Pharmacist-Assisted Titration of Rx to Implement Optimal Medical Therapy for Heart Failure

Heart failure with reduced ejection fraction (HFrEF) affects a large proportion of Veterans and isa leading cause of hospitalization and death. Clinical guidelines recommend four classes of medications (commonly called "quadruple therapy") that improve survival and reduce hospitalizations, yet 42% of Veterans hospitalized with heart failure do not receive all recommended medications at discharge.

This study implements a virtual pharmacist and cardiologist team (hub) that provides digital consultation to hospitalists and primary care providers (spoke) at VA medical centers regarding use of guideline-directed medical therapy (GDMT) during hospitalization and the post-discharge period. The pharmacist/cardiologist team identifies eligible Veterans using a VA hospital-specific dashboard, reviews electronic health records, and places digital consultation notes with individualized medication recommendations, safety surveillance information, and out-of-pocket medication cost data.

The intervention also incorporates identification of Veterans hospitalized in VA-paid community care settings. Veterans hospitalized with heart failure in community hospitals within the preceding 3 months are identified via VA-paid community care claims data, and actionable recommendations are provided through the VA electronic health record or by facsimile to community providers.

Six VA medical centers served by Clinical Resource Hubs in VISNs 4, 16, 17, 19, and 23 are participating. Sites are randomized to one of three implementation waves in a cluster-randomized stepped-wedge design, with implementation occurring every 6 months at two sites per wave. This design allows estimation of intervention effects using both within- and between-site comparisons while controlling for secular trends. A difference-in-differences analytic approach with covariate-constrained randomization is used to estimate causal effects.

The primary effectiveness outcome is change in GDMT optimization score from admission to 14 days after discharge. Secondary effectiveness/safety outcomes include mortality, heart failure readmission, and medication-related adverse events at 90 days. Implementation outcomes are assessed using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework and include fidelity to identification of at-risk Veterans, provision of recommendations,, outpatient follow-up rates, and barriers and facilitators to implementation Additional outcomes derived from the RE-AIM framework will also be captured.

• Pharmacist/Cardiologist Virtual Team Digital Consultation (Behavioral), also known as PATRIOT-HF intervention; pharmacist-assisted GDMT optimization: A centralized pharmacist and cardiologist virtual team (hub) provides protocol-based digital consultation notes to inpatient and outpatient providers(spoke) regarding initiation and intensification of guideline-directed medical therapy (GDMT) for heart failure during hospitalization and the post-discharge transitional care period. Eligible Veterans are identified via VA dashboards and community care claims data. Recommendations cover quadruple therapy (beta blockers, ACEI/ARB/ARNI, MRA, SGLT2i) and are tailored to individual clinical presentations. The pharmacist arranges outpatient follow-up and delivers medication adherence education.

Primary outcomes

• Change in Guideline-Directed Medical Therapy (GDMT) Optimization Score [From hospital admission (baseline) to 14 days after discharge (VA direct care) or 14 days after Veteran eligibility identification (VA community care)]: The GDMT Optimization Score reflects the proportion of eligible guideline-recommended heart failure medications prescribed relative to the total for which the Veteran is eligible. Points are assigned as follows - Numerator: ACEI/ARB=1, ARNI=2, evidence-based beta blocker=2, MRA=2, SGLT2i=2, Vericiguat=1, Ivabradine=1, Hydralazine/Nitrates=1. Denominator reflects eligibility for each class. A higher score indicates greater concordance with guidelines.

Secondary outcomes

• Change in NIH Heart Failure Collaboratory Score [From hospital admission (baseline) to 14 days after discharge (VA direct care) or Veteran eligibility identification (VA community care)]: A composite GDMT metric assessing the breadth and completeness of guideline-recommended heart failure pharmacotherapy.
• All-cause mortality [30 days and 90 days after hospital discharge (VA direct care) or Veteran eligibility identification (VA community care)]: Death from any cause, ascertained from the VA Death Ascertainment File.
• Heart Failure Readmission [30 days and 90 days after hospital discharge (VA direct care) or Veteran eligibility identification (VA community care)]: A claim for inpatient admission with any HF diagnosis on the claim, ascertained from the VA Corporate Data Warehouse and Consolidated Data Set.
• Medication-related adverse outcomes - acute kidney injury [90 days after hospital discharge or Veteran eligibility identification]: Acute kidney injury identified by creatinine levels and ICD diagnostic codes in the VA Corporate Data Warehouse.
• Medication-related adverse outcomes - bradycardia [90 after hospital discharge or Veteran eligibility identification]: Bradycardia identified by vital sign readings and ICD diagnostic codes in the VA Corporate Data Warehouse.
• Medication-related adverse outcomes - hyperkalemia [90 days after hospital discharge or Veteran eligibility identification]: Hyperkalemia identified by potassium laboratory values and ICD diagnostic codes in the VA Corporate Data Warehouse.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Admission to a VA medical center or VA-paid community hospital within the preceding 3 months with a primary diagnosis of heart failure

  * The primary study cohort will consist of those admitted to a VA medical center, while the secondary study cohort will consist of patients admitted to VA-paid community hospitals
* Left ventricular ejection fraction ≤ 40%
* Not on optimal guideline-directed heart failure medication classes or doses, as assessed in the electronic health record
* Receiving care within one of the 6 participating VA medical centers

Exclusion Criteria:

* Hemodynamic instability
* Receiving comfort care measures alone or enrolled in hospice

• Paul L Hess, MD MS, Principal investigator, Rocky Mountain Regional VA Medical Center, Aurora, CO