Sheryl Chow, PharmD, BCPS; Akshay Desai, MD; Peter L. Salgo, MD; Scott Solomon, MD, discuss the mechanism of action for angiotensin receptor neprilysin inhibition in the management of chronic heart failure and review the evidence with sacubitril/valsartan.
What about be angiotensin receptor net for licen inhibitors our knees that’s another class of drugs we’re getting into some strange territory around here cheryl i’m going back to you what are they and and when do they get used right well i mean maybe i actually want to refer to the scot on this because he’s done extensive studies on the this our knee in particular
So i don’t want to steal scott’s thunder no no feel free but you probably do much better than an angiotensin receptor knepper lisen inhibitor so it’s a new class of drugs of course there’s only one drug so far in that class and it’s tsukuba trill valsartan a tsukuba traval sartain is essentially a compound that contains both pal sartain which is an angiotensin
Receptor blocker we know it well blocks the eighty one receptor and tsukuba trill which is a prodrug nebulizing inhibitor they’re together in a crystal essentially okay you ingest it and these come apart into the component parts so the eighty one receptor blocks the the arb blocks the 18 one receptor and tsukuba trill is then converted esterified to tsukuba trail
Lat which is the active form and that inhibits knepper licen what is knepper licen knepper licen is a ubiquitous enzyme that is responsible for the breakdown of a number of vasoactive peptides including the biologically active natural retic peptides like anp bnp and cnp so we were talking before about bmp as a marker and now we remember that bmp is also a hormone
That is as cheryl said very early in the program goes up when in the setting of heart failure and it goes up as a compensation so what happens is that when you give an emperor licen inhibitor you both block the ring and angiotensin system and you make natural retic peptides go up okay and so you’re doing two things at once do you remove the usefulness of bmp as
A marker at the same time as you’re modifying it because you were a therapeutic effect turn turns out you do because because bmp goes up when you give an f or licen inhibitor it’s no longer gonna be as good a marker of the severity of heart failure it’s gonna be confusing because if you start a patient on this drug bmp you’ll go up but remember before we talked
About nt probiem p nt probe e&p is not a substrate for an emperor lisen and so it’s still a really good marker of a severity of heart failure even in the setting of nipple ison innovation okay but just also to clarify that scott i don’t think you’re suggesting that hospitals that use b and p should switch over to nt pro pnp because of the effect of this rt
I might be i mean i’m if you’re going to use nrt and you’re going to want to follow some metric that you can measure in the blood it’s gonna be very very difficult to follow bmp okay let’s looks like some of the research that’s out there on these are knees and head to head studies there’s the paradigm h f trial right which was a head-to-head trial with an arnie
Which is saku betrayal of else are ten versus the ace inhibitor in alec realm and what did it show what were the implications so paradigm hf was the largest heart failure trial that we’ve ever done so far eighty five hundred patients randomized to either this arnie tsukuba traverse arden or enalapril which is considered has been considered the gold standard
Of treatment and heart failure and paradigm was actually stopped early by the data safety monitoring board for overwhelming efficacy because there was a 20% reduction in a composite endpoint of cardiovascular death and heart failure hospitalization a 20% reduction in cardiovascular death alone a 16% reduction in all cause mortality all of these were highly
Statistically significant important study about 30 day readmissions study comparing tsukuba trail valsartan vs. in ellebra i’m gonna ask my colleague dr. decide him tell you about that because he did study readmissions are a big problem in heart failure i think we’re all concerned that patients who leave the hospital come back and because medicare has now set
Penalties that for hospitals with higher than expected 30-day readmission rates this is a target so when we looked at this in the paradigm hf study and looked at patients allocated to the tsukuba trial valsartan versus those with enalopril after their first hospitalization during the trial and then asked the question how many of them were readmitted in 30 days
And then beyond and it turns out that the rates of 30-day readmission amongst this in cuba travel are defeated patients after a first heart failure hospitalization are lower by a substantial amount by by 20% and then in patients who were treated with an hour maybe 20% a big number yeah you get 20% that’s verified just distally significant just kind of perk up
That’s an impressive result and there’s results of post hoc analysis of paradigm hf with diabetes patients – yeah yes i think that what we know is a couple of things about diabetes one is that diabetics benefit equally from from non diabetics with therapy with tsukuba trail valsartan and there are consistent benefits and that’s important because a large fraction
Of our heart failure with reduced ejection fraction patients are diabetic but the other is this interesting observation from the trial which is that the although the rates of new onset diabetes were not changed by treatment with tsukuba tro valsartan in preference to enalapril the glycemic control was better in the patients treated with tsukuba trail valsartan
Than an ala per link and he before met anyone sea levels were actually lowers i know we’re on the clock but i have got to ask why well let’s gotta answer that he’s this morning you know you know that it’s not completely clear but it turns out that stimulation of the natural retic peptide system okay may actually play a role in glycemic control and very interestingly
Glp-1 glucagon-like peptide one which we actually stimulate as a way to control blood sugars and in patients is a substrate for knepper licensed so if you give a knepper lisen inhibitor that can actually go up and that might be good so it’s got a we we’re not entirely sure why we you know this is a post hoc finding so i wouldn’t want to make too much of it but
It says that if you’re have a patient who has diabetes and heart failure that this therapy is certainly not going to make the diabetes worse and it may improve glycemic control we had a 30% reduction in use of new use of insulin in diabetic patients this is ridiculously interesting and i’m sure that there’s another textbook coming on all of this as we go forward
But if you can make the diabetes better and simultaneously treat heart failure that’s that’s a that’s a massive win it seems to me if it holds up going forward well it’s important to remember that a diabetic patient with heart failure has about twice the risk of a non diabetic patient so anything we can do to improve both the heart failure substrate and also the
Metabolic substrate would would be useful you
Transcribed from video
Angiotensin Receptor Neprilysin Inhibition in Heart Failure By HCPLive
