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Hey what’s up guys today we’re gonna be talking about medications that specifically lower mortality in congestive heart failure but specifically we’re gonna be touching on two new medications that aren’t really talked about all that much in the guidelines because they’ve been recently approved and they’ve been proven to reduce mortality and after all we give
Medications to patients with heart failure because we want to improve patient outcomes we want to decrease time spent in the hospital but aside from that we want to make sure that these patients live longer morbidity means decreased time in the hospital mortality means it improves their lifespan so let’s very quickly recap what medications have been given in the
Past with a proven mortality now very quickly diastolic dysfunction right so we can separate heart failure into diastolic dysfunction and systolic dysfunction systolic dysfunction means that ejection fraction is reduced the amount of blood that pumps out of the heart isn’t normal diastolic means we have a preserved ejection fraction so in diastolic dysfunction
We actually don’t have any medications that improve mortality outcomes or decrease mortality i should say so all of the medications in diastolic dysfunction are geared more towards symptomatic control and/or comorbid conditions such as hypertension hyperlipidemia atrial fibrillation things of that nature systolic dysfunction is a little bit different we do have
Medications that reduce mortality the main classes of drugs here going to be beta blockers and ace inhibitors and or the arb now beta blockers is does not have a class effect meaning there are only three medications in the beta blocker class that reduce mortality this is miss oprah law car beta law and metoprolol sussan a bee’s three medications are important to
Note atenolol does not reduce mortality you have to do the saw prologue metoprolol carvedilol ace inhibitors or arbs on the other hand is a class effect this means that it doesn’t matter which one you choose whether it’s enalopril lisinopril they’re going to reduce mortality and you never want to combine an ace or an arb now we also have the spray no lactone and
A player known these are medications that are going to be given in class 3 or class for congestive heart failure you’re not going to use both of them spratt a lactone and a plural are used as one in the same the difference is a player known has less endocrine side effects other medications that are commonly used in the treatment of heart failure are going to be
Diuretics and digoxin now diuretics do not reduce mortality they are simply there to relieve symptoms of fluid overload digoxin again although it does decrease the amount of time in the hospital it does not decrease mortality it is going to improve symptoms such as shortness of breath it’s going to affect contractility of the heart so the dachshund does not improve
Mortality so really the main medications here are gonna be beta blockers ace inhibitors at player known and/or soprano lactone now the two new medications that we’re gonna be talking about today are going to be a vibrating and tsukuba trill now tsukuba trill is going to be a combination drug with valsartan and we’ll get into the specifics in just a second so let’s
Start off with afib reading all right moving on to our starting with of everdene now whatever burning does it’s going to affect the sa node so it’s really targeting the sa node it’s prolonging the the polar ation phase and ultimately what we’re doing is we’re slowing down the heart increasing the amount of time the heart has to fill with blood and essentially
Providing a similar benefit to that as a beta blocker now it you have to be aware this is not a substitute for a beta blocker so in order to be a candidate for a vivir d we have to have an ejection fraction less than 35% we have to beyond the maximum tolerated dose of the beta blocker like i said this is not a substitute and or maybe there’s a contraindication to
Evade a blocker which is why we’re going to be then using of everdene we also have to be in normal sinus rhythm and we have to have a heart rate of at least 70 beats per minute because this is going to affect the sa node it’s going to decrease the amount of times that the heart pumps so if we already have you know a rate of 70 beats per minute or 60 beats per minute
We don’t want that falling a bit lower so minimum of 70 beats per minute on the side the heart rate cannot be controlled by a pacemaker so we have to have sinus rhythm ejection fraction less than 35% maximum tolerated dose on a beta blocker in normal sinus rhythm with a heart beat of at least 70 beats per minute these patients are candidates for liberty moving on
To contraindications for of everdene now we have to keep in mind this is going to be only used in stable consistent failure this means one of the contraindications here is acute exacerbation of chf we do not start this medication when we have acute exacerbation another contraindication is going to be hypotension which is defined as a systolic of 90 and a diastolic
Of 50 sa dysfunction as say no dysfunction a severe hepatic impairment and or if the patient is taking a strong cyp 3 for a inhibitor now all of this data is really coming from the shift’ trial the schiff trial had 6,000 558 patients they were then divided half were given placebo and half were given of libertines they were then followed for a period of about two
Years after the two years they noticed that the patients that were taking a vivir deen had decreased hospital admissions and overall there were a decreased number of deaths and this is where the evidence comes for a vivir dean now again remember in order to be a candidate for everybody before starting therapy patients have to be on the maximum tolerated dose of
A beta blocker they should also be on a maximum tolerated dose per guidelines of an ace inhibitor now if the patient has a contraindication to a beta blocker they should be started on an ace inhibitor first and then started on a vibrating moving on to the dosing of a viper dean now we’re really going to start the medication at 5 milligrams twice a day with food
Those patients that are at high risk for having conduction disturbances should have this those cut in half meaning we do two and a half milligrams twice daily now every two to four weeks we’re going to titrate upwards until we get a maximum dose of seven and a half milligrams twice a day we want to either stop medication or reduce the amount of medication given if
