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. 2021 Sep;44(9):1192-1198.
doi: 10.1002/clc.23664. Epub 2021 Aug 3.

Mortality and guideline-directed medical therapy in real-world heart failure patients with reduced ejection fraction

Peter A McCullough  1 , Hirsch S Mehta  2 , Colin M Barker  3 , Joanna Van Houten  4 , Sarah Mollenkopf  4 , Candace Gunnarsson  5 , Michael Ryan  6 , David P Cork  7
Affiliations

Mortality and guideline-directed medical therapy in real-world heart failure patients with reduced ejection fraction

Peter A McCullough et al. Clin Cardiol. 2021 Sep.

Abstract

Objective: To estimate the prevalence of guideline-directed medical therapy (GDMT) in commercially insured US patients with heart failure with reduced ejection fraction (HFrEF) and examine the effect of GDMT on all-cause mortality. GDMT for HFrEF includes pharmacologic therapies such as β-blockers (BB), angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin (ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter inhibitors to reduce morbidity and mortality.

Methods: Patients in the Optum Integrated File from 2007 to 2019Q3, ≥18 years, with history of HFrEF, were identified. Patients prescribed both a BB and either an ACE-I, ARB, or ARNI during 6-month post-diagnosis were assigned to the GDMT cohort. All others were assigned to the not on GDMT cohort. The GDMT cohort was further classified by those patients with a record of prescription fills for both classes of medications concurrently (GDMT concurrent medication fills). Mortality at 2 years was assessed with a Cox regression model accounting for baseline demographics, comorbidities, and diuretic use.

Results: This study identified 14 880 HFrEF patients, of which 70% had a record of GDMT, and 57% had a record of concurrent prescriptions. Patients in the not on GDMT cohort had 29% increased risk of mortality versus GDMT (hazard ratio 1.29; 95% CI (1.19-1.40); p < .0001). As a sensitivity analysis, the effect of patients not on GDMT compared to GDMT with concurrent medication fills was more pronounced, with a 37% increased mortality risk.

Conclusion: In a real-world population of HFrEF patients, inadequate GDMT confers a 29% excess mortality risk over the 2-year follow-up.

Keywords: goal directed medical therapy; heart failure with reduced ejection fraction; mortality; real-world evidence.

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Conflict of interest statement

All authors contributed significantly to the work and meet the criteria for authorship; all have read and approved the manuscript. Relevant industry relationships and financial interests are as follows: Colin M. Barker, David P. Cork, Peter A. McCullough, Hirsch S. Mehta, Michael Ryan, and Candace Gunnarsson have consulting relationships with Edwards Lifesciences. Dr. Barker is an advisory board member for Medtronic and Boston Scientific. Dr. Cork has a consulting relationship with Abbott Laboratories and participates in a speaker's bureau for Boston Scientific. Dr. Mehta has a consulting relationship with Abbott Laboratories, Boston Scientific and participates in a speaker's bureau for Actelion Pharmaceuticals, Bayer Healthcare Pharmaceuticals, and Bristol‐Myers Squibb Company. Joanna Van Houten and Sarah Mollenkopf, are employees of Edwards Lifesciences, the study sponsor. Standard COI forms have been filled out and provided.

Figures

FIGURE 1
FIGURE 1
Patient attrition diagram. Patients in the Optum database were selected for inclusion in the analysis using the steps below. Eligible HFrEF patients were then classified as GDMT (medications from at least 2 classes), GDMT (concurrent medications from at least 2 classes), and not on GDMT. GDMT, guideline‐directed medical therapy
FIGURE 2
FIGURE 2
Central figure—survival curves from Cox regression models. The survival curves shown are generated from multivariable Cox proportional hazard models and show a higher 2‐year survival rate for patients on guideline‐directed medical therapy (GDMT), particularly for patients on concurrent medication: 86%, GDMT 84%, versus 81% not on GDMT. In the model, patients not on GDMT are 1.29 (compared to GDMT) and 1.37 (compared to GDMT with concurrent medication fills) times more likely to die at any point in time within the 2‐year post‐landmark period. This equates to an excess mortality risk of 29% and 37%, respectively
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