Dapagliflozin: Best for Heart Failure With High Pressure Flow-Based on Real World Data

Understanding Heart Failure and Its Impact

Heart failure (HF) is a chronic condition affecting over 26 million people worldwide. It occurs when the heart can’t pump enough blood to meet the body’s needs, leading to symptoms like shortness of breath, fatigue, and swelling in the legs and abdomen. Managing HF is challenging due to its progressive nature and the significant impact it has on patients’ quality of life.Towards the end the article will provide an idea of how much Dapaglifozin can improve a patient’s quality of life.

Introducing Dapagliflozin: A Game-Changer in HF Management

Dapagliflozin, a medication initially developed to treat type 2 diabetes, belongs to a class of drugs known as sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors). Recent research has revealed that dapagliflozin offers substantial benefits for patients with heart failure, even for those without diabetes.

A Closer Look at the Recent Study

A recent multicenter, real-world study conducted across six Italian university hospitals evaluated the effectiveness of dapagliflozin in patients with chronic heart failure with reduced ejection fraction (HFrEF). The ejection fraction (EF) is a key measure of how well the heart pumps blood; in HFrEF, this value is significantly decreased (less than 40%).

Why the Study from Cardiovascular Diabetology Matters

Unlike prior studies that primarily focused on left ventricular ejection fraction (LVEF) as the key parameter, this study introduced a novel hemodynamic classification system that accounts for variations in congestion and perfusion states (profiles A-D) This will be further elaborated on later. This approach highlights how Dapagliflozin is particularly effective in patients with congestive profiles (profiles B and D), who typically present with worse prognosis. 

Personalized Treatment: This underscores the importance of tailoring therapies based on individual hemodynamic states rather than relying solely on LVEF, suggesting that patients with poorer profiles may derive greater benefits. Finally the study is based on real world patients not highly regimented research studies with cardiologists which takes into account “imperfect patients” that forget to take medicine, miss follow ups etc which leads to more accurate estimates of real-world behaviour. 

Study Design and Participants

• Participants: 240 patients with HFrEF.
• Duration: 6 months.
• Intervention: Addition of dapagliflozin (10 mg once daily) to their existing heart failure medications.
• Existing Medications: Included beta-blockers, ACE inhibitors or ARBs, mineralocorticoid receptor antagonists, and, in some cases, angiotensin receptor-neprilysin inhibitors (ARNIs).

Key Quantitative Findings

Significant Improvement in Heart Function

1. Left Ventricular Ejection Fraction (LVEF):
   • Baseline: Average LVEF was approximately 30%.
   • After 6 Months: Increased to an average of 35%.
   • Magnitude of Change: An improvement of about 5 percentage points, representing a relative increase of approximately 17%.
2. Left Ventricular End-Diastolic Volume (LVEDV):
   • Baseline: Average LVEDV was around 200 milliliters.
   • After 6 Months: Decreased to approximately 180 milliliters.
   • Magnitude of Change: A reduction of 20 milliliters, indicating decreased heart chamber size and reduced strain.
3. Stroke Volume Index (SVi):
   • Increase of about 10%, enhancing the amount of blood pumped with each heartbeat relative to body surface area.

Reduction in Heart Failure Symptoms

1. E/e’ Ratio (Indicator of Heart Pressure):
   • Decrease of approximately 15%, suggesting reduced pressure inside the heart and improved relaxation during filling.
2. Pulmonary Artery Systolic Pressure (sPAP):
   • Baseline: Average sPAP was about 40 mmHg.
   • After 6 Months: Decreased to around 35 mmHg.
   • Magnitude of Change: A reduction of 5 mmHg, easing the burden on the right side of the heart and lungs.

Benefits Across Different Patient Groups

Patients were categorized into four hemodynamic profiles based on their heart’s blood flow (stroke volume) and pressure (E/e’ ratio):

1. Profile A: Normal flow, normal pressure.
2. Profile B: Normal flow, high pressure.
3. Profile C: Low flow, normal pressure.
4. Profile D: Low flow, high pressure.

Notable Improvements in Profiles B and D (Congestive Profiles):

• Right Ventricular Function:
  • Tricuspid Annular Plane Systolic Excursion (TAPSE):
    • Increase of about 20%, indicating better right heart pumping ability.
• Reduced Need for Diuretics:
  • Furosemide Dose:
    • Decreased by approximately 30 mg per day in congestive profiles, reducing reliance on high-dose diuretics.