We get a heartbeat of 50 beats per minute or less or if we’re having signs and symptoms of bradycardia if we’re at two and a half milligrams twice a day it’s the initial starting dose we’re already having a heartbeat of less than 50 over having signed in the symptoms of bradycardia then we’re gonna stop the medication altogether adverse reactions now like we said
This is going to affect the sa node so one of the adverse reactions here is going to be bradycardia now unlike a beta blocker this is going to have an increased risk for causing hypertension not hypotension we also have to be on the lookout for our block and atrial fibrillation moving on to tsukuba trail now like we said tsukuba trail is going to be combined
With valsartan which is an art some quick background information before getting into the specifics ace inhibitors and arbs are going to be responsible for affecting the renin-angiotensin-aldosterone system natura dick peptides are going to be released when we have increased myocardial filling pressures with these natural reddick peptides do is they’re going to
Reduce the amount of rent and release by the kidneys they’re going to increase the gfr they’re going to cause vasodilation in in essence natura attak peptides are good all right so let’s talk about nefra lisen now this medication tsukuba trill is a nefra lisent inhibitor knepper lisen is going to decrease the amount of natural peptide it’s going to break down
Angiotensin ii and it’s also going to decrease bradykinin levels so when we give tsukuba trill to snuff release an inhibitor it’s going to produce the opposite effect it’s gonna raise brady kind of levels and it’s gonna raise natural retic peptides because we have this increased brady kind of levels because it’s breaking down angiotensin ii this is why we need to
Combine it with the medication that affects the ross system the renin-angiotensin-aldosterone system this is why this medication is combined now initially the naturalised inhibitor was combined with an ace inhibitor they took this off the market the fda actually pulled this off the market because although it did improve outcomes there was a reduction in mortality
They noticed there was severe and jeolla-do because this ace inhibitor that was combined with the nefra lisent inhibitor actually affected three enzymes that were responsible for this effect now when we combine it with tsukuba trill and valsartan valsartan being an arb it’s only affecting one enzyme so in essence this new combination drug of tsukuba trail which
Is the naturalised inhibitor valsartan which is the arb is going to only affect one enzyme out of the three that the original medication affected one enzyme responsible for brady kind and aggregation so overall this medication is going to block the renin-angiotensin-aldosterone system it’s going to reduce the amount of risk for angioedema and it’s going to raise
Natural retik peptides now this combination drug like we said is an arb and it’s a natural lisen inhibitor this means that we should not combine this medication with any other arb and we should not combine this medication with any other ace inhibitor now what’s not so clear is when to use the medication first-line now we are we do know who it’s indicated for this
Is indicated for the chf patient that has class two class three or class four chf we’re not so sure if we should use this combination drug in place of the ace inhibitor first-line therapy or if we should use this combination drug instead of the arb mono therapy if for whatever reason we cannot use an ace inhibitor universally there are some exceptions where this
Might be indicated first-line so if the patient can’t tolerate the ace inhibitor for whatever reason we do know that this combination drug is better than arb mono therapy when we have increased bnp levels we have a systolic blood pressure over a hundred and we have a gfr over 30 this combination drug is better than our mono therapy now to dose this medication we’re
Really going to be starting at a dose of 49 over 51 twice a day we’re gonna then titrate again every in about two to four weeks to reach the maximum dose and if we have severe renal impairment then we’re going to start the titration or we start the initial dose at half the recommended dose so half of 49 milligrams over 51 milligrams for the combination drug now
All of this evidence and all of these guidelines are really coming from the paradigm h-f trial this trial had eight thousand four hundred and forty two patients who had an ejection fraction less than 40 percent and who had chf class two three or four these patients were then split half received an ala krell ten milligrams twice a day the other half received the
Combination drug they were then followed for about two years and after the two years we realized that the patient’s receiving the combination medication actually had decreased all cause of mortality and had fewer hospital admissions so this is why or this is where all of the evidence comes from the paradigm h f trial now contraindications to the combination drug
Abouts are tent and tsukuba trail are gonna be the same as any other ace and arb contraindication we’re gonna want to avoid this in pregnancy because it can have teratogenic effects we’re also gonna want to avoid this in patients who have prior severe angioedema because all of the risk is low it’s silly life-threatening events we’re also gonna want to avoid this
In patients who are breastfeeding and we’re gonna want to avoid this in patients with severe hepatic impairment adverse reactions for this combination drug of tsukuba trail and valsartan are gonna be hyperkalemia hypotension cough dizziness and even renal failure angioedema is also a risk here it’s going to be low but again this is going to be a life-threatening
Event so we still have to be aware of its presence so that concludes today’s talk we talked about ivabradine we talked about tsukuba trail which is essentially a combination drug with valsartan these both reduce mortality naik we set these drugs are only reducing mortality in patients with systolic chf with systolic dysfunction we do not have any proven therapies
That reduce the mortality in diastolic dysfunction heart failure
Transcribed from video
CHF Mortality Reduction: Ivabradine and Sacubitril-Valsartan By Medgeeks
