Factor Xa inhibitor reduces stroke risk in patients with HFrEF, sinus rhythm and CAD

Rivaroxaban and stroke events in patients with heart failure, sinus rhythm, and coronary disease: the COMMANDER-HF trial

News - May 25, 2019

Introduction and methods

The COMMANDER-HF trial demonstrated that rivaroxaban gave no benefit compared to placebo for the primary outcome of all-cause mortality, MI, or stroke in patients with HF, sinus rhythm and coronary disease. Stroke was a component of the primary endpoint and was not studied as an individual outcome.

The COMMANDER-HF (Sept 2013-Oct 2017) enrolled patients with an episode of worsening HFrEF, within 21 days of the index event, with elevated BNP or NT-proBNP, CAD and sinus rhythm. At discharge, patients were randomized to receive rivaroxaban 2.5 mg bid (n=2507) or placebo (n=2515) and were followed for a median of 21 months.

The objective of this analysis was to examine the incidence, timing, type, severity and predictors of a stroke or TIA in patients after a recent episode of worsening chronic HFrEF, coronary artery disease (CAD) and sinus rhythm. Also, net clinical benefit of treatment with low dose rivaroxaban vs. placebo was assessed in these patients.

Main results

  • There were 150 first neurological events (127 stroke and 23 TIA). Using Modified Ranking Scale, 51% had non-disabling stroke, 17% had disabling stroke and 31% had fatal stroke.
  • Among survivors, 21% of patients were hospitalized for HF, 7% had stroke/TIA and 26% died.
  • In the placebo arm, timing of stroke/TIA after episode of worsening HF peaked at 2-3 months after the episode, but cumulative risk increased steadily over time.
  • Main predictors of stroke were region and history of stroke.
  • Rivaroxaban reduced the risk of time to first occurrence of stroke or TIA compared to placebo (adjHR 0.69, 95%CI: 0.50-0.95).
  • Risk of ischemic stroke was reduced with rivaroxaban vs. placebo (HR 0.64, 95%CI: 0.43-0.95, P=0.028), but risk for TIA or hemorrhagic stroke were not significantly different between groups.
  • In the overall cohort, NNT was 164 per year to prevent all-cause stroke or TIA, which was reduced to 96 per year when stratifying for CHA₂DS₂VASc >4.
  • Safety endpoint of fatal bleeding or bleeding into a critical space was not different between groups, nor after stratifying for CHA₂DS₂VASc.


In a subanalysis of the COMMANDER-HF trial, patients with HFrEF, CAD and sinus rhythm had a stroke/TIA risk approaching that observed in patients with chronic HF and AF. Risk of stroke/TIA peaked at 2-3 months, but persisted. Almost half of all strokes were disabling or fatal stokes. Rivaroxaban treatment resulted in reduced risk of first stroke by 31% without an increase in major bleeding. In those with CHA₂DS₂VASc >4 rivaroxaban vs. placebo seemed to give greater benefit compared to the overall population.


The discussant John McMurray found this an interesting analysis and important, as it is devasting for patients to have HF and suffer from stroke, especially when it is disabling. He raised the point that we do not understand the pathophysiology of HF and sinus rhythm resulting in increased stroke risk. Is it because of poor systolic function? Studies have not demonstrated an association between EF and stroke and stroke risks seem to be similar in HFpEF and HFrEF. Is it perhaps due to AF? McMurray noted that the event rate of stroke and TIA in this study was quite high. He wondered why that was. Was this a high-risk population? Or was it because events weren’t adjudicated? In addition, he noted that the risk-benefit balance was more favorable than in other studies with anticoagulants. Perhaps a conservative criterion of bleeding was used in this study.

Our reporting is based on the information provided at the ESC Heart Failure 2019 congress

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