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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.

Publication ,  Journal Article
Steg, PG; Mehta, SR; Jukema, JW; Lip, GYH; Gibson, CM; Kovar, F; Kala, P; Garcia-Hernandez, A; Renfurm, RW; Granger, CB; RUBY-1 Investigators,
Published in: Eur Heart J
October 2011

AIMS: 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). METHODS: 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. RESULTS: Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95% CI: 1.13-4.60, P = 0.022). Using placebo as reference (bleeding rate 3.1%), there was a dose-response 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. CONCLUSIONS: 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. ClinicalTrials.gov Identifier: NCT00994292.

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Published In

Eur Heart J

DOI

EISSN

1522-9645

Publication Date

October 2011

Volume

32

Issue

20

Start / End Page

2541 / 2554

Location

England

Related Subject Headings

  • Treatment Outcome
  • Thromboembolism
  • Stroke
  • Secondary Prevention
  • Risk Factors
  • Myocardial Ischemia
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
 

Citation

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Steg, P. G., Mehta, S. R., Jukema, J. W., Lip, G. Y. H., Gibson, C. M., Kovar, F., … RUBY-1 Investigators, . (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. Eur Heart J, 32(20), 2541–2554. https://doi.org/10.1093/eurheartj/ehr334
Steg, Ph Gabriel, Shamir R. Mehta, J Wouter Jukema, Gregory Y. H. Lip, C Michael Gibson, Frantisek Kovar, Petr Kala, et al. “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.Eur Heart J 32, no. 20 (October 2011): 2541–54. https://doi.org/10.1093/eurheartj/ehr334.
Steg, Ph Gabriel, et al. “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.Eur Heart J, vol. 32, no. 20, Oct. 2011, pp. 2541–54. Pubmed, doi:10.1093/eurheartj/ehr334.
Steg PG, Mehta SR, Jukema JW, Lip GYH, Gibson CM, Kovar F, Kala P, Garcia-Hernandez A, Renfurm RW, Granger CB, RUBY-1 Investigators. 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. Eur Heart J. 2011 Oct;32(20):2541–2554.
Journal cover image

Published In

Eur Heart J

DOI

EISSN

1522-9645

Publication Date

October 2011

Volume

32

Issue

20

Start / End Page

2541 / 2554

Location

England

Related Subject Headings

  • Treatment Outcome
  • Thromboembolism
  • Stroke
  • Secondary Prevention
  • Risk Factors
  • Myocardial Ischemia
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate