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Randomized Controlled Trial
. 2023 Aug 8;330(6):528-536.
doi: 10.1001/jama.2023.11887.

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial

Tomas G Neilan  1   2 , Thiago Quinaglia  1 , Takeshi Onoue  3 , Syed S Mahmood  1 , Zsofia D Drobni  4 , Hannah K Gilman  1 , Amanda Smith  3 , Julius C Heemelaar  1 , Priya Brahmbhatt  3 , Jor Sam Ho  1 , Supraja Sama  1 , Jakub Svoboda  5 , Donna S Neuberg  6 , Jeremy S Abramson  7 , Ephraim P Hochberg  7 , Jefferey A Barnes  7 , Philippe Armand  8 , Eric D Jacobsen  8 , Caron A Jacobson  8 , Austin I Kim  8 , Jacob D Soumerai  7 , Yuchi Han  3 , Robb S Friedman  7 , Ann S Lacasce  8 , Bonnie Ky  3 , Dan Landsburg  5 , Sunita Nasta  5 , Raymond Y Kwong  9 , Michael Jerosch-Herold  10 , Robert A Redd  6 , Lanqi Hua  2   11 , James L Januzzi  2   12 , Aarti Asnani  13 , Negareh Mousavi  14 , Marielle Scherrer-Crosbie  3
Affiliations
Randomized Controlled Trial

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial

Tomas G Neilan et al. JAMA. .

Abstract

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use.

Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.

Design, setting, and participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.

Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months.

Main outcomes and measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.

Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups.

Conclusions and relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.

Trial registration: ClinicalTrials.gov Identifier: NCT02943590.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Neilan reported receipt of personal fees for consulting from Bristol Myers Squibb; receipt of personal fees from Genentech, Roche, Sanofi, C4 Therapeutics, CardiolRx, and CRC Oncology; and receipt of grants from Bristol Myers Squibb and AstraZeneca. Dr Mahmood reported receipt of personal fees from AltaThera and Nektar Therapeutics. Dr Abramson reported receipt of personal fees from Celgene, Incyte, Takeda, Janssen, Genentech, Eli Lilly, Kite Pharma, AbbVie, AstraZeneca, Epizyme, Genmab, Century Therapeutics, Regeneron, MorphoSys, BeiGene, Mustang Bio, Ono Pharma, Kymera, Bluebird Bio, C4 Therapeutics, Caribou Biosciences, Interius, Cellectar, and Bristol Myers Squibb and receipt of grants from Bristol Myers Squibb, Seattle Genetics, Mustang Bio, Cellectis, and Merck. Dr Armand reported consulting for Merck, Bristol Myers Squibb, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, AstraZeneca, Genentech/Roche, Xencor, and Foresight; receipt of research funding/grants from Merck, Bristol Myers Squibb, Affimed, Adaptive, Tensha, Otsuka, Sigma Tau, Genentech/Roche, IGM, AstraZeneca, and Kite; and receipt of honoraria from Merck. Dr Jacobsen reported receipt of personal fees from Merck, Celgene, Beigene, Daiichi, Novartis, Pharmacyclics, Janssen, AstraZeneca, and Bayer and receipt of grants from Merck. Dr Jacobson reported receipt of personal fees from Kite/Gilead, Novartis, Bristol Myers Squibb/Celgene, Instil Bio, Abintus Bio, Caribou Bio, ImmPACT Bio, Daiichi-Sankyo, AstraZeneca, Morphosys, ADC Therapeutics, AbbVie, Miltenyi, and Synthekine. Dr Soumerai reported receipt of personal fees for consulting from AstraZeneca, AbbVie, Beigene, Biogen, Roche/Genentech, Verastem, and TG Therapeutics and receipt of research support paid to his institution from Bristol Myers Squibb, Seattle Genetics, Adaptive Biotechnologies, BostonGene, GlaxoSmithKline, Moderna, and Takeda. Dr Han reported receipt of personal fees for consulting from Vertex Inc. Dr Ky reported consulting for Bristol Myers Squibb, AstraZeneca, Roche, and Pfizer; receipt of grants from Pfizer, the National Institutes of Health, and the American Heart Association; and serving as editor for the American College of Cardiology. Dr Januzzi reported being a trustee of the American College of Cardiology, a board member of Imbria Pharmaceuticals, and a director at Jana Care; receipt of grants from Abbott Diagnostics, Applied Therapeutics, Innolife, Novartis Pharmaceuticals, and Roche Diagnostics; receipt of personal fees for consulting from Abbott, Beckman, Bristol Myers Squibb, Cytokinetics, Janssen, Novartis Pharmaceuticals, Prevencio, Roche Diagnostics and Siemens; and participation in clinical end-point committees/data and safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Intercept, Pfizer, Siemens, and Takeda. No other disclosures were reported.

Figures

Figure.
Figure.. Participant Flow in the STOP-CA Trial
See this image and copyright information in PMC

Comment in

References

    1. Lyon AR, López-Fernández T, Couch LS, et al. ; ESC Scientific Document Group . 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi: 10.1093/eurheartj/ehac244 - DOI - PubMed
    1. Hequet O, Le QH, Moullet I, et al. Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. J Clin Oncol. 2004;22(10):1864-1871. doi: 10.1200/JCO.2004.06.033 - DOI - PubMed
    1. Limat S, Demesmay K, Voillat L, et al. Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2003;14(2):277-281. doi: 10.1093/annonc/mdg070 - DOI - PubMed
    1. Riad A, Bien S, Westermann D, et al. Pretreatment with statin attenuates the cardiotoxicity of doxorubicin in mice. Cancer Res. 2009;69(2):695-699. doi: 10.1158/0008-5472.CAN-08-3076 - DOI - PubMed
    1. Ramanjaneyulu SV, Trivedi PP, Kushwaha S, Vikram A, Jena GB. Protective role of atorvastatin against doxorubicin-induced cardiotoxicity and testicular toxicity in mice. J Physiol Biochem. 2013;69(3):513-525. doi: 10.1007/s13105-013-0240-0 - DOI - PubMed

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