Optimal Medical Therapy in Heart Failure: Reasons for Lack of Medication Titration in the GUIDE IT Trial

Background The use of guideline directed medical therapy (GDMT) improves clinical outcomes in patients with heart failure (HF). Despite this, many patients are under-treated. This led to the hypothesis that serial measurements of natriuretic peptides may be useful to guide titration of medical therapy, and achieve better outcomes (the GUIDE-IT trial). We evaluated the reported reason for not following the protocol and increasing GDMT medications. Methods GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) explored a ‘guided’ therapy with a goal to suppress NT-proBNP ≤1000 pg/mL on clinical outcomes of HF with reduced Ejection Fraction (HFrEF), utilizing a protocol of suggested medication titrations. For each clinical encounter, medication titrations were captured, along with a reason if a modification was not made. 894 patients were randomized to either the biomarker guided or GDMT group. Reasons were provided by the site in categorical and free-text reasons, and mapped to appropriate groupings. There were no differences between groups in rates and % of target doses achieved, but only about half achieved target doses of B-Blockers and ACE-I/ARB, and only half were on an MRA by end of study. Results This analysis included 6223 visits over a maximum of 24 months. In total, medication adjustments were made in 51% of the study visits representing 831(94%) of patients. The majority (74%) of adjustments occurred within the first 6 months, primarily within the first 6 weeks of enrollment (52%). Reasons for not titrating medications are shown in Figure 1. The primary reason for not adjusting medication was clinician decision, with the second top reason listed as already at maximally tolerated therapy. Conclusions Despite a protocol-driven approach to titrating HF medications, many patients did not receive GDMT medication adjustments in GUIDE IT, particularly in the long term. There may be a gap in opportunities to titrate medications for maximal benefit in HF.