Cardiovascular Disease, Heart Disease, Heart Failure, Heart Failure, Systolic
Conditions
Keywords
Heart Failure with Reduced Ejection Fraction (HFrEF), Guideline Directed Medical Therapy, Real-World Evidence
Brief summary
Heart failure (HF) is a global public health issue that affects more than 63 million people worldwide. The clinical and economic burden of HF on health care systems is substantial. Heart failure with reduced ejection fraction (HFrEF) represents approximately 50% of the HF patient population.The burden of HF is expected to increase substantially as the population ages, and despite improvements in treatment, hospitalisation and mortality rates remain especially high in HFrEF patients. The current guideline recommendation of directed medical therapy for HFrEF combines four drug classes with proven prognostic benefit: Angiotensin receptor-neprilysin inhibitor (ARNI)/angiotensin converting enzyme inhibitors (ACE I)/angiotensin receptor blockers (ARB), betablockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The 2023 ESC (European Society of Cardiology) HF guideline update additionally recommends a rapid in-hospital sequencing approach of guideline-directed medical therapy (GDMT) with frequent physician visits during the first 6 weeks post discharge. Studies investigating the implementation of GDMT in a real-world setting have shown that a significant proportion of patients did not receive the recommended drug combination therapy. Delayed initiation of GDMT contributes to the low number of patients receiving guideline concordant HFrEF therapy, which ultimately may affect patient outcomes. One approach to implement the 2023 ESC guideline updates for heart failure treatment regarding early in-hospital initiation and rapid up-titration of GDMT could be to provide specific training on GDMT recommendations. Such a standardised training is offered to the physicians treating HF patients within selected hospitals of the German Helios hospital network (Helios-GDMT-program). Evidence is needed in order to assess whether in-hospital initiation and up-titration of all phenotype concordant classes of GDMT at hospital discharge can be observed after standardised physician training and whether the GDMT-program implementation also translates into real-world routine outpatient care with respect to use of GDMT and clinical outcomes.
Detailed description
The overall aim of PHRASE-HF is to evaluate the use of GDMT at hospital discharge, the translation of in-hospital implementation and possible maximisation of phenotype-based GDMT into real-world routine outpatient care, HF symptoms, patient reported outcomes (PROs), clinically relevant outcomes (e.g. rehospitalisation, mortality), use of diuretics and concomitant drug classes in patients admitted for in-hospital treatment of HFrEF to sites trained within the Helios-GDMT-program. The analyses will primarily be done in a total study population, and as defined by exploratory objectives in subgroups of interest.
Interventions
None listed
Sponsors
AstraZeneca
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at the time of signing the informed consent * Hospitalised in a participating site and receiving full inpatient treatment (at least 24h hospital stay) * Diagnosis of HFrEF according to the current guidelines of the European Society of Cardiology (ESC) with a left ventricular EF of ≤40% (as measured per echocardiography during the index hospital stay or within 3 months prior to index hospitalisation with available reports from imaging (ejection fraction) at the time of study inclusion) * Treated with a maximum of 2 of the indicated drug classes (ACE-I/ARNI/ARB, BB, MRA, SGLT2i) according to guideline recommendation (GDMT) at admission. * Signed and dated written informed consent prior to enrolment in the study * Willing and capable to fulfil requirements listed in the ICF
Exclusion criteria
* Initial presentation (index hospitalisation) in cardiogenic shock or other kinds of shock * Status post heart transplantation * History of intolerance to one or more GDMT drug classes (ACE-I/ARNI/ARB, BB, MRA, SGLT2i) or significant side effects that led to the discontinuation of two or more substances within one drug class (except from ACE-I/ARB, e.g., if 2 different ACE inhibitors triggered cough, but sartans are tolerated, then the patient is not excluded) * Current or planned participation in a clinical trial * Decision by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures * Pregnancy or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients treated with HFrEF GDMT | Baseline to hospital discharge, on average 6 days after hospitalization/baseline | Proportion of patients treated with phenotype-concordant guideline-recommended HF drug classes and the corresponding doses as noted in patients electronic medical records |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reasons for not having guideline-recommended drug classes or doses | Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months | The reasons for not having maximal phenotype-concordant guideline-recommended HF drug classes as noted in patients electronic medical records will be described as the number and proportion of patients who are not having maximal GDMT drug classes according to each reasons presented |
| Number of outpatient post-discharge visits | Hospital Discharge (on average 6 days after hospitalization/baseline) to 3 months | The number of outpatient visits for heart failure treatment within the first three months after hospital discharge |
| Proportion of patients conducting post-discharge visits | Hospital Discharge (on average 6 days after hospitalization/baseline) to 3 months | Proportion of patients conducting post-discharge visits for heart failure treatment within the first three months after hospital discharge |
| Change of phenotype-concordant guideline-recommended HF drug classes | Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months | The number of patients with change in phenotype-concordant guideline- recommended HF drug classes |
