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Lancet. 2008 May 24;371(9626):1761-8. doi: 10.1016/S0140-6736(08)60763-1.

Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial.

Collaborators (270)

Tardif JC, Pfeffer M, McMurray J, Klug E, Chaitman B, Alderman E, Fisher L, Rouleau J, Waters D, Cloherty E, Duong C, Lewis E, Mercier R, Solomon S, Anderson T, Arnold JM, Bedard J, Bhargava R, Bose S, Chehayeb R, Cohen E, Constance C, DeGrace M, Dion D, Douketis J, Ducas J, Fay D, Fortin C, Gebhardt V, Gendreau R, Gin K, Gosselin G, Grandmont D, Hess A, Hui W, Huynh TT, Kouz S, Lai C, Matangi M, Morris A, Nasmith J, Nault P, Nigro F, Pandey AS, Pesant Y, Petrella R, Poirier P, Pouliot J, Quinn B, Quintin I, Rajakumar A, Rinfret S, Rupka D, Sabbah E, Savard D, Schampaert E, Sussex B, Syan G, Talbot P, Tardif JC, Timothee JR, Title L, Tremblay G, Vakani MT, Vexler R, Badenhorst C, Bedhesi S, Bester FC, Bodenstein WM, Burgess L, Cassel G, Dawood SY, Ebrahim I, Essop MR, Jankelow P, Jeena CP, Ker AM, King J, Klug E, Lamparelli R, Lloyd E, Mabin T, Moodley R, Naidu RK, Ramdass AS, Roux P, Saaiman JA, Sareli P, Sarvan MI, Singh V, Snyders A, Tayob FI, Theron H, Viljoen J, Wittmer H, Ahsan A, Batin P, Boon N, Bridges A, Brooksby P, Channer K, Dunn F, Findlay I, Hillis G, Hudson I, Jacob A, Kadr HB, Lip G, McMurray J, Murdoch D, Nolan J, Ray S, Schofield P, Shah A, Squire I, Tan LB, Wheeldon N, Abel P, Ackell P, Alexander S, Amkieh A, Anderson J, Andreae G, Ashby C, Bach R, Bank A, Baron S, Becker J, Bedoya R, Bernstein M, Bethala V, Bhalla R, Bilazarian S, Bittner V, Bleyer F, Block P, Bouchard A, Breisblatt W, Brockington G, Brown C, Brown C, Brown C, Carstens J, Chambers J, Changlani M, Chu A, Cole J, Connelly T, Corbelli JC, Corder CN, Coto HA, Denny M, Denys B, Desai V, Devlin W, Diez J, Dionisopoulos P, Doelle GC, Doris JF, Downey W, Dykstra G, East C, El Shahawy M, Ellis J, Fialkow J, Fierer R, Fischell T, Fleet W, Gabriel G, Gammon R, George W, Gilmore R, Glass M, Goldscher D, Goldstein M, Gorwit J, Gottlieb D, Goulah R, Griffen JJ, Grossman W, Hackworth JN, Halpern S, Haque I, Harrison WR, Haskel E, Haught H, Heinsimer J, Hibbard MH, Hilton T, Hinchman D, Hodes Z, Ibrahim H, Idarraga S, Jackson B, Jerome S, Judy L, Kakavas P, Kassell D, Kelemen M, Kereiakes DJ, Kerut EK, Kleiman N, Knopp R, Kogan A, Kopecky SL, Koren M, Kosinski EJ, Kozman H, Kramer JH, Lang J, Lemlek JE, Litt M, Logsdon J, Lurie M, Madder R, Marple R, Massaro J, Mazza J, McGarvey J, McGrew F, Menapace F, Merlino J, Milas J, Miller D, Miller LA, Mirro MJ, Mohiuddin S, Muhlestein JB, Myers G, Nallasivan M, Nash S, Neutel J, Niazi IK, OBryan JP, Ong S, Pasquini J, Pearson AC, Perlstein E, Peters P, Phillips D, Pierce K, Porterfield J, Ptacin MJ, Quartner JL, Ritzer T, Rivera E, Roth EM, Schang S, Schneider R, Schussheim A, Shogry R, Short WG, Silver GM, Silverberg B, Smith K, Sotolongo CM, Sotolongo R, Staniloae CS, Stillabower ME, Sundaran S, Treasure CB, Underwood H, Vijay NK, Voyles WF, Weiss RJ, Whitney R, Wickemeyer WJ, Williams J, Yount RD, Zebrack J.

Author information

  • 1Montreal Heart Institute, University of Montreal, Montreal, Canada. jean-claude.tardif@icm-mhi.org

Abstract

BACKGROUND:

Oxidative stress and inflammation are involved in the pathophysiology of atherosclerosis. Our aim was to assess the effects of the antioxidant succinobucol (AGI-1067) on cardiovascular outcomes in patients with recent acute coronary syndromes already managed with conventional treatments.

METHODS:

After an acute coronary syndrome occurring 14-365 days before recruitment, 6144 patients were randomly assigned with a computer-generated randomisation list, stratified by study site, to receive succinobucol (n=3078) or placebo (n=3066) in addition to standard of care. Enrolment began in July, 2003; this event-driven trial was stopped in August, 2006, after the prespecified number of primary outcome events had occurred. The composite primary endpoint was time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, unstable angina, or coronary revascularisation. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00066898.

FINDINGS:

All randomised patients were included in the efficacy analyses. Succinobucol had no effect on the primary endpoint (530 events in succinobucol group vs 529 in placebo group; hazard ratio 1.00, 95% CI 0.89-1.13, p=0.96). The composite secondary endpoint of cardiovascular death, cardiac arrest, myocardial infarction, or stroke occurred in fewer patients in the succinobucol group than in the placebo group (207 vs 252 events; 0.81, 0.68-0.98, p=0.029). The tertiary endpoint of new-onset diabetes developed in fewer patients without diabetes at baseline in the succinobucol group than in such patients in the placebo group (30 of 1923 vs 82 of 1950 patients; 0.37, 0.24-0.56, p<0.0001). New-onset atrial fibrillation occurred more often in the succinobucol group than in the placebo group (107 of 2818 vs 55 of 2787 patients; 1.87, 1.67-2.09, p=0.0002). Although the number of patients who reported any treatment emergent adverse event was much the same in the two groups, more patients in the succinobucol group than in the placebo group reported bleeding episodes or anaemia (32 vs 18 and 37 vs ten, respectively) as serious adverse events. Relative to treatment with placebo, succinobucol increased LDL cholesterol and systolic blood pressure, and decreased HDL cholesterol and glycated haemoglobin (p<0.0001 for all).

INTERPRETATION:

Although succinobucol had no effect on the primary endpoint, changes in the rates of other clinical outcomes-both beneficial and harmful-will need to be further assessed before succinobucol is used in patients with atherosclerosis or as an antidiabetic agent.

Comment in

PMID:
18502300
[PubMed - indexed for MEDLINE]
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