682 Heart Failure with Reduced Ejection Fraction

Case Study B: Heart Failure with Reduced Ejection Fraction

1. Pharmacotherapeutic Plan and Medication Overview

• The plan focuses on:

  • Improving cardiac function

  • Relieving congestion

  • Reducing morbidity and mortality

• Medications prescribed and discontinued optimize therapy based on evidence and guidelines.

Medications:

• Sacubitril/Valsartan (Entresto)

  • Class: Neprilysin inhibitor and angiotensin receptor blocker (ARB)

  • Pharmacodynamics:

  • Sacubitril inhibits neprilysin, increasing natriuretic peptides, leading to:

    • Vasodilation

    • Natriuresis

    • Reverse remodeling

  • Valsartan blocks angiotensin II receptors, resulting in:

    • Reduced vasoconstriction

    • Decreased aldosterone secretion

  • Pharmacokinetics:

  • Converted to active metabolite LBQ657 through esterase hydrolysis

  • Protein-binding: High

  • Elimination: Renal and fecal pathways

  • Half-life: Approx. 9–11 hours

  • Efficacy: Reduces heart failure hospitalizations and mortality in HFrEF patients.

• Metoprolol Succinate (Toprol XL)

  • Class: Selective β₁-adrenergic blocker

  • Pharmacodynamics:

  • Decreases myocardial oxygen demand and heart rate

  • Reduces renin release

  • Improves left ventricular filling

  • Pharmacokinetics:

  • Metabolism: Primarily via CYP2D6

  • Half-life: 3–7 hours

  • Excretion: Renal (inactive metabolites)

  • Consideration: Preferred over carvedilol due to being cardioselective; less likely to cause bronchospasm in COPD patients.

• Dapagliflozin (Farxiga)

  • Class: SGLT2 inhibitor

  • Pharmacodynamics:

  • Blocks glucose reabsorption in proximal renal tubule

  • Leads to:

    • Glycosuria

    • Mild osmotic diuresis

    • Blood pressure reduction

  • Improves heart failure outcomes by reducing:

    • Hospitalizations

    • Cardiovascular death (supported by DAPA-HF trial)

  • Pharmacokinetics:

  • Absorption: Rapid, peak plasma concentration within two hours

  • Metabolism: Primarily via UGT1A9 conjugation

  • Half-life: Approx. 12 hours

  • Excretion: Urine and feces

• Warfarin (Coumadin)

  • Class: Anticoagulant

  • Pharmacodynamics:

  • Inhibits vitamin K epoxide reductase complex, reducing synthesis of clotting factors II, VII, IX, X, proteins C & S

  • Pharmacokinetics:

  • Complete oral absorption

  • Protein-binding: 99%

  • Metabolism: Hepatic CYP2C9

  • Half-life: 36–42 hours

  • Monitoring: Essential due to narrow therapeutic window and numerous interactions.

• Furosemide (Lasix)

  • Class: Loop diuretic

  • Pharmacodynamics:

  • Inhibits Na⁺-K⁺-2Cl⁻ symporter in thick ascending loop of Henle

  • Leads to potent natriuresis and diuresis

  • Pharmacokinetics:

  • Absorption: Rapid

  • Bioavailability: 60–70%

  • Onset: 30–60 minutes

  • Half-life: Approx. two hours; prolonged in renal impairment

Medications Discontinued:

• Valsartan: Stopped to avoid duplication and overlap with Entresto; a 36-hour washout period is required to prevent hypotension and hyperkalemia.

• Potassium Chloride: Discontinued due to hyperkalemia risk with Entresto.

• Carvedilol: Replaced with metoprolol succinate due to COPD exacerbation risk.

• Pioglitazone: Discontinued due to fluid retention and contraindication in NYHA Class III–IV heart failure.

• Glimepiride: Stopped over hypoglycemia and weight gain risks; replaced by dapagliflozin.

2. Monitoring Parameters for Each Medication

• Sacubitril/Valsartan (Entresto)

  • Therapeutic Monitoring:

  • Assess symptoms: Improved dyspnea, decreased orthopnea, reduced edema, weight loss

  • Monitor BNP trends and heart failure hospitalization rates

  • Blood pressure for hypotension/orthostasis

  • Labs for potassium levels and serum creatinine

  • Watch for signs of angioedema (swelling of face, neck, or throat)

  • Adverse Effects Monitoring:

  • Avoid combining with ACE inhibitors.

