Abstract
Multiple drug classes have shown incremental benefits in heart failure with reduced ejection fraction. Most of these trials were designed to achieve specific doses of the investigational agent. Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated. However, with the increasing number of available therapies, clinicians face the challenge of simultaneously using several drugs, achieving target doses, and managing side effects that are often overlapping. Blood pressure, renal function, hyperkalaemia, and other factors may impede achieving target doses of all medications, leaving clinicians with dilemmas as to how to sequence and dose these various classes of drugs. The guideline-directed eligibility for certain drugs and devices requires stability on maximally tolerated doses of background therapies. However, significant variability exists in dosing achieved in clinical practice. We discuss the existing background data regarding the doses of heart failure medications in clinical trials and in practice, and provide recommendations on how to navigate this complex therapeutic decision-making.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 286-296 |
| Number of pages | 11 |
| Journal | European Journal of Heart Failure |
| Volume | 21 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2019 |
Funding
lower doses are nevertheless associated with benefit. It is critical for clinicians to recognize the important contribution of each targeted pathway in the HF armamentarium and to maximize each of these therapies to the highest tolerated dose. Combining practical approaches with sound clinical judgment to optimize this important aspect of HF patient care is the key to improving outcomes for HF patient. Conflict of interest: C.N.M. reports consulting for Abbott and St. Jude Medical. G.C.F. reports research funding from NIH and consultant to Amgen, Janssen, Novartis, Medtronic, and St Jude Medical. S.D.A. reports research support from DZHK Germany, European Union, Vifor International & Abbott Vascular, and consultant to Astra-Zeneca, Bayer, Boehringer Ingelheim, CVRx, Janssen, Novartis, Servier and Vifor International. M.V. is supported by the NHLBI T32 postdoctoral training grant (T32HL007604). S.J.G. is supported by the NHLBI T32 postdoctoral training grant (5T32HL069749-14) and a Heart Failure Society of America/ Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis. J.L.J. report received grant support from Roche Diagnostics, Siemens, Singulex, Novartis, and Prevencio, and consulting for Roche Diagnostics, Critical Diagnostics, Abbott, Philips, and Novartis, and participates in clinical endpoint committees/data safety monitoring boards for Novar-tis, Amgen, Janssen, and Boehringer Ingelheim. M.G. reports being consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm SA, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical and Trevena Therapeutics. G.F. reports consults to Bayer, Boehringer Ingelheim, Novartis, and Servier. J.B. reports research support from the NIH, European Union, and Patient Centered Outcomes Research Institute, and consultant to Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, BMS, CVRx, Janssen, Luitpold, Medtronic, Novartis, Relypsa, Vifor, ZS Pharma. The other authors report no disclosures.
Keywords
- Doses
- Heart failure
- Medications
- Outcomes
- Reduced ejection fraction
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
