Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.

Heinz Drexel, Andreea Ivanescu, Ágnes M Paál, Nabil V Sayour, Gianluigi Savarese, Filippo Crea, Anne Grete Semb, Ioanna Andreadou, Erik Lerkevang Grove, Gheorghe Andrei Dan, Antonella Lombardo, Dobromir Dobrev, Rudolf A de Boer, Pietro Ameri, Wouter C Meijers, Giorgio Minotti, Zoltán V Varga, Juan-Carlos Kaski, Péter Ferdinandy, Massimiliano Camilli

Journal: European heart journal 2024;45(14):1224-1240

PMID: 38441940

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Abstract

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.

Address: Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1085 Budapest, Üllői út 26, Hungary.; HCEMM-SU Cardiometabolic Immunology Research Group, H-1089 Budapest, Nagyvárad tér 4, Hungary.; MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, H-1089 Budapest, Nagyvárad tér 4, Hungary.; Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1085 Budapest, Üllői út 26, Hungary.; Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Italian IRCCS Cardiology Network, Genova, Italy.; Department of Internal Medicine, University of Genova, Genova, Italy.; Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands.; University Campus Bio-Medico, Via Álvaro del Portillo, 21, 00128 Rome, Italy.; Laboratory of Pharmacology, School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.; Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy.; Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Vorarlberg Institute for Vascular Investigation & Treatment (VIVIT), Carinagasse 47, A-6800 Feldkirch, Austria.; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.; Carol Davila University of Medicine and Pharmacy, Colentina University Hospital, Bucharest, Romania.; Cardiology Department, Colentina Clinical Hospital, Bucharest, Romania.; Division of Research and Innovation, REMEDY-Centre for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway.; Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.; Heart and Vascular and Neuro Theme, Karolinska University Hospital, Stockholm, Sweden.; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.; Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Montréal, QC, Canada.; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.; Molecular and Clinical Sciences Research Institute, St. George's University of London, London, United Kingdom.; Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1085 Budapest, Üllői út 26, Hungary.; Pharmahungary Group, Szeged, Hungary.; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.

DOI: 10.1093/eurheartj/ehae105