Prescribing Improvement Strategies for Heart Failure

(Nudge Trial)

Overseen By Eric E Glenn

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: In training status

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

89 Participants Needed

Trial Summary

What is the purpose of this trial?

This study addresses a critical gap of care for Veterans with heart failure (HF). Only 1/3 or fewer eligible Veterans are receiving recommended SGLT2 and MRA therapies that save lives and prevents HF hospitalizations. The investigators will compare the effect of clinician directed nudges as strategies to improve the health of Veterans with HF.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the drug Dapagliflozin in treating heart failure?

Research shows that Dapagliflozin, originally an antidiabetic drug, can reduce the risk of hospitalization and death from heart problems in patients with heart failure, making it an effective treatment option. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Research shows that medications like dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin, which are used for heart and kidney health, are generally safe. They have been studied in many patients and are linked to fewer serious health problems compared to not using them. ^{1 3 5 6 7}

How does the drug empagliflozin differ from other treatments for heart failure?

Empagliflozin is unique because it is a sodium-glucose co-transporter-2 (SGLT2) inhibitor, which not only helps manage blood sugar levels but also reduces the risk of hospitalization and cardiovascular death in heart failure patients. This dual benefit makes it stand out compared to traditional heart failure treatments that primarily focus on heart function. ^{2 8 9 10 11}

Research Team

Sandesh Dev, MD

Principal Investigator

Southern Arizona VA Health Care System, Tucson, AZ

Eligibility Criteria

This trial is for primary care and cardiology clinicians at the Southern AZ VA Health Care System who work in outpatient clinics. Clinicians still in training, like residents or fellows, cannot participate.

Inclusion Criteria

This criterion includes primary care and cardiology clinicians who work in the outpatient clinic setting at the Southern AZ VA Health Care System.

Exclusion Criteria

Clinicians who are in training status (resident, fellow) will be excluded.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Clinicians receive informational alerts and peer comparison feedback to improve prescribing of SGLT2 and MRA therapies for heart failure patients

6 months

Ongoing clinician interactions via secure email and alerts

Follow-up

Participants are monitored for safety and effectiveness after intervention

30 days

Treatment Details

Interventions

• Informational Nudge

Trial Overview The study tests two methods to encourage better prescription practices for heart failure: a peer comparison report and an alert system. It aims to see if these 'nudges' can improve the health of Veterans by increasing the use of life-saving SGLT2 and MRA therapies.

Participant Groups

Group I: Control Active Control 1 Intervention

No alert or peer comparison

Group II: Peer Comparison Report Active Control 1 Intervention

Clinicians assigned to peer comparison, will receive messages by secure email every two weeks regarding their SGLT2i and MRA prescribing performance.

Group III: Alert Active Control 1 Intervention

Clinicians in the alert arm will receive an alert two business days prior to a patient's upcoming appointment. Clinicians will receive approximately two alerts per week.

Group IV: Alert and Peer Comparison Active Control 2 Interventions

The combined alert and peer comparison arm will receive both interventions.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

Findings from Research

Dapagliflozin, when added to standard treatment for heart failure with reduced ejection fraction (HFrEF), significantly improves patient outcomes, increasing quality-adjusted life years (QALYs) from 6.33 to 6.92, while the cost of treatment rises from approximately 559 USD to 1745 USD.

The cost-effectiveness analysis shows that dapagliflozin is a cost-effective option for HFrEF patients, with an incremental cost-effectiveness ratio (ICER) of 1991 USD/QALY, and it remains cost-effective for 87% of scenarios at a willingness to pay threshold of 5131 USD/QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-utility analysis of add-on dapagliflozin treatment in heart failure with reduced ejection fraction. Krittayaphong, R., Permsuwan, U.[2021]

Dapagliflozin is more cost-effective than empagliflozin for preventing cardiovascular death in heart failure patients, with a cost needed to treat (CNT) of $528,770 compared to $1,018,368 for empagliflozin, based on data from major clinical trials.

The annualized number needed to treat (aNNT) to prevent one cardiovascular death was significantly lower for dapagliflozin (110) than for empagliflozin (204), indicating that dapagliflozin may provide better clinical outcomes for the cost in heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Dapagliflozin Versus Empagliflozin on Cardiovascular Death in Patients with Heart Failure Across the Spectrum of Ejection Fraction: Cost per Outcome Analysis. Alnsasra, H., Tsaban, G., Solomon, A., et al.[2023]

Dapagliflozin, when added to usual care for patients with heart failure and mildly reduced or preserved ejection fraction, significantly improves quality-adjusted life years (QALYs) and life expectancy, with increases of 0.231 QALYs and 0.354 life-years in the UK.