| Number of recommended HF-drug classes | Baseline to hospital discharge, on average 6 days after hospitalization/baseline | The HF-drug classes including the corresponding doses that are recommended in discharge letter at hospital discharge |
| Change of percentage in HFrEF GDMT | Baseline to 12 months | The percentage of patients who are newly initiated on guideline-directed HFrEF medical therapy |
| Absolute change from baseline in NYHA class | Measured at 6 and 12 months | The NYHA classification is a regimen for the classification of heart failure into certain stages according to clearly defined criteria. Treatment of heart failure is usually based on the NYHA classification. Symptoms used to evaluate the stages include dyspnea, nocturia at night, cyanosis, general weakness and fatigue, angina pectoris or cold extremities, edema. NYHA-I: No limitation on resilience. Complete absence of symptoms or signs of exertion when heart disease is diagnosed; NYHA-II: Slight decrease in endurance. Freedom from discomfort during rest and with mild exertion, occurrence of symptoms with increased stress; NYHA-III: Severe limitation of resilience. Freedom from discomfort at rest, occurrence of symptoms even with mild exertion; NYHA-IV: Permanent symptoms, even during rest. |
| Change from Baseline in blood pressure | Baseline to 12 months | Changes in patients blood pressure as noted in patients electronic medical records / |
| Change from Baseline in heart rate | Baseline to 12 months | Changes in patients heart rate as noted in patients electronic medical records |
| Change from Baseline in electrolyte level | Baseline to 12 months | Changes in patients electrolyte level as noted in patients electronic medical records |
| Change from Baseline in potassium level | Baseline to 12 months | Changes in patients potassium level as noted in patients electronic medical records |
| Change from Baseline in estimated glomerular filtrations rate | Baseline to 12 months | Changes in patients estimated glomerular filtration rate as noted in patients electronic medical records |
| Change from Baseline in serum creatinine concentration | Baseline to 12 months | Changes in patients serum creatinine concentration as noted in patients electronic medical records |
| Number of rehospitalization for heart failure | Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months | The number of patients being rehospitalized for heart failure within the observational period |
| Overall Survival | Baseline to 12 months | Number of patients who died during the observational period |
| CV-specific survival | Baseline to 12 months | Number of patients who died due to cardiovascular disease during observation period |
| Absolute change from baseline in Medication Adherence Report Scale (MARS)-5 questionnaire | Measured at 6 and 12 months | The MARS-5 is five-item self-report adherence scale which assesses both intentional and non-intentional non-adherence. Respondents rate the frequency with which the five different medication-taking behaviours occur, scoring each item on a 1-5-point scale with higher scores indicating higher reported adherence. The MARS-5 has been shown to be reliable and valid across a variety of health conditions, including cardiovascular and pulmonary diseases. Only applicable to Prospective cohort. |
| Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score | Measured at 6 and 12 months | The KCCQ is a 23-item questionnaire that quantifies physical limitations, self-efficacy, social interference and quality of life. Summary scores will be examined at each assessment point during follow-up. For each of the assessment periods, descriptive statistics for the observed value, change from baseline and the 95% two-sided confidence interval for the mean change will be presented. The proportions of participants with overall health status classified as poor, fair, good, and excellent will be examined at each assessment point. Additionally, the proportions of participants who experience clinically meaningful changes in overall health status: improvement (≥5 point increase), deterioration (≥5 point decrease), and stable (\<5 point increase or decrease) will be examined at each assessment point. Only applicable to Prospective cohort |
| Absolute change from baseline in PROMIS Global Health 10 | Measured at 6 and 12 months | The PROMIS 10 is a validated comprehensive and accessible set of tools used to measure self-reported physical, mental and social health; including symptoms, function and general perceptions of health and wellbeing. The PROMIS 10 consists of ten items that measure physical health, physical functioning, general mental health, emotional distress, satisfaction with social activities and relationships, ability to carry out usual social activities and roles, pain, fatigue and overall quality of life. |
| Absolute change from baseline in the Nine-Item Patient Health Questionnaire (PHQ-9) | Measured at 6 and 12 months | HF is associated with depressive disorders and manifest depressions. The PHQ-9 that capture depressed mood and anhedonia has been validated as an ultra-brief screening tool with some evidence of responsiveness. The PHQ-9 score is obtained by adding the score for each question (total points). A PHQ-9 score ranges from 0-27, to determine whether they meet criteria for a depressive disorder. |
| Number of diuretics changes | Baseline to 12 months | The number of patients who experience a switch in their diuretic medication drug class as noted in patients electronic medical record |
| Reasons for GDMT adjustments | Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months | The reasons for guideline-directed medical therapy changes as noted in patients electronic medical records will be described as the number and proportion of patients who experienced adjustment in guideline-directed medical therapy according to each reasons presented |
| Number of concomitant medication changes | Baseline to 12 months | The number of patients who experience a switch in their concomitant medication drug class as noted in patients electronic medical record |
Countries
Germany
Outcome results
None listed