Title: Early simultaneous versus stepwise implementation of Guideline-directed medical therapy in Veterans with reduced ejection fraction heart failure at the Washington DC VA Medical Center: Impact on clinical outcomes and tolerability.
Authors: Dr. LaNisha Potts, PharmD
Dr. Bi Kim, PharmD, BCPS, BCCCP
Dr. Josephine Tefferi, PharmD, MPH,BCPS, BCGP
Dr. Samuel Oh, PharmD, BCPS
Learning Objectives:
1. Determine whether early simultaneous implementation of GDMT results in lower rates of hospitalization for HF exacerbation compared to stepwise implementation.
2. Evaluate the impact of simultaneous versus stepwise GDMT implementation on cardiovascular mortality in Veterans with reduced ejection fraction heart failure (HFrEF, EF<40%).
Objective:
The primary objective of this study is to compare the clinical outcomes of early simultaneous (ES) implementation of all four classes of Guideline-Directed Medical Therapy (GDMT) compared to a stepwise (SW) implementation approach in Veterans with heart failure with reduced ejection fraction (HFrEF, EF<40%).
Methods:
This is a single- center, retrospective cohort study conducted at the Washington DC VA Medical Center, a 164- medicine bed tertiary care teaching hospital. GDMT exposure will be determined from the Computerized Patient Record System (CPRS), Veterans Health Information Systems and Technology Architecture (VistA), and HF Dashboard, and its including agents active at discharge and any new starts within 60 days post-discharge. The distinct GDMT classes are defined as one of ARNI (preferred over ACEi/ARB), ACEi/ARB (counted as one class), evidence based β-blocker, MRA, and SGLT-2 inhibitor. Both continued therapies, either active on the discharge medication list, or newly initiated agents will contribute toward the total class count. Dose adjustments or agent substitutions within the same class will not add an additional class. The variables of interest will include patient demographics, comorbidities, baseline heart failure characteristics, medication timing/dosage, laboratory values, number of GDMT classes prescribed, and clinical outcomes. This data will be analyzed to evaluate the progression or improvement of HFrEF in relation to the extent of GDMT utilization. Veterans included in the study consist of those diagnosed with heart failure with reduced ejection fraction (HFrEF, EF <40%) by ICD 10 codes for left ventricular heart failure (I50.1X), systolic heart failure (I50.2X), and combined heart failure (I50.4X), and associated with the index encounter of earliest qualifying HF discharge or earliest outpatient HF visit during the study period of Jan 1, 2022 – Dec 31, 2024. Veterans with pre-index GDMT agent used is permitted. The primary outcome is the number of hospitalization for heart failure exacerbation, all–cause and cardiovascular mortality. The secondary outcome in the incidence of adverse effects and the rates of GDMT continuation. The sample size will be determined by the number of patients meeting predefined inclusion and exclusion criteria within the study cohort. To avoid selection bias, all eligible patients will be included, and no patients will be excluded based on outcomes or treatment exposure. The primary outcome data analysis includes Logistic and Multivariable Cox proportional hazards regression for hospitalization and CV mortality (OR/HRs with 95% CIs).
Results:
In the 60 day landmark analysis, overall there was not statistical difference in any event occurring or the time to an event, however when adjusting for age there was statistical difference in both. In the 30 day analysis, there was a 7 times higher odds of any event occurring in the delayed group vs. the early group. For adherence in the 60 day landmark analysis, the rates of GDMT continuation was significant for each individual agent. In the 30 day analysis, neither adherence measures were significant.
Conclusions:
• Delayed GDMT implementation was associated with higher incidence of events compared to the ES implementation group at 30 days, although those differences did not sustain at 60 days once GDMT was optimized
• No overall significant differences in time-to-event outcomes were identified in either analysis except when adjusting for age as a predictor
• Medication adherence was similar in both landmarks, suggesting outcomes were not explained by adherence alone
• Early implementation may reduce short-term risk, but long-term outcomes may depend on eventual GDMT optimization
• Age was a consistent predictor of outcomes across analysis, suggesting a need for age-tailored treatment strategies
Self Assessment question:
M/C: Which covariant would predict the best approach in regards to the timing in optimizing GDMT in HFrEF patients?
A. Ejection fraction
B. Age
C. Blood pressure
D. Serum creatinine levels
