Lotta Ulander1, Heli Tolppanen1, Otto Hartman1, Tuomas T Rissanen2, Riitta Paakkanen1, Jouni Kuusisto1, Olli Anttonen3, Tuomo Nieminen3, Jaana Yrjölä4, Ransu Ryysy4, Teemu Drews5, Seppo Utriainen5, Pasi Karjalainen1, Ismo Anttila6, Katariina Nurmi7, Kristiina Silventoinen7, Miika Koskinen8, Petri T Kovanen9, Jukka Lehtonen1, Kari K Eklund7, Juha Sinisalo10. 1. Heart and Lung Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland. 2. Heart Center, North Karelia Central Hospital, Siunsote, Joensuu, Finland. 3. Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland. 4. Department of Internal Medicine, Kymenlaakson Central Hospital, Kotka, Finland. 5. Department of Internal Medicine, South Karelia Central Hospital, Lappeenranta, Finland. 6. Department of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland. 7. Department of Rheumatology, Helsinki University Hospital, Helsinki University, ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland. 8. Helsinki Biobank, Helsinki University Hospital, Helsinki University, Helsinki, Finland. 9. Wihuri Research Institute, Biomedicum, Helsinki, Finland. 10. Heart and Lung Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland. Electronic address: juha.sinisalo@hus.fi.
Abstract
OBJECTIVES: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. METHOD: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. RESULTS: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). CONCLUSIONS: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.
RCT Entities:
OBJECTIVES: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. METHOD: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarctionpatients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. RESULTS: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). CONCLUSIONS: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.