Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction

被引:121
作者
Mewton, Nathan [1 ,2 ,3 ]
Roubille, Francois [4 ]
Bresson, Didier [5 ]
Prieur, Cyril [1 ,2 ,3 ]
Bouleti, Claire [6 ]
Bochaton, Thomas [1 ,2 ,3 ]
Ivanes, Fabrice [7 ,8 ]
Dubreuil, Olivier [9 ]
Biere, Loic [10 ]
Hayek, Ahmad [1 ,2 ,3 ]
Derimay, Francois [1 ,2 ,3 ]
Akodad, Mariama [4 ]
Alos, Benjamin [6 ]
Haider, Lamis [1 ,2 ,3 ]
El Jonhy, Naoual [1 ,2 ,3 ]
Daw, Rachel [1 ,2 ,3 ]
De Bourguignon, Charles [1 ,2 ,3 ]
Dhelens, Carole [11 ]
Finet, Gerard [1 ,2 ,3 ]
Bonnefoy-Cudraz, Eric [1 ,2 ,3 ]
Bidaux, Gabriel
Boutitie, Florent [12 ,13 ]
Maucort-Boulch, Delphine [12 ]
Croisille, Pierre [14 ]
Rioufol, Gilles [1 ,2 ,3 ]
Prunier, Fabrice [10 ]
Angoulvant, Denis [7 ,8 ]
机构
[1] Hop Cardiovasc & Pneumol Louis Pradel, Clin Invest Ctr, INSERM 1407, Lyon, France
[2] Hosp Civils Lyon, INSERM CarMeN 1060, Lyon, France
[3] Claude Bernard Univ, Lyon, France
[4] Univ Montpellier, PhyMedExp, INSERM, CNRS,Cardiol Dept,CHU Montpellier, Montpellier, France
[5] Univ Hosp Mulhouse, Hop Emile Muller, Cardiol Div, Mulhouse, France
[6] Univ Poitiers, CIC Inserm 1402n, CHU Poitiers, Poitiers, France
[7] CHRU Tours, Cardiol Dept, Tours, France
[8] Tours Univ, EA4245 T2i, Tours, France
[9] Ctr Hosp St Joseph St Luc, Invas Cardiol Dept, Lyon, France
[10] Univ Angers, Cardiol Div, CHU Angers, Inst MITOVASC,CNRS 6015,INSERM U1083, Angers, France
[11] Hosp Civils Lyon, FRIPHARM RC, Pharm Dept, Lyon, France
[12] Hosp Civils Lyon, UMR 5558, CNRS, UCBL,Biostat Dept, Lyon, France
[13] Claude Bernard Univ, IRIS Team, INSERM CarMeN 1060, Lyon, France
[14] CHU St Etienne, Radiol Dept, Univ Hosp, CREATIS CNRS INSERM U1206 Res Lab 5220, St Etienne, France
关键词
clinical trial; colchicine; heart injuries; inflammation; myocardial infarction; thrombosis; ventricular remodeling; INFLAMMATION; TRIAL; CYCLOSPORINE; MECHANISM; PLACEBO; REPAIR; MODEL; SIZE; RISK;
D O I
10.1161/CIRCULATIONAHA.121.056177
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: Inflammation is a key factor of myocardial damage in reperfused ST-segment-elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment-elevation myocardial infarction. METHODS: In this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment-elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes. RESULTS: We enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement-defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16-44] versus 28.4 IQR [14-40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, -8.3% to 11.1%) versus -1.1% (IQR, -8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10-28] versus 18 IQR [10-27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002). CONCLUSIONS: In this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging.
引用
收藏
页码:859 / 869
页数:11
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