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J Am Coll Cardiol. 2019 May 21;73(19):2365-2383. doi: 10.1016/j.jacc.2019.02.015. Epub 2019 Mar 4.

Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction.

Author information

Duke Clinical Research Institute, Durham, North Carolina; Division of Cardiology, Duke University School of Medicine, Durham, North Carolina. Electronic address:
Ahmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, California. Electronic address:
Duke Clinical Research Institute, Durham, North Carolina; Division of Cardiology, Duke University School of Medicine, Durham, North Carolina.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts.
Nursing Institute and Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio.
Duke Clinical Research Institute, Durham, North Carolina.
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina.
Saint Luke's Mid America Heart Institute and the University of Missouri-Kansas City, Kansas City, Missouri.
Mended Hearts, Huntsville, Alabama.
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. Electronic address:



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.


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


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.


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.


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.


dose; heart failure; medication; reduced ejection fraction; registry


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