Centralized Protocol Improves Optimization of Guideline-Concordant Medical Therapy for HFrEF Patients Hospitalized for Any Reason

Doctor on laptop with stethoscope on table, electronic health record concept

AHA/ACC/HFSA guidelines recommend rapid multidrug regimen implementation for patients with heart failure with reduced ejection fraction (HFrEF). However, even though patients with HFrEF face a considerable risk of disease progression and mortality, optimal regimens and doses are rarely achieved.

Researchers at Brigham and Women’s Hospital previously found hospitalization for any reason is a significant opportunity to optimize care for HFrEF. In an initial single-center pilot study, IMPLEMENT-HF, a centralized virtual team made protocolized, virtual suggestions to treating clinicians for patients hospitalized for any reason, and not necessarily heart failure, if the patients had a history of HFrEF. The pilot suggested that the centralized virtual approach improved the use of guideline-concordant medical therapy.

In the Journal of the American College of Cardiology, the team reports similar results from the full implementation of IMPLEMENT-HF across three centers. The authors are Muthiah Vaduganathan, MD, MPH, a cardiologist in the Division of Cardiovascular Medicine, Ankeet S. Bhatt, MD, MBA, ScM, formerly a fellow in the Division, Danielle M. Knowles, PharmD, a pharmacist, Dale S. Adler, MD, a cardiologist and executive vice chair of the Department of Medicine, and many other colleagues.


The full trial enrolled 198 adults with previously or newly diagnosed HFrEF admitted to the Brigham or Brigham and Women’s Faulkner Hospital or Salem Hospital for any reason between October 2021 and June 2022. 66% of participants were male, the mean age was 69, 73% were white, 14% were Black, 17% were Latino/a/x, and 12% were predominantly Spanish-speaking.

Overall, 107 encounters (occurring in 83 patients) were compared to 145 encounters (occurring in 115 patients).

The intervention involved having a virtual team review each patient’s electronic health record and give suggestions to treating clinicians up to once daily according to an evidence-based algorithm. The algorithm, published in the article’s supplemental materials, prioritized establishing multidrug class therapy before dose up-titration, even at low doses.

The team consisted of a centralized physician, study staff, and pharmacist. Important parts of the team were based at each of the participating hospitals. Team members had no direct contact with patients.

The primary outcome was the composite score for in-hospital guideline-concordant changes in HFrEF medical therapy, defined as the sum of optimization changes (+2 point for drug initiations, +1 for dose up-titrations) and deoptimization changes (−2 point for drug discontinuations, −1 for dose down-titrations).

Primary Outcome

The virtual team made 187 recommendations to clinicians caring for patients in the intervention arm. The mean composite score was 1.1 in the intervention group vs. 0.4 with usual care (adjusted β, +1.2; P<0.001).

Change in Specific Therapies

Across all drug classes included in the algorithm, the proportion of patients newly started on therapy during hospitalization was higher in the intervention arm than the usual care arm:

  • Beta-blockers—81% vs. 44% (P=0.005)
  • Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers—17% vs. 15%
  • Angiotensin receptor–neprilysin inhibitors—8% vs. 5%
  • Mineralocorticoid receptor antagonists—32% vs. 11% (P=0.001)
  • Sodium-glucose cotransporter-2 inhibitors—14% vs. 9%

Net Optimization

The intervention led to a 20% absolute improvement in net in-hospital optimization. Specifically, 44% of patients in the intervention arm vs. 24% in usual care had a composite score >0 (P=0.002). The number needed to intervene was five clinical encounters for one net optimization.

Other Findings

Benefits on the primary endpoint were consistent by age, sex, and race; whether the patient had newly diagnosed or established HFrEF; and whether the encounters were primarily for acute HF or other admission reasons. For unclear reasons, the intervention was less effective among encounters involving Latino/a/x patients and predominantly Spanish-speaking patients.

The intervention was not associated with a significant increase in any adjudicated serious adverse event. The length of stay was similar in the two groups.

The Path Forward

The intervention evaluated in this study is readily scalable. In-hospital management guided by a centralized virtual team could be the initial step in safely establishing multicomponent, guideline-concordant drug therapy for HFrEF.

Pairing the in-hospital strategy with efficient interventions in the transitional and early outpatient periods might accelerate the initiation of additional drug classes, encourage dose optimization, and promote treatment persistence.

Specifically relevant to the Mass General Brigham system was the education that the study provided to the community hospitals, and the remarkable cooperation and effort that the community hospitals provided, thus laying the foundation for other cooperative quality improvement efforts across the health system.

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