• Metoprolol Succinate (Toprol XL)

  • Therapeutic Monitoring:

  • Target resting heart rate: 50–70 bpm

  • Monitor symptoms improvement within weeks/months

  • Long-term evaluation of ejection fraction

  • Adverse Effects Monitoring:

  • Regular blood pressure checks to prevent hypotension

  • Monitor for bradycardia and signs of worsening heart failure (weight gain, edema, jugular venous distention)

  • Awareness of bronchospasm, particularly in COPD patients

  • Education on hypoglycemia signs (metoprolol can mask symptoms)

• Dapagliflozin (Farxiga)

  • Therapeutic Indicators:

  • Monitor symptoms reduction, hospitalizations, weight loss

  • Blood glucose and A1c levels

  • Blood pressure trends to assess hypotension risk

  • Adverse Effects Monitoring:

  • Assess renal function via serum creatinine and eGFR routinely

• Warfarin (Coumadin)

  • Therapeutic Monitoring:

  • Target INR: 2.0–3.0 for non-valvular atrial fibrillation

  • Frequent INR monitoring to prevent thromboembolic events

  • Adverse Effects Monitoring:

  • Monitor for signs of bleeding (gums, nose, urine, stool)

  • Complete blood count for hemoglobin and hematocrit tracking

  • Educate on food interactions; maintain consistent Vitamin K intake.

3. Potential Drug Interactions

• Sacubitril/Valsartan (Entresto):

  • Should not be co-administered with ACE inhibitors, potassium supplements, or potassium-sparing agents to avoid hyperkalemia and renal dysfunction.

  • NSAIDs may impair renal perfusion and increase hypotensive effects with diuretics.

  • Maintain low-sodium diet for therapeutic benefit; no significant food interactions.

• Metoprolol Succinate (Toprol XL):

  • May antagonize bronchodilators (e.g., albuterol) effect, worsening COPD symptoms.

  • Risk of bradycardia and hypotension when combined with other antihypertensive agents, including Entresto.

• Dapagliflozin (Farxiga):

  • Combined use with diuretics or Entresto can cause volume depletion.

  • Monitor renal function over concurrent RAAS blockade scenarios.

• Warfarin (Coumadin):

  • Co-administration with atorvastatin increases bleeding risk via CYP3A4 inhibition.

  • Aspirin potentiates anticoagulant effects; increased bleeding risk.

  • Dietary Vitamin K intake must be consistent. Alcohol can also enhance bleeding propensity.

• Furosemide (Lasix):

  • Initially used for volume overload; can interact with Entresto and dapagliflozin, leading to dehydration.

  • Monitor sodium intake to avoid excessive diuresis and electrolyte fluctuations.

4. Patient Counseling and Lifestyle Modifications

• Educate the patient about the new medication regimen, focusing on:

  • Adverse effects prevention

  • Monitoring for drug interactions and adherence strategies

  • Importance of hydration and diet (low-potassium, consistent Vitamin K intake)

  • Tools for adherence: Pill organizers, charts, and reminders

Specific Counseling Points:

• Sacubitril/Valsartan:

  • Monitor blood pressure and BNP, potassium, creatinine levels regularly.

  • Watch for angioedema symptoms (swelling of face, etc.) and avoid salt substitutes.

  • Daily weights recording to track fluid retention; rise slowly to avoid dizziness.

• Metoprolol Succinate:

  • Closely track blood pressure; identify signs like bradycardia or symptoms of heart failure worsening.

  • Recognize hypoglycemia symptoms due to masking by metoprolol.

• Dapagliflozin:

  • Routine renal function checks; ensure proper hydration.

  • Recognize urinary and genital infections signs, report promptly.

• Warfarin:

  • INR and CBC monitoring; report any unusual bleeding signs immediately.

  • Follow a consistent Vitamin K diet; avoid drastic changes in intake of Vitamin K-rich foods.

Lifestyle Modifications:

• Record daily weights and manage sodium intake to avoid fluid accumulation.

• Moderate physical activity, smoking cessation, and limit alcohol consumption.