Results of a multi-center, randomized clinical trial which enrolled 894 patients with heart failure (HF) with reduced ejection fraction (EF ≤40%) published in the most recent issue of the Journal of the American College of Cardiology (JACC) have shown that management, using NT-ProBNP-guided optimal medical therapy, has higher total costs and fails to show superior efficacy in improving quality of life (QoL) outcomes compared to usual care (titration of guideline-recommended therapy to doses established in pivotal clinical trials).
The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial planned to prospectively enroll 1100 patients from 45 clinical sites in the United States and Canada. After a scheduled review by the DSMB, the study was stopped for lack of efficacy of the biomarker-guided strategy. The patients included in the study presented with chronic HF and an EF of ≤40%; these subjects were randomly assigned in a 1:1 fashion to an NT-proBNP-guided treatment strategy (n=446) or usual care (n=448). Patients in the NT-proBNP- guided strategy received medical therapy with a goal of achieving a NT-proBNP level <1000 pg/ml. Structured evaluations performed at baseline and 3, 6, 12, and 24 months post-randomization were employed to collect and compare data on quality of life (QoL). The Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI) were used to stratify pre-specified QoL measures. In addition, researchers examined the costs associated with either treatment strategy in 735 US patients. The results showed that both the KCCQ and the DASI improved over the first 6 months ( 11-point improvement in the 4 KCCQ composite scales which included physical limitations, total symptoms, QoL, and social limitations), but no evidence was found for a strategy-related difference (mean difference [biomarker-guided usual care] at 24 months of follow-up, 2.0 for DASI [95% confidence interval (CI): 1.3 to 5.3] and 1.1 for KCCQ [95% CI: 3.7 to 5.9]). Albeit the lack of strategy-related difference, both treatment arms did show improvements in KCCQ and DASI scores overall. Total winsorized costs (to reduce the effect of possibly false outliers) averaged $5,919 higher in the biomarker-guided strategy (95% CI: $1,795 + $13,602) over 15-month median follow-up.
“The big message from GUIDE-IT, or a big message from GUIDE-IT, is that, regardless of which arm you ran patients on or who got treated more aggressively, when we were able to get their NT-proBNP levels down, the lower did better regardless of which treatment arm they were in.” – G. Michael Felker, MD, MHS (Duke University Medical Center)
Previous trials have revealed various effective management strategies for HF patients that lead to symptomatic relief (primarily dyspnea) and improve prognosis but other major symptoms such as fatigue and exercise intolerance have not been well correlated with either central measures of cardiac performance or measures of patient-reported QoL. Indeed, most of the clinical trials of effective medical therapies in HF that included QoL measurement showed small or no changes in QoL. NT‐proBNP has emerged as a powerful biomarker in various cardiovascular diseases and serves to provide strong and independent prognostic information in patients with heart failure. The investigators of the GUIDE-IT trial aimed to study whether the attempt to achieve a sufficiently low NT-proBNP level would affect QoL either beneficially or adversely. The investigators concluded that they found no evidence of a QoL effect associated with randomization to the strategy of NT-proBNP– guided therapy. In 735 patients enrolled in the United States, medical costs were increased in the biomarker-guided arm, primarily due to extra hospital-based care.
The limitations of the study included early termination with less follow-up time than was planned for in the trial design, secondly the unblinded nature of the analyses may have contributed to the lack of benefit seen in the biomarker-guided arm. Thirdly, both groups had more frequent medical contacts related to study participation compared to standard of care.