Abstract
ObjectiveTo evaluate effects of atrial fibrillation (AF) on cardiac biomarkers and outcomes in a trial population of patients with heart failure (HF) with reduced ejection fraction treated with optimal guideline-directed medical therapy.MethodsWe performed a secondary analysis of 894 patients in the Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial (January 2013–July 2016). Patients were stratified by AF status and compared with regard to guideline-directed medical therapy use, longitudinal levels of N-terminal pro–B type natriuretic peptide (NT-proBNP), and outcomes including HF hospitalization and mortality.ResultsAfter adjustment, AF was associated with a significant increase in the risk of HF hospitalization or cardiovascular death (hazard ratio, 1.28; 95% CI, 1.02 to 1.61; P=0.04) and HF hospitalization (hazard ratio, 1.31; 95% CI, 1.02 to 1.68; P=.03) but with no difference in mortality during a median 15 months of follow-up. There were no significant differences in medication treatment between those with and those without AF. At 90 days, a higher proportion of patients with AF (89.4% vs 81.5%; P=.002) had an NT-proBNP level above 1000 pg/mL (to convert NT-proBNP values to pmol/L, multiply by 0.1182), and AF patients had higher NT-proBNP levels at all time points through 2 years of follow-up.ConclusionAmong patients with HF with reduced ejection fraction, prevalent AF was associated with higher NT-proBNP concentrations through 2 years of follow-up and higher risk for HF hospitalization despite no substantial differences in medical therapy.
Highlights
The goal of our study was to evaluate differences in NT-proBNP levels and outcomes among patients with HF with reduced ejection fraction (HFrEF) with and without atrial fibrillation (AF) who were enrolled in the GUIDE-IT trial, an randomized controlled trial (RCT) designed to evaluate the efficacy of an NT-proBNPeguided heart failure (HF) treatment strategy
Whereas prior studies have reported that AF worsens outcomes in a communitybased observational cohort of patients with HFrEF with variable management,[7] this study found that this effect persists even in this contemporary trial cohort observed closely with frequent study-related clinic visits and having protocol-driven optimization of HF therapies.[1]
We found that among those with HFrEF, AF was associated with an increased risk of HF hospitalization or CV death and an increased risk of HF hospitalization alone; when stratified by NT-proBNP level of 1000 pg/mL, these findings persisted only among those with AF and NT-proBNP level of 1000 pg/mL and higher
Summary
This study uses the data from the GUIDE-IT trial, the results of which have previously been published.[1] This trial was a randomized multicenter clinical trial conducted at 45 clinical sites in the United States and Canada. Patients were randomized to either an NT-proBNPeguided strategy or usual care. Those randomized to the guided strategy had GDMT titrated to achieve GDMT targets when possible but with a parallel goal of achieving a target NT-proBNP concentration of less than 1000 pg/mL. Patients randomized to the usual care arm were managed as recommended in HF clinical practice guidelines.[1,13] The primary end points were time to first HF hospitalization or CV death, and the trial was stopped because of futility after 894 of the planned 1100 patients had been enrolled. The Yale University Institutional Review Board approved requisition of the data, and waiver of consent was provided to conduct this study
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