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PARADIGM- HF trial/Entresto

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The guidelines for the management of heart failure were updated in 2016 one of their new recommendations so that for patients who are currently tolerating an asian arm that they could be switched to this new medication called entresto and it would provide further mortality benefit so let’s look through the paradigm hf trial and see how they came up with this

Recommendation so first off what is interested it is a combination product of valsartan and tsukuba troll and it’s not just your standard combination it’s actually a fused molecule or a co crystallized molecule and so they give it a new term they call it an arnie which is how its represented in a guideline which is an angiotensin receptor and a pearlized

And inhibitor so we’re familiar with cell sartain which is going to block the rat system but tsukuba trial which is the napper liason inhibitor blocks that ends on matt burleson which is responsible for the breakdown of bmp breaking amyloid beta peptide and other vasoactive peptides so when you inhibit that breakdown you allow the veldt starting to work more

Effectively so i include the reference for the paradigm hf trial at the top here make sure as always go look this up and actually read to the trial around i have the pubmed id on that for you as well but just as a very very brief summary the trial was the multicenter randomized comparative trial there was over 8,000 people in the trial and it looked at interested

With 200 milligrams or valsartan tsukuba draw twice daily versus now a 10 milligrams twice daily and their primary outcome was a composite of cardiovascular mortality or hospitalization due to heart failure some of the inclusion exclusion criteria so the inclusion criteria patients had to have pet breath with injection fraction less than 35% they had to be

On an ace or arb for at least four weeks to the study they also had to be in a beta-blocker for at least four weeks some of the exclusion was it systolic blood pressure less than 100 estimated gfr of less than 30 and patients could not be enrolled in study if they ever had a history of angioedema so here’s some of the results that were reported and there’s

Others as well but these the ones i want to focus on so for the composite you see a number needed to treat of 21 so for every 21 patients that we treat with entresto as opposed to an outgrow we’re going to stop 1 extra cases of cardiovascular deaths or hospitalization due to heart failure and then when we look at the components by themselves we still get pretty

Significant differences clinically speaking so cardiovascular mortality number needed to treat was 31 and hospitalization number the entry was 36 adverse effects were pretty similar the ones that stood out so symptomatic hypertension was more prevalent in the entresto group so in this case number mewtwo horn was 21 so patients that are uninterested definitely

Need to be monitoring their blood pressure on a daily basis and there were some patients who even got to a systolic blood pressure of less than 90 and in this case number neither harm was 77 potassium was also monitored and patients who reached a level of 6 or more were included in this year and it wasn’t significant difference but it was trending to be forced

In the enalapril group so that’s one extra benefit for our interest of if you have a patient who is starting entresto and are currently taking an eighth and editor make sure that they stop the ace for at least 36 hours prior to starting the interests oh so it’s a qubit oral component of interest that increases someone’s risk for angioedema and so we take that

Along with an 8 that risk goes up even more so i’ve actually seen this happen firsthand a patient was given samples of entresto wasn’t aware that he was supposed to stop his ace and editor took them together and end up in the hospital with angioedema and technically speaking because he has a history now of angioedema he’s no longer a candidate for entrust oh and

So he may have missed out on an opportunity for a good medication because of a failure to console so something to keep in mind always always always make sure we’re talking to people about this 36 hour washout between ace and he started in trust up typical starting doses 100 milligrams twice a day charging two to four weeks or so in increments and with the goal

Dose being 200 milligrams twice a day bmp should no longer be monitored so bmp is broken down by napper liason so if we inhibit that enzyme obviously bmp is going to go up so that’s no longer going to give us an accurate clinical picture if you want something similar just draw probiem p instead and that will be affected some long-term concerns that we have one

Is age-related macular degeneration and the other is alzheimer’s disease so that amyloid beta peptide that are normally broken down by nappa liason once that’s inhibited that breakdown and in theory kids start accumulating and forming the amyloid plaques that are concerned with alzheimer’s so this is something that our monitoring very closely and only time will

Tell to see if it’s an actual concern or not as far as macular degeneration if the patient comes and is very concerned about this or they have a family history of macular degeneration you could always recommend one of the different brands of eye lemons that contain the a red tube formula which is a lutein and zeaxanthin i made was to trial we know that there was

A little bit of benefit when taking that combination in the reduction as the development of macular degeneration i don’t have any evidence whatsoever to back that up as far as whether or not that would be significant for patients taking interest though and whether or not that would help but it probably won’t hurt it may be an option to try and certain patients

Just to keep that in mind let me know if you have any questions concerns i’d love to hear your comments and what you think about the trial feel free to post them thanks for watching

Transcribed from video
PARADIGM- HF trial/Entresto By CorConsult Rx Evidence-Based Medicine