Interpreting labs after neprilysin inhibitor treatment

Doctors often ask themselves—should I still measure the BNP in patients on ARNIs, if its elevation does not necessarily reflect muscle damage? Or, should I be measuring NT-proBNP instead? In this video, from our Cardiology Lab Essentials course, you'll find out how neprilysin inhibitor treatment affects the measurement and interpretation of natriuretic peptides, and what you can do to avoid lab result misinterpretation.

Master the ins-and-outs of cardiology lab testing with our Cardiology Lab Essentials course. You'll take a deep dive into the lab tests requested for common cardiology conditions, when to request them, how to interpret the results, and much more!

[00:00:00] In heart failure treatment, the key strategy is the blockade of the renin-angiotensin aldosterone system or RAAS, in order to decrease blood volume and to counteract vasoconstriction. Further tactics focus on supporting the system, which counteracts this system, namely natriuretic peptides like BNP. This has been attempted in two distinct ways.

[00:00:30] The first approach was to supplement BNP with the synthetically produced BNP compound, named nesiritide. Intravenous administration of nesiritide should actively induce diuresis, natriuresis, and vasodilation just like the endogenous BNP does. The second approach aims at increasing BNP by inhibiting BNP breakdown. For this purpose, a new class of drugs has been

[00:01:00] established that inhibit neprilysin, which is the enzyme responsible for BNP degradation. Neprilysin inhibitors were then successfully combined with angiotensin receptor blockers. This class of drugs is abbreviated ARNI. ARNIs have been shown to be superior to ACE inhibitors or monotherapy with angiotensin receptor blockers, in chronic heart failure patients with reduced ventricular function. Therefore, ARNIs are the recommended drug therapy of choice in these patients.

[00:01:30] However, it's important to know that the use of this compound is contraindicated in patients with a history of angioedema, as this is a rare side effect of neprilysin inhibitors. Since these drugs interfere with natriuretic peptides in the body, how do they affect lab results from BNP and NT-proBNP testing? The administration of the synthetic BNP, nesiritide, naturally leads to an increase in BNP in the plasma, which can be detected in lab. Obviously, this

[00:02:00] elevation is artificial and does not reflect actual heart damage. NT-proBNP levels, on the other hand, are not affected since nesiritide does not contain NT-proBNP. What about ARNIs? Since ARNIs inhibit the degradation of BNP, endogenous BNP is naturally elevated in patients taking these drugs. Again, the elevation does not reflect heart muscle damage. On the other hand, neprilysin does not degrade [00:02:30] NT-proBNP so ARNI treatment does not affect NT-proBNP levels in the blood. This means that increased NT-proBNP levels in patients on ARNIs do indicate heart muscle damage. A lot of doctors now ask themselves, should I still measure BNP in patients on ARNIs, if its elevation does not reflect disease progression? Or should I switch to NT-proBNP instead? Experts still advice that BNP measurements can be used to diagnose

[00:03:00] heart failure in patients on ARNIs. Drug-induced BNP elevations are rather modest so they needn’t compromise the ability to rule out heart failure, which is still the main use of BNP testing, nor do they significantly impact the ability to rule in heart failure in most patients. The use of BNP for therapy guidance is not fully evaluated yet in patients taking these medications. However, experts advise to wait one month after starting ARNIs until BNP has reached a new steady

[00:03:30] state and then repeat BNP testing to establish a new baseline value for further monitoring. In addition to BNP, NT-proBNP is a good lab marker to diagnose heart failure as well as to monitor heart failure patients. The concept, the lower the NT-proBNP results the better, is applicable for all patients whether on ARNIs or not. So, if your patient is on either ARNI or nesiritide, be aware that

[00:04:00] BNP plasma levels will be falsely elevated and these lab results may not reflect your patient's heart condition.