Dapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy

Cheng-Hsin General Hospital

Status and phase: Completed; Phase 4

Conditions: Hypotension; Heart Failure

Treatments: Drug: Sacubitril-Valsartan; Drug: Dapagliflozin; Drug: Beta blocker; Drug: Mineralocorticoid Receptor Antagonist; Device: Cardiac resynchronization therapy and/or implantable cardioverter defibrillator

Study type: Interventional

Funder types: Other

Identifiers

NCT04575675

ChenghsinGH

Details and patient eligibility

About

The DAPA-HF trial demonstrated that dapagliflozin was able to reduce the risk of worsening heart failure events and cardiovascular death comparing to placebo in patients with reduced ejection fraction further to standard of care. However, hypotensive patients who generally have higher risks comparing to normotensive patients, were under represented in the DAPA-HF. The investigators aimed to evaluate clinical effects of dapagliflozin on hypotensive heart failure patients receiving chronic sacubitril/valsartan treatment.

Full description

The DAPA-HF trial demonstrated that dapagliflozin was able to reduce the risk of worsening heart failure (HF) events and cardiovascular death comparing to placebo in patients with reduced ejection fraction further to standard of care. However, hypotensive patients who generally have higher risks comparing to normotensive patients, were under represented in the DAPA-HF. The investigators aimed to evaluate clinical effects of dapagliflozin on hypotensive HFrEF patients receiving chronic sacubitril/valsartan (Sal/Val) treatment.

This is an investigator-initiated, interventional, prospective. open-label study. The inclusion criteria were (1) chronic symptomatic HF with New York Heart Association (NYHA) class II-IV and LVEF less than 40%, (2) treatment with stable and maximal tolerable dose of Sac/Val, beta-blocker with or without mineralocorticoid receptor antagonist (MRA), (3) 6-minute walking-distance (6MWD)≥ 100meters and ≤425 meters at enrollment, (4) systolic blood pressure ≤100 mmHg at enrollment. The exclusion criteria were (1) type 1 diabetes mellitus, (2) patients previously treated with any sodium glucose co-transporter 2 inhibitor (SGLT2i).

After applying the inclusion and exclusion criteria, if the participants had type 2 diabetes mellitus, the participants will receive dapagliflozin 10mg daily directly. If the participants did not have history of diabetes mellitus, the participants will be allocated to either receiving dapagliflozin 10mg daily or receiving standard heart failure treatment without dapagliflozin.

Vital signs and laboratory tests were examined at baseline, 2-week, 4-week and 12-week. Six-minute-walking-test, five-level EuroQol five dimensions (EQ-5D-5L) questionnaire and visual analogue scale (VAS) were collected at baseline and at 12-week.

Enrollment: 78 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• chronic symptomatic HF with New York Heart Association (NYHA) class II-IV and left ventricular ejection fraction (LVEF) less than 40%
• treatment with stable and maximal tolerable dose of Sac/Val, beta-blocker with or without mineralocorticoid receptor antagonist
• 6-minute walking-distance (6MWD)≥ 100meters and ≤425 meters at enrollment
• systolic blood pressure ≤100 mmHg at enrollment

Exclusion criteria

• hemodialysis
• severe co-morbidities with life expectancy less than 1 year
• type 1 diabetes mellitus
• ever treated with any type of sodium glucose cotransporter 2 inhibitor (SGLT2i)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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78 participants in 2 patient groups, including a placebo group

Dapagliflozin

Experimental group

Description:

Dapagliflozin with standard-of-care therapies for heart failure, including sacubitril/valsartan, beta-blocker, MRA, ICD and CRT

Treatment:

Drug: Mineralocorticoid Receptor Antagonist

Drug: Beta blocker

Device: Cardiac resynchronization therapy and/or implantable cardioverter defibrillator

Drug: Dapagliflozin

Drug: Sacubitril-Valsartan

Standard of care

Placebo Comparator group

Description:

Standard-of-care therapies for heart failure, including sacubitril/valsartan, beta-blocker, MRA, ICD and CRT

Treatment:

Drug: Mineralocorticoid Receptor Antagonist

Drug: Beta blocker

Device: Cardiac resynchronization therapy and/or implantable cardioverter defibrillator

Drug: Sacubitril-Valsartan