[HN Gopher] EpiPen For Heart Attacks? Idorsia Launches Phase III...
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       EpiPen For Heart Attacks? Idorsia Launches Phase III Study Of
       Selatogrel (2021)
        
       Author : bookofjoe
       Score  : 86 points
       Date   : 2024-03-28 12:27 UTC (10 hours ago)
        
 (HTM) web link (scrip.citeline.com)
 (TXT) w3m dump (scrip.citeline.com)
        
       | jdawg777 wrote:
       | > will be supplied with an auto-injector, containing either 16mg
       | of selatogrel or a placebo liquid formulation.
       | 
       | Its unfortunate that half the trial patients are getting a
       | placebo, especially when it is life or death, but I suppose
       | that's how drug trials work.
        
         | crubier wrote:
         | This is how all drug trial works.
         | 
         | And it regularly ends up being not-so-unfortunate, when the
         | drug turns out to have dangerous side effects that overshadow
         | its benefits.
        
           | throwup238 wrote:
           | Not all. The need for a placebo control is weighed against
           | ethics and whether a placebo is even realistic.
           | 
           | Chemotherapy drug trials often just use standard treatments
           | as a control group. They're likely using placebo here because
           | there's no other drug in its class yet. Normally emergency
           | life or death trials don't have placebos unless the treatment
           | is the first of its kind.
        
             | ano-ther wrote:
             | Yes. And placebo control is actually quite a weak standard
             | (= better than nothing). Ideally, there should be more
             | head-to-head studies.
             | 
             | Alas, they are also more likely to fail (and give the
             | competition data) so developers avoid them, at least for
             | the initial approval.
        
               | LorenPechtel wrote:
               | And it's something the FDA shouldn't be allowing.
               | 
               | You want to bring a new drug to market, you should be
               | required to demonstrate that it's not strictly inferior
               | to existing options in at least some patients. I'm fine
               | with a head-to-head that comes out a tie (competition is
               | good for the marketplace) and I'm fine with a drug that
               | only works in a subset if that subset can be identified.
               | And I'm fine with a drug that doesn't work as well but is
               | more tolerated. I'm not fine with a drug that loses in
               | all respects in a head-to-head.
        
         | stephencanon wrote:
         | The standard joke here is that the researcher objects to the
         | need for a trial, saying "that would be condemning half my
         | patients to death!" and a medical student asks "which half?"
        
         | bookofjoe wrote:
         | FWIW, often a trial is halted before being completed if
         | statistical analysis of the preliminary results definitively
         | indicate a positive outcome, or unexpected negative/life-
         | threatening side effects emerge at an unacceptably high
         | incidence.
         | 
         | If the trial is halted prematurely because the drug is deemed
         | effective, immediately all individuals who received placebo are
         | given the real thing. If the trial is completed and it shows
         | the drug is effective, all those who received placebo are given
         | the real thing.
         | 
         | Know also that all participants are paid for participating.
        
           | Temporary_31337 wrote:
           | So are they going to wait with their heart attack until trial
           | is over? Maybe read the article first? This makes sense for
           | long term medicine like diabetes drugs etc but this one is
           | for heart attack
        
             | bookofjoe wrote:
             | Yes. That is how clinical trials work. I have run many
             | clinical trials. I read the article twice before I
             | submitted it.
        
               | epcoa wrote:
               | I think the charitable interpretation of who you are
               | replying to is that it would be silly to give this drug
               | for an acute event to people that received control (a
               | life-long standard anti-platelet) weeks after they had an
               | MI event. You're not going to say, oh that guy that had a
               | heart attack and PCI 4 weeks ago who is on DAPT, oh now
               | we're going to give this drug, the horse has already left
               | the barn so to speak and the intervention is no longer
               | indicated. That's how I interpreted the point at least.
        
             | LorenPechtel wrote:
             | Suspect heart attack--you head to the hospital pronto. The
             | trial involves injecting the drug immediately, then going
             | to the hospital. The placebo arm gets exactly the same
             | treatment everyone would get now--rush to the hospital.
             | This drug is purely about trying to keep the heart alive
             | long enough to reach the hospital. A hospital with a cath
             | lab is a far better treatment than this drug--but you can't
             | put that in your pocket.
        
         | jprete wrote:
         | The alternative is to see later studies like [1], which finds
         | that several popular heart interventions don't actually improve
         | all-cause mortality in the population of "severe but stable"
         | heart disease patients.
         | 
         | If stents and coronary bypasses don't increase life expectancy
         | (or quality of life!) for that population, then a lot of people
         | from that population took the risks of major surgery for no
         | benefit.
         | 
         | [1] https://med.stanford.edu/news/all-news/2019/11/invasive-
         | hear...
        
         | sp332 wrote:
         | Off the top of my head, maybe the shock of being jabbed with a
         | needle would have an effect on people's symptoms that should be
         | controlled for.
        
           | bookofjoe wrote:
           | It IS controlled for: ALL participants get jabbed with a
           | needle.
        
             | sp332 wrote:
             | Right, that's why you need to load some needles with a
             | placebo.
        
               | bookofjoe wrote:
               | Participants receiving placebo get the placebo through a
               | needle.
        
               | sp332 wrote:
               | Yes. I'm in favor of this.
        
