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Difficulty: HardPharmacologic Interventions

A female patient, aged 64, is evaluated in the ambulatory clinic for ongoing exertional dyspnea. She was diagnosed with heart failure with reduced ejection fraction two years ago following an anterior myocardial infarction. Current symptoms include shortness of breath when walking up a single flight of stairs, consistent with New York Heart Association class II symptoms. Her medical history includes type 2 diabetes mellitus and hypertension.

Current medications are lisinopril, metoprolol succinate, empagliflozin, and torsemide as needed.

Vital signs show a blood pressure of 118/76118/76 mm Hg and a heart rate of 6868/min. Physical examination reveals a normal jugular venous pressure, clear lungs, and trace bilateral pedal edema.

Recent laboratory studies:
Sodium: 138138 mEq/L
Potassium: 4.54.5 mEq/L
Creatinine: 1.11.1 mg/dL (baseline 1.01.0 mg/dL)

An echocardiogram from one month ago shows a left ventricular ejection fraction of 32%32\%.

The physician plans to transition the patient from her current angiotensin-converting enzyme inhibitor to sacubitril-valsartan to further reduce the risk of cardiovascular mortality and heart failure hospitalization.

Which of the following is the most appropriate step in implementing this pharmacologic intervention?

  1. Discontinue lisinopril and initiate sacubitril-valsartan after a 36-hour washout periodAnswer
  2. B
    Maintain lisinopril at the current dose and add sacubitril-valsartan to maximize neurohormonal blockade
  3. C
    Cross-taper the medications by halving the lisinopril dose for three days while starting sacubitril-valsartan
  4. D
    Measure baseline serum B-type natriuretic peptide levels and use them to guide dose titration of the new agent
  5. E
    Order a renal artery duplex ultrasound prior to initiation to rule out bilateral renal artery stenosis

Answer

Discontinue lisinopril and initiate sacubitril-valsartan after a 36-hour washout period.
The correct approach when switching a patient from an angiotensin-converting enzyme (ACE) inhibitor (like lisinopril) to an angiotensin receptor-neprilysin inhibitor (ARNI) (like sacubitril-valsartan) is to enforce a strict 36-hour washout period. Both ACE and neprilysin are enzymes responsible for the degradation of bradykinin. Simultaneous inhibition of both pathways significantly increases bradykinin levels, which can precipitate life-threatening angioedema. The 36-hour window ensures adequate clearance of the ACE inhibitor before neprilysin inhibition begins. Note that this washout period is not required when transitioning from an angiotensin receptor blocker (ARB) to an ARNI.

Step-by-Step Solution

1
Identify the indication for the pharmacologic change
The patient has symptomatic HFrEF (NYHA class II, LVEF 32%) on optimal medical therapy including an ACE inhibitor, beta-blocker, and SGLT2 inhibitor. Upgrading the ACE inhibitor to an ARNI (sacubitril-valsartan) is guideline-directed.
ARNIs provide superior reduction in morbidity and mortality compared to ACE inhibitors in patients with chronic symptomatic HFrEF.
2
Determine the specific pharmacokinetic and pharmacodynamic requirements for initiating an ARNI
Sacubitril-valsartan cannot be administered concurrently with an ACE inhibitor due to a synergistic accumulation of bradykinin.
ACE breaks down bradykinin, and neprilysin also breaks down bradykinin. Inhibiting both simultaneously severely increases the risk of angioedema.
3
Establish the correct protocol for transitioning medications
A minimum 36-hour washout period is required after the last dose of the ACE inhibitor before the first dose of the ARNI can be administered.
This specific timeframe allows for adequate clearance of the ACE inhibitor, mitigating the interaction and safely facilitating the transition.

Key Concept

When transitioning a patient with heart failure from an angiotensin-converting enzyme (ACE) inhibitor to an angiotensin receptor-neprilysin inhibitor (ARNI), a strict 36-hour washout period is required to minimize the risk of angioedema.
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Pharmacologic Interventions

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