Medical therapy

Clinical outcomes in patients with HFrEF related to titration of medical therapy

In patients with chronic heart failure with reduced ejection fraction (HFrEF), characteristics such as blood pressure and recent hospitalization status are associated with a likelihood of escalation and de-escalation of inhibitor therapy. angiotensin converting enzyme (ACE) and β-blocker. These findings were published in the American Journal of the Heart.

An analysis was conducted and included patients enrolled in the international, multicenter, randomized, controlled trial Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). Recognizing that patient characteristics related to dose titration and clinical outcomes following dose titration remain poorly understood in patients with HFrEF, researchers sought to examine the use and dosing of HFrEF inhibitors. ACE and β-blockers in these people at baseline and at 6 months follow-up. -at the top.

At baseline and at 6 months, the drug dosage of evidence-based ACE inhibitors and β-blockers for each participant was categorized against the target dose specified in the clinical management guidelines for the patient. ‘ic. The dosing groups were patients receiving no drug, patients receiving 1% to 49% of the target dose, patients receiving 50% to 99% of the target dose, or patients receiving 100% or more of the target dose.

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Patients were then categorized into 4 dose trajectory groups for each drug class, based on the change in dose category between baseline and 6 months. These trajectory groups were stable under-target (dose category remained constant and below target, including patients who remained on no drug); stable target dose group (dose category remained constant and at target); dose escalation group (increasing the dose category, including the initiation of treatment); and dose de-escalation group (decrease in dose category, including discontinuation). All participants were assigned to separate dose trajectory groups for ACE inhibitors and β-blockers, regardless of the other drug class.

The analysis had 3 pre-specified co-primary endpoints: all-cause mortality, a composite of cardiovascular mortality or HF hospitalization, and a composite of all-cause mortality and all-cause hospitalization. The study was designed as 2 identical parallel analyses, 1 for ACE inhibitors and 1 for β-blocker therapy.

A total of 1999 participants from the HF-ACTION trial were included in the trajectory analyzes of ACE inhibitors and β-blockers. The majority of patients were treated with stable sub-target ACE inhibitor doses (59.4%), compared to the stable target group (25.6%), dose escalation group (6 .3%) and the dose de-escalation group (8.7%).

The majority of patients were treated with β-blocker doses that were stable sub-target β-blocker doses (50.1%), compared to the stable target group (29.2%), the dose escalation (12.7%) and the dose de-escalation group. group (8.1%).

Study results showed that with ACE inhibitors and β-blockers, hospitalization for HF within 6 months prior to enrollment was associated with increased dose (odds ratio [OR], 2.32; 95% CI, 1.58-3.42 with ACE inhibitors and OR, 1.42; 95% CI, 1.05-1.90 with β-blockers). Additionally, higher systolic blood pressure per 1 mm Hg increase was also associated with increased dose (OR, 1.01; 95% CI, 1.00-1.03 with ACE inhibitors and OR, 1.01; 95% CI, 1.00-1.02 with β-blockers).

Hospitalization for any cause at 6 months before enrollment, which included both CI and non-CI causes, was associated with a decrease in dose (OR, 1.60; 95% CI, 1.14- 2.25 with ACE inhibitors and OR, 1.67; 95% CI, 1.20-2.33 with β-blockers).

After adjusting for patient characteristics, relative to a stable target dose, decreasing the dose of either drug was associated with higher all-cause mortality (adjusted relative risk [aHR], 1.64; 95% CI, 1.11-2.42 with ACE inhibitors and aHR, 1.62; 95% CI, 1.04-2.53 with β-blockers). Compared to a stable target dose, the de-escalation of the β-blocker dose (aHR, 1.98; 95% CI, 1.36-2.87) and stable sub-target β-blocker dose (aHR , 1.49; 95% CI, 1.18-1.87) were associated with greater cardiovascular mortality or hospitalization for HF.

Limitations of the study include that because it used the HF-ACTION clinical trial cohort, the results may not reflect actual clinical practice. Additionally, “this observational study cannot definitively determine cause and effect relationships.”

The researchers concluded that future studies are needed to develop targeted interventions to prevent the de-escalation of guideline-directed medical treatment for patients with HFrEF, particularly in those at high risk of treatment discontinuation who present. a particularly high risk of occurrence of clinical events. . “Similarly, in cases where [guideline-directed medical therapy] is appropriately defused due to the development of contraindications or true intolerance, additional consideration of advanced heart failure therapies or palliative care may be warranted,” the researchers wrote.

Disclosure: One of the study authors declared affiliations with biotechnology, pharmaceutical and/or device companies. Please see the original citation for a full list of author disclosures.


Pierce JB, Mentz RJ, Sun JL, et al. Medical treatment titration and clinical outcomes in heart failure patients with reduced ejection fraction: results from the HF-ACTION trial. Am Heart J. Published online May 29, 2022. doi:10.1016/j.ahj.2022.05.018