A rationale for dedicated trials of combination therapy in heart failure.

As heart failure (HF) enters a new era with high level of evidence supporting the use of individual drug therapies, we put forth a rationale for the need for dedicated investigation of the safety, tolerability, and practicalities associated with combination medical therapy. Being able to tailor therapies via combination approaches might offer a way to maximize benefits of available therapies and also facilitate compliance. The evidentiary bar to support multi-drug regimens should be raised in HF for a variety of reasons: (1) Pivotal HF randomized controlled trials (RCTs) to date have not traditionally tested and proven safety and efficacy of drug combinations, (2) HF patients have variable disease trajectories, (3) There is hesitancy by clinicians and patients to using multiple drugs and such trials may build confidence in their use, and (4) HF therapies have overlapping side effects. Similar to combination therapies being developed and tested in adjacent fields of medicine, HF care too would greatly benefit from dedicated investigations of combination treatment approaches. Personalizing precision medicine with combination therapies has the potential to further improve outcomes and facilitate optimal implementation of disease-modifying therapies in HF.