Safety and efficacy of rivaroxaban for the secondary prevention following acute coronary syndromes among biomarker-positive patients: Insights from the ATLAS ACS 2-TIMI 51 trial.

Abstract

BACKGROUND::

Despite dual antiplatelet therapy, persistent thrombin generation and thrombin-mediated platelet activation account in part for the residual risk of atherothrombotic disease among patients with prior acute coronary syndrome (ACS). Inhibition of thrombin generation among high-risk ACS patients (biomarker-positive ACS) with the factor Xa inhibitor rivaroxaban may limit ongoing thrombus formation and myocardial necrosis and thereby improve clinical outcomes.

OBJECTIVES AND METHODS::

ATLAS ACS 2-TIMI 51 was a double-blind, placebo-controlled clinical trial that randomized ACS patients to either rivaroxaban 2.5 mg b.i.d., rivaroxaban 5 mg b.i.d., or placebo plus standard-of-care antiplatelet therapy for a mean of 13.1 months and up to 31 months ( N=15,526). This post-hoc analysis evaluates the safety and efficacy of rivaroxaban among biomarker-positive ACS patients with and without a history of prior stroke of transient ischemic attack in the ATLAS ACS 2-TIMI 51 trial.

RESULTS::

A total of 12,626 biomarker-positive ACS patients were included in this analysis. Among biomarker-positive patients without a prior history of stroke or transient ischemic attack, rivaroxaban 2.5 b.i.d. was associated with a reduction in the primary efficacy endpoint (composite of cardiovascular death, myocardial infarction, or stroke) as compared with placebo (hazard ratio=0.80, 95% confidence interval (0.68-0.94), p=0.007) at the expense of an increase in non-coronary-artery-bypass-graft-related Thrombolysis in Myocardial Infarction major bleeding (1.9% vs. 0.7%, p<0.0001), but not a significant increase in either intracranial hemorrhage (0.4% vs. 0.2%, p=0.11) or fatal bleeding (0.1% vs. 0.3%, p=0.16).

CONCLUSION::

Rivaroxaban 2.5 mg b.i.d. was associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, or stroke with no increase in fatal bleeding. Biomarker-positive patients with no prior history of stroke or transient ischemic attack may be a optimal target population to receive "dual pathway" therapy with rivaroxaban plus dual antiplatelet therapy for secondary prevention following ACS.

• Authors: Serge Korjian, Eugene Braunwald, Yazan Daaboul, Freek Verheugt, Christoph Bode, Michal Tendera, Purva Jain, Alexei Plotnikov, Paul Burton, C Michael Gibson
• Journal: European heart journal. Acute cardiovascular care (Eur Heart J Acute Cardiovasc Care) Vol. 8 Issue 2 Pg. 186-193 (Mar 2019) ISSN: 2048-8734 [Electronic] England
• PMID: 29249166 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Biomarkers
• Factor Xa Inhibitors
• Platelet Aggregation Inhibitors
• Troponin
• Rivaroxaban

Topics

• Acute Coronary Syndrome (complications)
• Administration, Oral
• Biomarkers (blood)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Factor Xa Inhibitors (administration & dosage)
• Follow-Up Studies
• Humans
• Platelet Aggregation Inhibitors (administration & dosage)
• Rivaroxaban (administration & dosage)
• Secondary Prevention (methods)
• Thrombolytic Therapy (methods)
• Thrombosis (blood, etiology, prevention & control)
• Time Factors
• Treatment Outcome
• Troponin (blood)