor for HF in patients with breast cancer undergoing DOX chemotherapy. However, the RAS inhibitors used to treat hypertension may contribute to decreased mortality and improved clinical outcomes.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Hwang, Lee. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Circulation. 2022 May 3;145(18):e895-e1032. (PMID: 35363499)
J Intern Med. 2001 Mar;249(3):253-61. (PMID: 11285045)
Clin Hypertens. 2023 Aug 15;29(1):22. (PMID: 37580841)
J Clin Oncol. 2008 Jul 1;26(19):3159-65. (PMID: 18591554)
Eur Heart J. 2016 Sep 21;37(36):2768-2801. (PMID: 27567406)
Eur Heart J. 2016 Jun 1;37(21):1671-80. (PMID: 26903532)
Ann Oncol. 2015 Jun;26(6):1128-1133. (PMID: 25795198)
Cancer. 2003 Jun 1;97(11):2869-79. (PMID: 12767102)
J Chemother. 2016 Aug;28(4):314-20. (PMID: 26138656)
Toxicology. 1994 Sep 6;92(1-3):179-92. (PMID: 7940559)
Jpn J Pharmacol. 2002 Feb;88(2):183-8. (PMID: 11928719)
JAMA. 1996 May 22-29;275(20):1557-62. (PMID: 8622246)
Mayo Clin Proc. 2014 Sep;89(9):1287-306. (PMID: 25192616)
PLoS One. 2012;7(11):e48771. (PMID: 23152801)
Acta Oncol. 2011 May;50(4):569-73. (PMID: 21208033)
Eur J Cancer Prev. 2017 Jan;26(1):78-85. (PMID: 27158979)
J Breast Cancer. 2023 Oct;26(5):492-503. (PMID: 37704380)
J Am Soc Hypertens. 2014 Nov;8(11):791-9. (PMID: 25455004)
Biochim Biophys Acta. 2016 Jun;1863(6 Pt A):1071-81. (PMID: 26975580)
J Transl Med. 2020 Dec 9;18(1):470. (PMID: 33298102)
Acta Pharmacol Sin. 2011 Nov;32(11):1345-50. (PMID: 21963897)
J Transl Med. 2019 Jul 19;17(1):229. (PMID: 31324258)
Circulation. 2006 Dec 5;114(23):2474-81. (PMID: 17101852)
J Am Coll Cardiol. 2013 Jun 11;61(23):2355-62. (PMID: 23583763)
Aging (Albany NY). 2019 Jun 19;11(12):3969-3992. (PMID: 31219799)
J Cell Physiol. 2018 Jan;233(1):463-475. (PMID: 28295305)
Circulation. 2012 Dec 4;126(23):2749-63. (PMID: 23212997)
Lancet Oncol. 2013 Nov;14(12):1233-42. (PMID: 24140184)
Cancer Invest. 2011 Nov;29(9):585-93. (PMID: 21936625)
Heart Fail Rev. 2021 Jan;26(1):101-109. (PMID: 31900787)
J Clin Hypertens (Greenwich). 2014 Mar;16(3):177-85. (PMID: 24621095)
Breast Cancer Res Treat. 2011 Sep;129(2):549-56. (PMID: 21479924)
J Cardiovasc Pharmacol. 2004 Nov;44(5):615-21. (PMID: 15505501)
Clin Genitourin Cancer. 2017 Jun;15(3):384-390.e3. (PMID: 28089721)
Heart Fail Rev. 2022 Jan;27(1):295-319. (PMID: 32472524)
Clin Cancer Res. 2015 Jun 1;21(11):2471-9. (PMID: 25724518)
Intern Emerg Med. 2021 Mar;16(2):477-486. (PMID: 33011930)
Ann Oncol. 2007 Jun;18(6):1117. (PMID: 17586751)
Front Endocrinol (Lausanne). 2021 Sep 03;12:736361. (PMID: 34539580)
Free Radic Res. 2010 Nov;44(11):1369-77. (PMID: 20815778)
Front Oncol. 2021 Apr 01;11:664741. (PMID: 33869068)
J Hum Hypertens. 2020 Oct;34(10):673-681. (PMID: 32747676)
Eur Heart J. 2022 Nov 1;43(41):4229-4361. (PMID: 36017568)
Tumour Biol. 2015 Feb;36(2):893-900. (PMID: 25304158)

0 (Antihypertensive Agents)
0 (Angiotensin-Converting Enzyme Inhibitors)
80168379AG (Doxorubicin)
0 (Enzyme Inhibitors)
0 (Angiotensin Receptor Antagonists)

Date Created: 20231120 Date Completed: 20231122 Latest Revision: 20231129

20231215

PMC10659172

10.1371/journal.pone.0294649

37983233