The treatment is projected to be cost-effective across the UK, Germany, and Spain, with high probabilities (91% in the UK, 89% in Germany, and 92% in Spain) of being within acceptable cost-effectiveness thresholds, making it a viable option for healthcare systems in these countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A European health-economic analysis of the DELIVER trial. Booth, D., Davis, JA., McEwan, P., et al.[2023]

Empagliflozin, when added to standard care for heart failure patients, significantly improves quality-adjusted life expectancy by 0.15 QALYs at an additional cost of 1,594 euros, making it a cost-effective treatment option.

The probability of empagliflozin being cost-effective compared to standard care alone is high, at 77.6% for a willingness-to-pay threshold of 35,000 euros per QALY, indicating strong economic viability in the Finnish healthcare system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Empagliflozin in Combination with Standard Care versus Standard Care Only in the Treatment of Heart Failure Patients in Finland. Hallinen, T., Kivelä, S., Soini, E., et al.[2023]

Dapagliflozin, when added to standard therapy for heart failure with reduced ejection fraction (HFrEF), significantly improves patient outcomes, increasing life-years from 5.62 to 6.20 and quality-adjusted life-years (QALYs) from 4.13 to 4.61, while also reducing hospitalizations for heart failure.

The treatment is considered cost-effective across the UK, Germany, and Spain, with incremental cost-effectiveness ratios well below the commonly accepted thresholds, indicating that it provides good value for the healthcare systems in these countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of dapagliflozin as a treatment for heart failure with reduced ejection fraction: a multinational health-economic analysis of DAPA-HF. McEwan, P., Darlington, O., McMurray, JJV., et al.[2021]

Immediate initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure significantly reduces heart failure events and cardiovascular mortality compared to standard therapy, demonstrating its efficacy in improving patient outcomes.

Both immediate and delayed initiation of dapagliflozin are cost-effective options, but immediate initiation offers greater clinical benefits, yielding nearly 10% more quality-adjusted life years (QALYs), making it the preferred standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure. Miller, RJH., Chew, DS., Qin, L., et al.[2023]

SGLT2 inhibitors (SGLT2i) significantly reduce all-cause mortality (hazard ratio 0.85) and major adverse cardiovascular events (MACE) (hazard ratio 0.91) in patients with type 2 diabetes and cardiovascular disease, based on a meta-analysis of 46,969 patients across six trials.

Among the SGLT2i, empagliflozin was found to be the most effective in preventing cardiorenal events and mortality, while ertugliflozin was less effective compared to other SGLT2i, indicating that treatment choice can impact patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of SGLT2 Inhibitors: A Multiple-Treatment Meta-Analysis of Clinical Decision Indicators. Martínez-Vizcaíno, V., Díez-Fernández, A., Álvarez-Bueno, C., et al.[2021]

Empagliflozin has been shown to be effective in improving outcomes for patients with heart failure, regardless of their kidney function status, indicating its broad applicability in this patient population.

The study included a diverse group of patients with varying levels of kidney risk, which supports the safety and efficacy of empagliflozin across different kidney health categories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In chronic HF, empagliflozin reduced a composite of CV death or HF hospitalization across kidney risk categories. Ziaolhagh, A., Molony, DA.[2023]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

A meta-analysis of 10 randomized controlled trials involving 15,373 heart failure patients found no significant differences in clinical outcomes among the SGLT2 inhibitors empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin regarding heart failure hospitalizations, cardiovascular deaths, and all-cause mortality.

Despite the lack of differences in treatment effects, the analysis highlighted the need for further research due to the variability in study results and the wide confidence intervals observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials. Teo, YH., Yoong, CSY., Syn, NL., et al.[2022]

In a study of 441 outpatients with heart failure with reduced ejection fraction (HFrEF), 45% were eligible for both dapagliflozin and empagliflozin, indicating a significant potential for these SGLT2 inhibitors to be used in real-world clinical practice.

When excluding the NT-proBNP threshold from eligibility criteria, the proportion of patients eligible for dapagliflozin increased to 86%, suggesting that broader application of these medications could further reduce morbidity and mortality in HFrEF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-glucose co-transporter-2 inhibitors eligibility in patients with heart failure with reduced ejection fraction. Monzo, L., Ferrari, I., Cicogna, F., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-utility analysis of add-on dapagliflozin treatment in heart failure with reduced ejection fraction. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of Dapagliflozin Versus Empagliflozin on Cardiovascular Death in Patients with Heart Failure Across the Spectrum of Ejection Fraction: Cost per Outcome Analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A European health-economic analysis of the DELIVER trial. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Empagliflozin in Combination with Standard Care versus Standard Care Only in the Treatment of Heart Failure Patients in Finland. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of dapagliflozin as a treatment for heart failure with reduced ejection fraction: a multinational health-economic analysis of DAPA-HF. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of SGLT2 Inhibitors: A Multiple-Treatment Meta-Analysis of Clinical Decision Indicators. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

In chronic HF, empagliflozin reduced a composite of CV death or HF hospitalization across kidney risk categories. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Sodium-glucose co-transporter-2 inhibitors eligibility in patients with heart failure with reduced ejection fraction. [2021]