Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: primary results of the ARCHER study
Dennis M. McNamara 1,*, Leslie T. Cooper2, Matthias G. Friedrich3,4,5, Yaron Arbel6, Arvind Bhimaraj7,8, Edimar Bocchi9, Andrew Hamer10, Artur Haddad Herdy11, Mathieu Kerneis 12,13, Peter P. Liu14, Andrea B. Parker10, Stuart J. Pocock 15, Eldon R. Smith10, W.H. Wilson Tang16, Guillermo Torre-Amione10,17, and Carsten Tschöpe18,19,20
1 Heart and Vascular Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA; 2Department of Cardiovascular Medicine, Mayo Clinic College of
Medicine and Science, Jacksonville, FL, USA; 3Departments of Medicine and Diagnostic Radiology, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC,
Canada; 4Department of Cardiology, Universitätsklinikum Heidelberg, Heidelberg, Germany; 5Departments of Cardiac Sciences and Radiology, University of Calgary, Calgary, AB, Canada;
6Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel; 7DeBakey Heart & Vascular Center, Houston, TX, USA; 8J.C. Walter Jr. Transplant Center, Houston Methodist Hospital,
Houston, TX, USA; 9Instituto do Coração Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; 10Cardiol Therapeutics Inc., Oakville, ON,
Canada; 11Instituto de Cardiologia de Santa Catarina, São José, Brazil; 12Pitié Salpêtrière Hospital, Sorbonne University, Paris, France; 13ACTION Study Group, Paris, France; 14University of
Ottawa Heart Institute, Ottawa, Canada; 15London School of Hygiene and Tropical Medicine, London, UK; 16Cleveland Clinic, Heart Vascular and Thoracic Institute, Cleveland, OH, USA;
17Instituto de Cardiologia, Hospital Zambrano-Hellion, Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, Mexico; 18Deutsches Herzzentrum der Charité
(DHZC), Clinict of Cardiology, Angiology and Intensive Medicine at Campus Virchow (CVK), Berlin, Germany; 19Berlin Institute of Health (BIH) at Charité—Center for Regenerative
Therapies (BCRT), Berlin, Germany; and 20German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charité University, Berlin, Germany
Affiliationer
Introduction
Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population.
Methods
In a multicentre international double-blind placebo-controlled phase 2 study, we randomly assigned 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV).
Results
All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Baseline mean ECV 38.9 ± 10.9 ml, GLS −15.3 ± 3.6%, and LVEF 60.6 ± 9.9% were consistent with mild to moderate myocarditis and predominantly intact LV function. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of −3.7 ml, confidence interval (CI): −7.4 to 0.1; P = .0538; GLS was −16.0% in the active group and −15.9% in the placebo group, difference of −0.1, CI: −1.2 to 1.1; P = .90. Left ventricular mass was significantly reduced in the active group at 121.1 g compared to placebo 130.3 g, a difference of −9.2, CI: −16.4 to −2.1; P = .0117. In terms of remodelling, LAESV was significantly reduced in the active group (−8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (−7.4 ml; P = .098).
Conclusion
In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. In addition, improvement in other potential markers of myocardial recovery, including a significant reduction in LV mass, was seen in the active treatment group. Further investigation of the therapeutic potential of this therapy in inflammatory cardiac conditions is warranted.
