The video version of this podcast can be found here:

·      https://youtu.be/30qLbVnKHW8

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode I give a brief overview of the mechanism of action of sacubitril valsartan for heart failure.

The NICE guidance on Chronic Heart Failure is covered in these episodes:

Part 1- Diagnosis: https://youtu.be/hjKE4JAQM6c

Part 2 – Drug management: https://youtu.be/UGD7-osSlv0

Part 3 – Additional management: https://youtu.be/i0L-Nv4bJzs

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

Disclaimer:

The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release] 

• Music provided by Audio Library Plus 
• Watch: https://youtu.be/aBGk6aJM3IU 
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There is a podcast version of this and other videos that you can access here:

Primary Care guidelines podcast:

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148

There is a YouTube version of this and other videos that you can access here: 

• The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk

The NICE guideline on Chronic heart failure in adults: diagnosis and management [NG106] can be found here: 

·      https://www.nice.org.uk/guidance/ng106

Additional information on ARNIs can be found here:

·      https://www.ncbi.nlm.nih.gov/books/NBK507904/#:~:text=Mechanism%20of%20Action,-The%20pathophysiology%20of&text=Valsartan%20is%20an%20angiotensin%20receptor,neprilysin%20will%20accumulate%20angiotensin%20II

Transcript

Hello and welcome! I’m Fernando, a GP in the UK.

What are Angiotensin receptor–neprilysin inhibitors? They are a relatively new class of medications used specifically in the management of heart failure with reduced ejection fraction. At present, the only available one is sacubitril/valsartan.

If you are interested in learning how Sacubitril/valsartan works, here is some background information.

The first thing to understand is that the pathophysiology of heart failure involves an abnormal activation of the renin-angiotensin-aldosterone system (RAAS). This leads to vasoconstriction, hypertension, increased aldosterone levels, increased sympathetic tone, and eventually, cardiac remodelling, all of which worsen the disease over time. ACEIs or ARBs play a major role in reducing HF morbidity and mortality by blocking this abnormal activation

At the same time that the renin-angiotensin-aldosterone system is activated, the natriuretic peptide system is also activated, hence the elevated BNP and NT-pro BNP seen in heart failure. This compensatory mechanism leads to vasodilation, natriuresis, and diuresis. As a result, the natriuretic peptide system decreases blood pressure, lowers the sympathetic tone, and reduces aldosterone levels. The natriuretic peptide system functions antagonistically to the renin-angiotensin-aldosterone system and has favourable impact on heart failure. Natriuretic peptides are broken down by an enzyme called neprilysin.

Sacubitril/valsartan is a combination product. Sacubitril is a pro-drug that, upon activation, acts as a neprilysin inhibitor. So, it works by blocking the action of neprilysin, thus preventing the breakdown of natriuretic peptides, which leads to a prolonged duration of the favourable effects of these peptides.

However, because neprilysin also breaks down angiotensin II, inhibiting neprilysin will accumulate angiotensin II. For this reason, a neprilysin inhibitor cannot be used alone; it must always be combined with an ARB to block the effect of the excess angiotensin II. This is why Valsartan is used.

Another important substance broken down by neprilysin is bradykinin; neprilysin inhibition will also cause a build-up of bradykinin. Therefore, sacubitril cannot be used with an ACEI due to an increased risk of angioedema if both these drugs are combines or given in a short timeframe. And this is why when switching between ACEI and sacubitril/valsartan, the patient must undergo a 36-hour washout period to lower the risk of angioedema.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.