Real-world Dapagliflozin Treatment in Patients With Heart Failure in Portugal (EVOLUTION-HF)

Study Overview
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Brief Summary
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Heart failure (HF) is a global, public health issue that affects more than 63 million people worldwide; this burden is expected to increase substantially as the population ages. Despite advancements in treatment, a HF diagnosis still leads to significant morbidity and mortality; there is also an immense impact on patients' health-related quality of life (HRQoL). On May 5, 2020, the US Food and Drug Administration (FDA) announced the approval of dapagliflozin for heart failure with reduced ejection fraction (HFrEF), regardless of whether the patient has diabetes. Subsequently, there have been additional approvals for this indication by regulatory authorities across the globe. Real-world observational data are necessary to describe dapagliflozin use in real-world settings with detailed clinical data on heart failure symptoms, outcomes, and HRQoL.

Detailed Description
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Heart failure (HF) is a global, public health issue that affects more than 63 million people worldwide; this burden is expected to increase substantially as the population ages. Despite advancements in treatment, a HF diagnosis still leads to significant morbidity and mortality; there is also an immense impact on patients' health-related quality of life (HRQoL). On May 5, 2020, the US Food and Drug Administration (FDA) announced the approval of dapagliflozin for heart failure with reduced ejection fraction (HFrEF), regardless of whether the patient has diabetes. Subsequently, there have been additional approvals for this indication by regulatory authorities across the globe. Real-world observational data are necessary to describe dapagliflozin use in real-world settings with detailed clinical data on heart failure symptoms, outcomes, and HRQoL. EVOLUTION-HF will help obtaining relevant insights from clinical practice through the analysis of detailed data on heart failure symptoms/severity for patients receiving dapagliflozin in real-world setting. Study aims are to describe the characteristics of patients newly prescribed dapagliflozin for the treatment of HFrEF, to provide early insights into real-world dapagliflozin treatment patterns, and to describe patients-reported outcomes, medication adherence and work productivity losses in these patients. This observational, longitudinal cohort study will include patients with a physician diagnosis of HFrEF who are initiated on dapagliflozin in clinical practice. The study will include 2 cohorts of patients: one fully retrospective and one prospective cohort, in which patient-reported outcomes (PROs) including quality of life will be collected

Official Title
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Early Treatment of Heart Failure: a Non-interventional Observational Study of Patients With Heart Failure and Initiated on Dapagliflozin in Portugal

Conditions
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Heart Failure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years as of study index date; the study index date is date of initiation of treatment with dapagliflozin Patient received/receiving treatment with dapagliflozin for HFrEF (EF ≤40%) in accordance with the local dapagliflozin product label: Retrospective study: their dapagliflozin initiation was between 1st of March 2021 and 31st of October 2021. Prospective study: their dapagliflozin initiation was ≥30 days and ≤60 days prior to enrollment onto the study Signed and dated informed consent prior to enrollment in the study (only applicable for the prospective cohort, informed consent waiver will be requested for retrospective cohort) Exclusion Criteria: Patient is enrolled less than 30 days following initiation of dapagliflozin Prior treatment with dapagliflozin or other SGLT2i treatment Initiation of dapagliflozin outside of local HF label Diagnosis of Type 1 diabetes prior to enrolment
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective cohort<br>Patients who have initiated treatment with dapagliflozin for HFrEF between 1st of March 2021 and 31st of October 2021 (prior to study initiation date). | |
| Prospective Cohort<br>Patients who have started treatment with dapagliflozin for HFrEF from 1st April 2022 onwards. At least 30 days must have elapsed (but no more than 60 days) from first prescription of dapagliflozin before a patient can be enrolled. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to dapagliflozin treatment discontinuation | Time from dapagliflozin treatment initiation until the time at which participants stop taking the medication for any reason. | Baseline to 12 months | 
| Number of reasons for dapagliflozin treatment discontinuation | Number of reasons for dapagliflozin treatment discontinuation as noted by a health care professional will be extracted and described as the number and proportion of participants who have discontinued dapagliflozin according to each reasons presented. | Baseline to 12 months | 
| Proportion of reasons for dapagliflozin treatment discontinuation | Proportion of reasons for dapagliflozin treatment discontinuation as noted by a health care professional will extracted and described as the number and proportion of participants who have discontinued dapagliflozin according to each reasons presented. | Baseline to 12 months | 
| Number of dapagliflozin treatment changes | The number of participants who switch to another HF medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of dapagliflozin treatment changes | The percentage of participants who switch to another HF medication other than dapagliflozin. | Baseline to 12 months | 
| Number of dapagliflozin treatment discontinuation | The number of participants who discontinued treatment with dapagliflozin. | Baseline to 12 months | 
| Percentage of dapagliflozin treatment discontinuation | The percentage of participants who discontinued treatment with dapagliflozin. | Baseline to 12 months | 
| Time to other HF medication discontinuation | Time from initiation of heart failure medication other than dapagliflozin until the time at which participants discontinued treatment with that medication. | Baseline to 12 months | 
| Number of other heart failure treatment initiation | The number of participants who initiate new heart failure medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of other heart failure treatment initiation | The percentage of participants who initiate new heart failure medication other than dapagliflozin. | Baseline to 12 months | 
| Number of other heart failure treatment dosage changes | The number of participants with dosage changes for heart failure medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of other heart failure treatment dosage changes | The percentage of participants with dosage changes for heart failure medication other than dapagliflozin. | Baseline to 12 months | 
| Number of other heart failure treatment discontinuation | The number of participants who discontinue treatment with heart failure medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of other heart failure treatment discontinuation | The percentage of participants who discontinue treatment with heart failure medication other than dapagliflozin. | Baseline to 12 months | 
| Time to glucose lowering medication discontinuation | Time from initiation of glucose lowering medication until the time at which participants discontinued treatment with that medication. | Baseline to 12 months | 
| Number of glucose lowering medication initiation | The number of participants who initiate new glucose lowering medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of glucose lowering medication initiation | The percentage of participants who initiate new glucose lowering medication other than dapagliflozin. | Baseline to 12 months | 
| Number of glucose lowering medication dosage changes | The number of participants with dosage changes for glucose lowering medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of glucose lowering medication dosage changes | The percentage of participants with dosage changes for glucose lowering medication other than dapagliflozin. | Baseline to 12 months | 
| Number of glucose lowering medication discontinuation | The number of participants who discontinue treatment with glucose lowering medication other than dapagliflozin. | Baseline to 12 months | 
| Percentage of glucose lowering medication discontinuation | The percentage of participants who discontinue treatment with glucose lowering medication other than dapagliflozin. | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score | 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. | Measured at 3, 6 and 12 months | 
| Absolute change from baseline in Medication Adherence Report Scale (MARS)-5 questionnaire | 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. | Measured at 3, 6 and 12 months | 
| Absolute change from baseline in Work Productivity and Activity Impairment (WPAI) score | The WPAI is a validated instrument to measure impairments in paid and unpaid work and activities. It measures absenteeism (work time missed), presenteeism (impairment at work / reduced on-the-job effectiveness) as well as the impairments in unpaid activity because of health problems during the past seven days. It has been validated to quantify work impairments for numerous diseases such as asthma, psoriasis, irritable bowel syndrome, and Crohn's disease, but has not yet been validated for use in heart failure participants. Scores will be derived from the overall work impairment at each timepoint and then changes of from baseline will be reported. Only applicable to Prospective cohort. | Measured at 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Heart Failure with Reduced Ejection Fraction, HFrEF, Dapagliflozin, Real-world