title: Hydroxychloroquine for the prevention of recurrent cardiovascular events in myocardial infarction patients: rationale and design of the OXI trial.
abstract: Inflammation of the arterial wall plays a central role in the pathogenesis of atherosclerosis. Among patients with rheumatic diseases, anti-rheumatic medication reduces the incidence of cardiovascular (CV) diseases, but only few studies have addressed their cardioprotective effects on patients with no rheumatic diseases. Hydroxychloroquine (HCQ) is an anti-rheumatic drug commonly used in the treatment of rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol levels and the risk of type II diabetes, and has also anti-platelet effects.
  
  
  
  The OXI trial is an event-driven trial that will randomize 2500 patients hospitalized for myocardial infarction (MI). Participants will receive active HCQ or placebo for at least 12 months, and until 350 CV events are confirmed. The primary trial endpoint is the composite of death, MI, hospitalization for unstable angina, urgent percutaneous coronary intervention, and urgent coronary artery bypass grafting. Secondary trial endpoints are the primary end point plus stroke, the effect of HCQ treatment on lipids, on the incidence of Type 2 diabetes, on the level of haemoglobin A1c, and on inflammatory parameters. A 6 months placebo-controlled safety pilot trial with 200 patients is currently ongoing to assess the safety of HCQ in the setting of MI.
  
  
  
  The OXI trial will determine whether treatment with HCQ, as compared with placebo, will reduce recurrent CV events among MI patients. If positive, then the OXI trial would provide an entirely novel multitarget approach for the secondary prevention of atherosclerotic cardiovascular diseases (ACVD).
authors.affiliation: Heart and Lung Center, University of Helsinki and Helsinki University Hospital, PL 340, 00029 HUS, Finland.
authors.forename: Otto
authors.initials: O
authors.lastname: Hartman
authors.affiliation: Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.affiliation: Heart and Lung Center, University of Helsinki and Helsinki University Hospital, PL 340, 00029 HUS, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Lehtonen
authors.affiliation: Department of Rheumatology, University of Helsinki and Helsinki University Hospital, PL 340, 00029 HUS, Helsinki, Finland.
authors.forename: Kari K
authors.initials: KK
authors.lastname: Eklund
authors.affiliation: Heart and Lung Center, University of Helsinki and Helsinki University Hospital, PL 340, 00029 HUS, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000150:complications*; D010865:Pilot Projects; D012008:Recurrence; D055502:Secondary Prevention / Q000379:methods*
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine
keywords: Acute coronary syndrome; Anti-inflammatory; Atherosclerosis; Coronary artery disease; Hydroxychloroquine; Myocardial infarction; inflammation