This article is more than 5 years old. Information may no longer be current.
COMMANDER HF: Low-dose rivaroxaban not effective in HF with sinus rhythm and CAD
Click Here to Manage Email Alerts
MUNICH — Low-dose rivaroxaban, when added to guideline-based therapy, did not improve all-cause mortality, MI or stroke, nor did it favorably influence HF hospitalization compared with placebo among patients with chronic HF, reduced ejection fraction and CAD in the COMMANDER HF study.
Among 5,022 patients randomly assigned to treatment with twice-daily rivaroxaban 2.5 mg or placebo, the rate of the primary efficacy outcome — all-cause mortality, MI or stroke — occurred in 25% of the rivaroxaban (Xarelto, Janssen) group vs. 26.2% of the placebo group over a median-follow-up of 21 months (HR = 0.94; 95% CI, 0.84-1.05), Faiez Zannad, MD, PhD, from Université de Lorraine and Centre Hospitalier Régional Universitaire, Nancy, France, reported at the European Society of Cardiology Congress.
The principal safety outcome — fatal bleeding or bleeding occurring in a critical space with potential of permanent disability — occurred in 0.7% of the rivaroxaban group vs. 0.9% of the placebo group (HR = 0.8; 95% CI, 0.43-1.45). While fatal bleeding was similar with both treatments, those assigned rivaroxaban had fewer critical-space bleeding events. The researchers also evaluated ISTH-defined major bleeding and found greater risk among those treated with rivaroxaban (3.3% vs. 2%; HR = 1.68; 95% CI, 1.18-2.39).
The randomized, double-blind COMMANDER HF study was conducted at 628 sites in 32 countries. Patients enrolled had chronic HF, left ventricular ejection fraction of 40% or less, CAD and elevated plasma concentrations of natriuretic peptides, but no atrial fibrillation. All patients were enrolled within 21 days of an episode of worsening HF. The mean age at baseline was 66 years, one-quarter were women and most were white.
The trial tested rivaroxaban vs. placebo on top of guideline-recommended care for HF and CAD. Zannad noted that this patient population was “remarkably well treated.” At baseline, nearly all patients (99.5%) were taking diuretics, 93% ACE inhibitors or angiotensin receptor blockers, 92% beta-blockers and 76% mineralocorticoid receptor antagonists. Ninety-three percent of patients were taking aspirin, either alone or in combination with a thienopyridine, and 35% were on dual antiplatelet therapy at the start of the trial.
While the primary efficacy outcome was neutral between the two groups, the researchers analyzed individual components of the composite outcome and found that stroke was significantly less frequent in the rivaroxaban group (2% vs. 3%; HR = 0.66; 95% CI, 0.47-0.95). MI was also less frequent in the rivaroxaban group, but this finding did not reach statistical significance (3.9% vs. 4.7%; HR = 0.83; 85% CI, 0.63-1.08), Zannad said.
In other results, a secondary composite outcome of CV mortality plus HF hospitalization was not modified by rixaroxaban treatment (37.2% vs. 36.9%; HR = 0.99; 95% CI, 0.91-1.09), Zannad said. Additionally, treatment had no effect on venous thromboembolism or pulmonary embolism in this patient population, he said.
Serious adverse events that occurred during follow-up were similar, at 15.2% in the rivaroxaban group vs. 14.3% in the placebo group, according to the findings.
Discussing the results at ESC Congress, Zannad noted that a potential reason underlying why low-dose rivaroxaban failed to improve CV outcomes in COMMANDER HF may be that “in this specific population, HF, rather than deaths mediated by atherothrombotic events, contributed to a substantial proportion of all deaths.” The researchers discussed in the simultaneous publication in The New England Journal of Medicine that “whether a higher dose of rivaroxaban could have led to a more favorable outcome remains unknown.”
“The main conclusion [is] that now we should not conduct anticoagulation trials in this population because the HF events are not influenced by antithrombotic agents and thrombosis doesn’t much influence HF outcomes in itself,” Zannad said here. – by Katie Kalvaitis
References:
Zannad F. Hot Line Session 3. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.
Zannad F, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1808848.
Disclosures: The trial was sponsored by Janssen Research and Development. Zannad reports financial ties with Bayer and Janssen. Please see the full study for a list of the other authors’ relevant financial disclosures.
Perspective
Back to Top
Mary Norine Walsh, MD, MACC
These results were not surprising, because other trials of anticoagulation strategies in patients with HF and low EF have not demonstrated benefit. However, I think this is an important trial that adds to what we knew before. It used to be a common clinical practice to anticoagulate patients with very low EF in the absence of AF or another indication for anticoagulation. The practice then was to put patients on low-dose warfarin. That practice has largely stopped, and this study reinforces that we need more hard evidence before we anticoagulate these patients. We should not anticoagulate patients with HF with reduced EF in the absence of AF, atrial flutter, deep vein thrombosis, a mechanical heart valve or another anticoagulation indication.
St. Vincent Heart Center, Indianapolis
Click Here to Manage Email Alerts