Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction

Abstract

Background: Guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown.

Objectives: This study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes.

Methods: Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up.

Results: At baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication.

Conclusions: In this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.

Keywords: dose; heart failure; medication; reduced ejection fraction; registry.

Figure 1.. Reasons for change in guideline-directed medical therapy over 12-month follow-up among patients with chronic HFrEF in contemporary US outpatient practice.

For each class of medication and for each type of medication change, reasons for medication change were classified as either patient decision/request, health team reason, medical reason, and systems-based reasons. Data regarding specific reasons within each category are provided in Supplementary Tables 6–9. ARB, angiotensin II receptor blocker; ACEI, angiotensin-converting enzyme inhibitor; ARNI, angiotensin receptor-neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist.

Central Illustration.. Changes in use and dose of guideline-directed medical therapy over 12-month follow-up among patients with chronic HFrEF in contemporary US outpatient practice.

Panel A: For each class of medication, data shown reflect the relative proportions of eligible patients by trajectory of medication use and dose from baseline to 12-month follow-up. Panel B: Sankey diagrams displaying detailed longitudinal trajectories of how patients moved between dosing groups over 3-month intervals of follow-up. ARB, angiotensin II receptor blocker; ACEI, angiotensin-converting enzyme inhibitor; ARNI, angiotensin receptor-neprilysin inhibitor; HFrEF, heart failure with reduced ejection fraction; MRA, mineralocorticoid receptor antagonist.