RUBY-1: a randomized, double-blind, placebo-controlled trial of
the safety and tolerability of the novel oral factor Xa
inhibitor darexaban (YM150) following acute coronary syndrome

J 2011

RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

STEG, Ph. Gabriel; Shamir R. MEHTA; J. Wouter JUKEMA; Gregory Y. H. LIP; C. Michael GIBSON et al.

Základní údaje

Originální název

RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

Autoři

STEG, Ph. Gabriel; Shamir R. MEHTA; J. Wouter JUKEMA; Gregory Y. H. LIP; C. Michael GIBSON; František KOVAR; Petr KALA; Alberto GARCIA-HERNANDEZ; Ronny W. RENFURM a Christopher B. GRANGER

Vydání

European Heart Journal, 2011, 0195-668X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 10.478

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/11:00054051

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1093/eurheartj/ehr334

UT WoS

000295939400022

Klíčová slova anglicky

Anticoagulant; Acute coronary syndrome; Secondary prevention; Darexaban

Příznaky

Mezinárodní význam

Změněno: 25. 11. 2011 13:51, Mgr. Michal Petr

Anotace

V originále

To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS). In a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia. Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95 CI: 1.134.60, P 0.022). Using placebo as reference (bleeding rate 3.1), there was a doseresponse relationship (P 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3 for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity. Darexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial.

Citovat

STEG, Ph. Gabriel; Shamir R. MEHTA; J. Wouter JUKEMA; Gregory Y. H. LIP; C. Michael GIBSON; František KOVAR; Petr KALA; Alberto GARCIA-HERNANDEZ; Ronny W. RENFURM a Christopher B. GRANGER. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. European Heart Journal. 2011, roč. 32, č. 20, s. 2541-2554. ISSN 0195-668X. Dostupné z: https://doi.org/10.1093/eurheartj/ehr334.

@article{959103,
   author = {Steg, Ph. Gabriel and Mehta, Shamir R. and Jukema, J. Wouter and Lip, Gregory Y. H. and Gibson, C. Michael and Kovar, František and Kala, Petr and GarciaandHernandez, Alberto and Renfurm, Ronny W. and Granger, Christopher B.},
   article_number = {20},
   doi = {https://doi.org/10.1093/eurheartj/ehr334},
   keywords = {Anticoagulant; Acute coronary syndrome; Secondary prevention; Darexaban},
   language = {eng},
   issn = {0195-668X},
   journal = {European Heart Journal},
   note = {RUBY-1 Investigators},
   title = {RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome},
   volume = {32},
   year = {2011}
}

TY  - JOUR
ID  - 959103
AU  - Steg, Ph. Gabriel - Mehta, Shamir R. - Jukema, J. Wouter - Lip, Gregory Y. H. - Gibson, C. Michael - Kovar, František - Kala, Petr - Garcia-Hernandez, Alberto - Renfurm, Ronny W. - Granger, Christopher B.
PY  - 2011
TI  - RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome
JF  - European Heart Journal
VL  - 32
IS  - 20
SP  - 2541-2554
EP  - 2541-2554
SN  - 0195668X
N1  - RUBY-1 Investigators
KW  - Anticoagulant
KW  - Acute coronary syndrome
KW  - Secondary prevention
KW  - Darexaban
N2  - To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS). In a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia. Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95 CI: 1.134.60, P 0.022). Using placebo as reference (bleeding rate 3.1), there was a doseresponse relationship (P 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3 for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity. Darexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial.
ER  -

STEG, Ph. Gabriel; Shamir R. MEHTA; J. Wouter JUKEMA; Gregory Y. H. LIP; C. Michael GIBSON; František KOVAR; Petr KALA; Alberto GARCIA-HERNANDEZ; Ronny W. RENFURM a Christopher B. GRANGER. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. \textit{European Heart Journal}. 2011, roč.~32, č.~20, s.~2541-2554. ISSN~0195-668X. Dostupné z: https://doi.org/10.1093/eurheartj/ehr334.

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