Debra L. Beck and Eugene Braunwald, MD
The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial was designed to prospectively study the relationship between change in natriuretic peptide concentration, cardiac remodeling, and clinical events in patients with heart failure with reduced ejection fraction (HFrEF). The trial was stopped early because biomarker-guided treatment was not more effective than usual care in improving outcomes. The GUIDE-IT Echo Substudy was a prespecified substudy designed to understand the influence of biomarker-guided therapy on cardiac structure and function.
From the larger trial, 124 patients with HFrEF (EF ≤40%) randomly assigned to either pro-B-type natriuretic peptide (NT-proBNP)-guided treatment or usual care had paired echocardiograms performed at baseline and 12 months. Remodeling indices and clinical outcomes were compared between treatment arms and by achievement of the NT-proBNP goal of <1,000 pg/ml at 12 months.
At 12 months, as seen in the main analysis of the 894-patient strong GUIDE-IT trial, the changes in EF and LV volumes were similar between the biomarker-guided and usual care arms with no difference in clinical outcomes.
However, when the researchers pooled patients who did and did not achieve a lowering of NT-proBNP to <1,000 pg/ml, regardless of treatment strategy, reaching the NT-proBNP goal was associated with a significantly greater absolute increase in EF compared with those not reaching goal (9.9% vs. 2.9%; p < 0.001). As well, LV indexed end-diastolic and end-systolic volumes were significantly more reduced in those achieving NT-proBNP goal. Adverse events were also significantly lower among patients achieving the NT-proBNP goal (p < 0.001).
The extent of reverse remodeling correlated with the change in NT-proBNP: a decrease of 1,000 pg/ml was associated with an increase in EF of 6.7% and greater reductions in LV volumes.
Patients with nonischemic cardiomyopathy were more likely to achieve a NT-proBNP goal <1000 pg/ml at 1 year than patients with ischemic cardiomyopathy.
The researchers concluded that among patients with HFrEF, lowering NT-proBNP to <1,000 pg/ml by 12 months was associated with significant reverse remodeling and improved outcomes, regardless of the treatment strategy employed. Their findings “suggest that perhaps it is not the treatment strategy, but the response to treatment as assessed by change in NT-proBNP that is important,” wrote the authors.
Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine features a unique update program by Dr. Braunwald, creating a “living textbook” by featuring weekly Hot off the Press, periodic Late-Breaking Clinical Trials (including links to authors’ presentation slides), and monthly Focused Reviews.
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