Guideline Implementation, Drug Sequencing, and Quality of Care in Heart Failure: TITRATE-HF
Published Congress: ESC Heart Failure 2024

Link: https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14604

Dr. Aysu Oktay

Background:
In patients with heart failure with reduced ejection fraction (HFrEF), the optimal therapyt based on current cardiology guidelines consists of four major pharmacological agents: ACEI/ARB/ARNI, beta-blockers, MRAs, and SGLT2 inhibitors (quadruple medical therapy - GDMT). Recent meta-analyses have shown that the simultaneous initiation of drug groups in GDMT is associated with a reduction in mortality rates in heart failure patients.
Reflecting the treatment recommendations outlined in the guidelines into real-world clinical practice is challenging. Data from the CHECK-HF study in the Netherlands found that although the prescription rate of GDMT in the country is promising, however, the usage rate in HFrEF patients is only about one-third. Similarly, the 2021 ESC Heart Failure Guidelines recommend that each of the four agents should be initiated without delay.
Significant study results, such as those from STRONG-HF, support that starting treatment promptly, as per guideline recommendations, significantly reduces mortality. Despite increasing evidence supporting a high-intensity and rapid sequencing approach, like in the STRONG-HF study, adapting this to clinical practice remains difficult. Frequent patient visits, especially within the first three months, are challenging due to technical and personnel shortages, leading to the development of new treatment initiation strategies.

Objective:
The purpose of TITRATE-HF study is to evaluate the adaptability of guidelines to routin clinical practice, obtain prospective data on GDMT sequencing and dose titration strategies, and assess how these strategies impact heart failure patients.

Methods:
The TITRATE-HF study is a multicenter study supported by the Dutch Cardiology Society, aimed at evaluating the implementation of guidelines in daily clinical practice for heart failure (HF) patients. Participants in the study are classified into three groups according to the category of heart failure: De-novo HF: Confirmed HF within the last 3 months, Chronic HF: Confirmed HF within the last 6 months, and Worsening HF: HF confirmed more than 6 months ago or a HF-related event (emergency visit or hospitalization) within the last 6 months. Patients with a life expectancy of less than 1 year, those who had a major cardiovascular event (MI, stroke, open-heart surgery) within the last 6 months, and end-stage heart failure patients scheduled for cardiac transplantation or left ventricular assist device within the last 6 months were excluded from the study.

Results:
A total of 4288 patients from 48 centers were included in the TITRATE-HF study. Among these patients, 1732 presented with de novo HF, 2240 with chronic HF, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and the median left ventricular ejection fraction was 35% (IQR 25-40). A total of 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of these patients achieved the target dose for all drug classes. Additionally, quadruple therapy was more frequently prescribed to patients treated in a specialized HF outpatient clinic compared to a general cardiology outpatient clinic. In each GDMT drug class, non-use rates in HFrEF patients ranged from 19% to 36% due to side effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients were already using one or more GDMT drug classes for indications other than HF. Furthermore, the results indicated that the prescription of SGLT2 inhibitors was adopted more quickly than previous drug classes such as ARNI.

Conclusion:
Current guidelines show significant changes in the initiation and titration of HF medications compared to previous guidelines. The recommendations now favor a "parallel approach" (starting several drugs in combination at low doses and titrating to the maximum tolerated dose) over a "sequential approach" (titrating one drug to the maximum or tolerated dose before starting another). This initial analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort while highlighting the need for improvement in the implementation of quadruple therapy. Importantly, the use and dosage of GDMT are not optimal, and the reasons for this are often unclear. This underscores the necessity for further optimization of GDMT and implementation strategies in HF management.

Interpretations:
The distinct and strong aspect of the TITRATE-HF study compared to other studies is the categorization of HF patients, allowing for subgroup analysis based on age, gender, comorbidity, and clinical parameters. Additionally, unlike other studies, it evaluates the medical treatments and uptitration of not only chronic HF patients but also de novo HF patients. The initial results of the study show that although the prescription rates of quadruple GDMT have improved, the rate of patients reaching the optimal dose is still very inadequate. Furthermore, the results suggest that the presence of specialized HF centers and clinics can facilitate achieving optimal treatment in the follow-up and treatment of HF patients.