Drastic Reduction in Hospitalizations

• Rehospitalization Rates Over 6 Months:
  • Dapagliflozin Group: Only 1.25% of patients were rehospitalized due to worsening heart failure.
  • Comparison Groups:
    • Historical Data (Without Dapagliflozin): Rehospitalization rates ranged from 15% to 19%.
  • Magnitude of Change: An over 90% reduction in rehospitalization rates compared to historical data.

Stable Kidney Function and Safety

• Estimated Glomerular Filtration Rate (eGFR):
  • No significant change over the 6-month period, indicating that dapagliflozin did not adversely affect kidney function.
• Adverse Effects:
  • Minimal side effects reported, and the medication was well-tolerated by patients.

Improved Quality of Life

• Patient-Reported Outcomes:
  • Significant improvements in symptoms like fatigue and shortness of breath.
  • Enhanced daily activity levels, with patients reporting better capacity for exercise and routine tasks.

Understanding the Impact

The quantitative improvements observed in this study underscore the substantial benefits of dapagliflozin for heart failure patients:

• Heart Function: A 5% absolute increase in LVEF can translate to meaningful clinical improvements, reducing symptoms and slowing disease progression.
• Symptom Relief: Reductions in heart pressures and volumes alleviate congestion, leading to decreased swelling and breathlessness.
• Hospitalizations: Reducing rehospitalization rates by over 90% significantly improves patient outcomes and reduces healthcare costs.

Mechanism of Action

Dapagliflozin works by inhibiting the SGLT2 protein in the kidneys, leading to:

• Glucose and Sodium Excretion: Helps eliminate excess sugar and salt, reducing blood volume.
• Diuretic Effect: Promotes mild diuresis (increased urine production), which helps reduce fluid overload.
• Blood Pressure Reduction: Lowers both systolic and diastolic blood pressure, easing the heart’s workload.

Why This Matters for Heart Failure Patients

• Enhanced Treatment Outcomes: Dapagliflozin provides an additional mechanism to improve heart function beyond traditional heart failure medications.
• Symptom Management: Patients may experience fewer symptoms and better exercise tolerance.
• Medication Simplification: Potentially reduces the need for high doses of other medications like diuretics.
• Quality of Life: Improvements in heart function and symptoms contribute to better overall well-being.

Conclusion and What this means for Patients!

It may be difficult at times to appreciate all of the theoretical numbers presented above and what they mean for the patient’s day-to-day life. The following information will illustrate what consuming Dapagliflozin after 6 months does for a patient in terms of climbing three flights of stairs.

Before Treatment to get to the 3 flights of stairs:

• Could take up to 5-10 minutes to reach their apartment on the third floor
• Might avoid using stairs altogether, opting for elevators when available

After Regular Use of Dapagliflozin:

• Might be able to reach the third floor with only one brief stop
• Could potentially climb all three flights in 2-3 minutes
• Might feel more confident using stairs in various settings

The quality of life difference between stopping once briefly to get to the 3rd floor in about 2 minutes versus 10 minutes with frequent stops is a major quality of life difference.

Next Steps for Patients

If you or someone you know is managing heart failure, consider discussing dapagliflozin with your healthcare provider. It’s essential to evaluate:

• Suitability: Whether dapagliflozin is appropriate based on your specific health condition.
• Medication Interactions: How it fits with your current medications.
• Monitoring: Establishing a plan to monitor heart function and kidney health during treatment.

Remember: Always consult a healthcare professional before starting any new medication.

Frequently Asked Questions (FAQs)

How much can dapagliflozin improve my heart’s ejection fraction?

In the study, patients saw an average increase of about 5 percentage points in their ejection fraction over six months, which is a significant improvement for individuals with HFrEF.

Will dapagliflozin reduce my symptoms of heart failure?

Yes, many patients experienced reduced symptoms such as shortness of breath and swelling due to decreased heart pressures and improved heart function.

Is dapagliflozin safe for long-term use?

The study showed that dapagliflozin was well-tolerated over six months with no significant adverse effects on kidney function. However, long-term safety should be monitored by your healthcare provider.

Can dapagliflozin help me avoid hospital visits?

The study demonstrated a dramatic reduction in rehospitalization rates, suggesting that dapagliflozin can help prevent worsening heart failure that leads to hospital admissions.

Do I need to have diabetes to benefit from dapagliflozin?

No, dapagliflozin has been shown to benefit heart failure patients regardless of their diabetes status. 

Disclaimer: This article is for informational purposes only and does not substitute professional medical advice. Always consult a qualified healthcare provider for guidance tailored to your health situation.

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