International randomized trial on the effect of revascularization or optimal medical therapy of chronic total coronary occlusions with myocardial ischemia - ISCHEMIA-CTO trial -- rationale and design

Background Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone. Methods This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter [greater than or equal to] 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization. Implications This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO. Author Affiliation: (1) Sahlgrenska University Hospital, Gothenburg, Sweden (2) Dept. Cardiology Aarhus University Hospital, Skejby, Denmark (3) Dept. of Cardiology, Aalborg University Hospital, Aalborg, Denmark (4) Hospital Universitario Clíníco San Carlos, Madrid, Spain (5) Cardiology Department, Belfast Health & Social Care Trust Belfast, Northern Ireland, United Kingdom (6) Edinburgh Royal Infirmary, Edinburgh, United Kingdom (7) Odense University Hospital, Odense, Denmark (8) Rigshospitalet, Copenhagen, Denmark (9) Zealand University Hospital, Roskilde, Denmark (10) Copenhagen University Hospital -- Herlev and Gentofte, Copenhagen, Denmark (11) Tays Heart Hospital and Tampere University, Tampere, Finland (12) Cardiovascular Institute, Groupe Hospitalier Mutualiste, Grenoble, France (13) North-Estonia Medical Centre, Tallinn, Estonia * Corresponding author: Emil Nielsen Holck, Dept. Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark 8200 Article History: Received 27 September 2022; Accepted 15 November 2022 (footnote)# ENH and TR contributed equally. Byline: Truls Råmunddal, MD, PhD (1,#), Emil Nielsen Holck, MD [eh@clin.au.dk] (2,#,*), Salma Karim, MD (2), Ashkan Eftekhari, MD PhD (3), Javier Escaned, MD PhD (4), Dan Ioanes, MD (1), Simon Walsh, MD (5), James Spratt, MD DMSc (6), Karsten Veien, MD PhD (7), Lisette Okkels Jensen, MD PhD DMSci (7), Hans-Henrik Tilsted, MD PhD (8), Christian Juhl Terkelsen, MD PhD (2), Ole Havndrup, MD PhD (9), Niels Thue Olsen, MD PhD (10), Olli A. Kajander, MD PhD (11), Benjamin Faurie, MD (12), Peep Lanematt, MD PhD (13), Lars Jakobsen, MD PhD (2), Evald Høj Christiansen, MD PhD (2)