Log in to MyACC
Natriuretic Peptide Inclusion Criteria in COMMANDER HF Trial
Study Questions:
What is the effect of adding natriuretic peptide-based entry criteria on the clinical profile of patients enrolled, event rates, and study outcomes from the COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure) trial?
Methods:
COMMANDER HF was a double-blind, randomized trial comparing the factor Xa inhibitor rivaroxaban and placebo. Inclusion criteria included history of chronic heart failure (HF) for ≥3 months, treatment for decompensated HF in the previous 30 days, left ventricular ejection fraction (LVEF) ≤40%, history of coronary artery disease, and absence of atrial fibrillation or other indication for chronic anticoagulation. They defined decompensated HF as worsening dyspnea or fatigue with objective signs of congestion, and/or adjustment of HF medications, requiring hospital admission, or unscheduled parenteral diuretic. This study compared event rates and treatment outcomes of patients enrolled before and after the inclusion of plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP) level ≥800 ng/L or BNP level ≥200 ng/L at any time between the index admission for decompensated HF and randomization. The primary endpoint was all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints included HF rehospitalization and cardiovascular death.
Results:
A total of 5,022 patients with an LVEF ≤40% and coronary artery disease were included. Post-amendment patients were older (67 years vs. 65 years), with more diabetes (43% vs. 34%) and anemia (34% vs. 22%), higher heart rate (72 bpm vs. 69 bpm), and lower systolic blood pressure (122 mm Hg vs. 124 mm Hg) compared to patients enrolled pre-amendment. After the amendment, LVEF was lower (33% vs. 36%), estimated glomerular filtration rate was lower (67 ml/min/1.73 m2 vs. 71 ml/min/1.73 m2), and D-dimer was higher (380 μg/L vs. 310 μg/L) compared to pre-amendment. Clinical outcomes were affected as well. The primary efficacy endpoint was more common after the amendment. This was mostly driven by a higher rate of all-cause mortality. Risk of rehospitalization for HF increased after the amendment (20.74 vs. 11.82 events/100 patient-years, hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.49; p < 0.001). There was a trend towards increased rate of the primary safety endpoint (0.61 vs. 0.32 events/100 patient-years, HR, 1.51; 95% CI, 0.71-3.20; p = 0.28). Bleeding as defined by the International Society on Thrombosis and Hemostasis (ISTH) occurred more frequently in the post-amendment group.
Conclusions:
The amendment resulted in enrollment of patients with more comorbidities, 30% higher rates of the primary endpoint (death, MI, or stroke) driven by Eastern European sites, and higher rates of rehospitalization for HF, bleeding, and death (both cardiovascular and noncardiovascular). There was no difference in rivaroxaban treatment. Natriuretic peptide should be used as inclusion criteria in future HF trials.
Perspective:
The inclusion of natriuretic peptide should be considered as inclusion criteria for all trials assessing patient event rates in patients who have a history of HF hospitalizations.
Clinical Topics: Anticoagulation Management, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Anemia, Anticoagulants, Blood Pressure, Coronary Artery Disease, Diabetes Mellitus, Diuretics, Dyspnea, Factor Xa Inhibitors, Fatigue, Glomerular Filtration Rate, Heart Failure, Heart Rate, Hemostasis, Myocardial Infarction, Natriuretic Peptide, Brain, Natriuretic Peptides, Peptide Fragments, Stroke, Stroke Volume, Thrombosis, Treatment Outcome, Ventricular Function, Left
< Back to Listings
