Trends in the Prescribed Doses of Loop Diuretics in Patients With Heart Failure Prescribed Dapagliflozin or Empagliflozin in Japan ― An Interrupted Time Series Analysis ―

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Heart failure. Intervention: Publication of the JCS/JHFS 2021 heart failure guideline vs. Before guideline publication. Primary outcome: Change in trend of prescribed dose of furosemide in the empagliflozin-prescribed group (MD -0.2180 mg/month, p=0.0485).

Q: What does this research mean for the field?

Publication of the JCS/JHFS 2021 heart failure guideline was associated with significant decreases in prescribed doses of oral loop diuretics among heart failure patients receiving SGLT2 inhibitors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ryosuke Miura; Kouji Okada

doi:10.1253/circrep.cr-26-0142

September 10, 2026Circulation ReportsOpen Access

Trends in the Prescribed Doses of Loop Diuretics in Patients With Heart Failure Prescribed Dapagliflozin or Empagliflozin in Japan ― An Interrupted Time Series Analysis ―

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Key result

Updated 2021 heart failure guidelines are linked to reduced oral loop diuretic doses in empagliflozin-treated patients.

MD -0.2180 mg/month
P=0.0485

Why the study?

Real-world evidence regarding changes in loop diuretic dosing in heart failure patients receiving SGLT2 inhibitors is limited.

Does publication of the JCS/JHFS 2021 guideline reduce prescribed doses of oral loop diuretics in heart failure patients receiving dapagliflozin or empagliflozin?

Key Points

To evaluate changes in prescribed doses of oral loop diuretics in patients with heart failure receiving dapagliflozin or empagliflozin before and after publication of the JCS/JHFS 2021 guideline.
Conducted an interrupted time series analysis of patients with heart failure prescribed dapagliflozin or empagliflozin across defined time segments before and after guideline publication.
Evaluated monthly dose changes for oral loop diuretics (azosemide, furosemide, and torsemide) using autoregressive models, assessing serial autocorrelation, heteroscedasticity, and seasonality.
In the empagliflozin group from April 2021 to November 2021, significant monthly dose decreases occurred for azosemide (-0.1756 mg/month; P=0.0360), furosemide (-0.2180 mg/month; P=0.0485), and torsemide (-0.0387 mg/month; P=0.0378).
In the dapagliflozin group from April 2021 to November 2021, prescribed doses of azosemide showed a statistically significant downward trend (-0.8221 mg/month; P=0.0260).
An immediate statistically significant dose increase after guideline release occurred only in patients prescribed empagliflozin and torsemide (0.2511 mg/month; P=0.0128).

Study Design

Type

Observational

Multicenter

Yes

Structured PICO

Does publication of the JCS/JHFS 2021 guideline reduce prescribed doses of oral loop diuretics in heart failure patients receiving dapagliflozin or empagliflozin?

P

Population

Patients with heart failure in Japan receiving dapagliflozin or empagliflozin and an oral loop diuretic, evaluated using a nationwide hospital database to observe prescribing trends.

E

Exposure

Publication of the JCS/JHFS 2021 Guideline Focused Update on Diagnosis and Treatment of Acute and Chronic Heart Failure (recommending adjustment of loop diuretic doses with SGLT2 inhibitors).

C

Comparator

The time period prior to the publication of the JCS/JHFS 2021 guideline.

O

Outcome

Change in trends in the mean prescribed doses of oral loop diuretics (azosemide, furosemide, torsemide) measured in mg/month.

Main Result

Mean Difference: -0.218

p-value: p=0.0485

Publication of the JCS/JHFS 2021 heart failure guidelines was associated with real-world decreases in the prescribed doses of oral loop diuretics among patients receiving concomitant SGLT2 inhibitors.

Limitations

Database only includes data from DPC hospitals and does not reflect general practitioner prescribing, possibly overrepresenting severe cases.
Use of aggregated monthly data prevents direct tracking of individual patient dose reductions.
Inability to extract data on left ventricular ejection fraction or NYHA class to assess heart failure severity.
The study period for dapagliflozin after its heart failure indication approval but before guideline publication was too short to provide adequate statistical power.
Database only includes data from DPC hospitals and does not reflect general practitioner prescriptions, potentially overrepresenting severe conditions.
Inability to extract raw patient data limits direct assessment of individual dose reductions.
The same patient population cannot be observed over time, causing differences in patient backgrounds across periods.
Accuracy of ICD-10 diagnoses cannot be verified from raw data.
LVEF and NYHA class information could not be extracted, preventing assessment of heart failure severity.
The study period for dapagliflozin was too short to provide adequate statistical power.

Implication

May support lower loop diuretic doses with SGLT2 inhibitors post-guideline; extends observational data on implementation but leaves outcomes untested.

Abstract

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors and loop diuretics have beneficial diuretic effects in patients with heart failure but may increase the risk of excessive water loss. Therefore, clinical guidelines recommend adjustment of loop diuretic doses when these agents are used concomitantly. However, real-world evidence regarding changes in loop diuretic dosing is limited. This study evaluated changes in prescribed doses of oral loop diuretics in patients with heart failure receiving dapagliflozin or empagliflozin before and after publication of the JCS/JHFS 2021 Guideline Focused Update on Diagnosis and Treatment of Acute and Chronic Heart Failure.

Discussion

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Cite This Study

Miura et al. (2026) conducted an observational in Heart failure. Publication of the JCS/JHFS 2021 heart failure guideline vs. Before guideline publication was evaluated on Change in trend of prescribed dose of furosemide in the empagliflozin-prescribed group (MD -0.2180 mg/month, p=0.0485).

synapsesocial.com/papers/6ad0fcf33afa093ea9ad00b1 https://doi.org/10.1253/circrep.cr-26-0142

Topics

HFrEF treatment

Heart failure

SGLT2 inhibitors in heart failure

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Trends in the Prescribed Doses of Loop Diuretics in Patients With Heart Failure Prescribed Dapagliflozin or Empagliflozin in Japan ― An Interrupted Time Series Analysis ―

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Trends in the Prescribed Doses of Loop Diuretics in Patients With Heart Failure Prescribed Dapagliflozin or Empagliflozin in Japan ― An Interrupted Time Series Analysis ―

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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