         | LorenPechtel wrote:
         | But you don't know if the new drug is going to be better or
         | worse. Sometimes the placebo arm has a better outcome than the
         | drug arm.
         | 
         | And, unfortunately, sometimes they really mess up the
         | statistics. Consider that huge trial from some years ago that
         | declared hormone replacement for menopause symptoms definitely
         | bad. No, despite the huge size of the study they made a
         | fundamental mistake in recruiting participants--all that study
         | actually proved is what was long known: fat women shouldn't be
         | on hormone replacement.
        
       | binarymax wrote:
       | Here's the ongoing trial info:
       | https://clinicaltrials.gov/study/NCT04957719
        
       | bedobi wrote:
       | pretty sure at least in Sweden they use EpiPens for a bunch of
       | stuff, including heart attacks already?
        
         | percutaneous wrote:
         | Ahh yes, nothing treats heart hypo perfusion quite like forcing
         | the heart into overdrive and massive vasoconstriction. Why is
         | the US so far behind on this???
         | 
         | Edit: sorry I was getting technical. Yes it absolutely has a
         | role in cardiac arrest and it's used for this the world over.
         | 
         | It would be very detrimental in a patient with a heart attack
         | without arrest though due to increasing cardiac demand when
         | cardiac supply is already highly limited
        
           | ejstronge wrote:
           | > Ahh yes, nothing treats heart hypo perfusion quite like
           | forcing the heart into overdrive and massive
           | vasoconstriction. Why is the US so far behind on this???
           | 
           | This is actually quite reasonable, especially if it's paired
           | with an existing defibrillator. Epinephrine is part of the
           | advanced, cardiac life support algorithm, but it's just not
           | used in a pen format, since ACLS is typically performed in
           | the hospital setting.
           | 
           | https://cpr.heart.org/-/media/CPR-Images/CPR-Guidelines-
           | Imag...
           | 
           | Edit:
           | 
           | Recently, in the news, there was a discussion of using ECMO
           | in the setting of patients who would require CPR. Take a look
           | at this article for more:
           | https://www.nytimes.com/2024/03/27/magazine/what-to-know-
           | ecp...
        
             | refurb wrote:
             | Cardiac arrest is not the same as cardiac hypoperfusion
             | (what people commonly call a heart attack), but it can a be
             | a consequence of it.
             | 
             | Heart attacks are due to blockage of blood flow to the
             | heart. That can cause the heart to stop (cardiac arrest)
             | but not always.
        
           | nkozyra wrote:
           | Aren't epipens used sometimes to restart the heart after
           | cardiac arrest, though?
           | 
           | I don't think it's the first tool from the toolbox, but I'm
           | pretty sure epinephrine has use here.
        
             | dghughes wrote:
             | I'm not a doctor or in the medical field but I've read
             | injected lidocaine is used to treat ventricular
             | fibrillation.
             | 
             | I don't know if it's true but I am sure I also once read
             | that lidocaine can cause a heart attack but if having one
             | can help stop the heart attack.
        
               | percutaneous wrote:
               | It's not often used for what's classically considered
               | heart attacks, but it's a fun drug that can both cause
               | and fix certain arrhythmias!
        
               | epcoa wrote:
               | Ventricular Fibrillation is not a heart attack (heart
               | attack is already an imprecise lay term) but I don't
               | think encouraging it's use for anything other than acute
               | myocardial ischemia is a good idea. In that sense,
               | lidocaine doesn't stop a heart attack. A heart attack may
               | lead to arrhythmias like VF. But VF is not a heart
               | attack.
               | 
               | Lidocaine is a sodium channel blocker, it controls
               | arrhythmias by blocking or diminishing the disorganized
               | electrical activity going on in heart while hopefully not
               | squelching whatever remaining dominant organized
               | pacemaker activity there is. It is not the only
               | antiarrhythmic though and relatively not a common one
               | even for VF, it is not generally first line in its class.
               | It's role in life support is a complicated subject but it
               | is an optional drug for use in in-hospital CPR (ACLS) for
               | VT/VF. High quality CPR and defibrillation are far more
               | important though.
        
       | ImHereToVote wrote:
       | I wonder if it would be possible to inject the heart with
       | liposomal ATP directly.
        
         | robbiep wrote:
         | Even a cursory exploration into the physiology of atp would
         | demonstrate the ineffectiveness of this method - the heart
         | consumes around 6kg of ATP daily, or 250g an hour, which means
         | you'd need to provide it with more than 4g a minute just to
         | stay pumping in isolation. Which then leads to the issue of
         | actually delivering the ATP to the correct part of the heart
         | (god forbid you have a posterior infarct), and ensuring enough
         | of a quantity to keep pumping after that first bolus dose of
         | ATP, which isn't going to spread far given the lack of a
         | distribution system since there's some blockage upstream
        
       | epcoa wrote:
       | This title appears to be confusing based on a comment: Selatogrel
       | has nothing to do with epinephrine from a pharmacological
       | standpoint. It acts more like a super potent quick acting (and
       | deactivating), less blunt aspirin, an anti-platelet / anti
       | clotting drug. The comparison to epipen is just the physical
       | delivery.
       | 
       | Epinephrine is not used for heart attacks (MI) directly, but can
       | be used for cardiac arrest.
        
         | blackhaj7 wrote:
         | Definitely confusing. I read it as though I could use my epipen
         | if I had a heart attack (which feels like the opposite of what
         | you should do)
        
           | bookofjoe wrote:
           | When I posted the article on HN I put EpiPen in quotes to
           | make it less click-baity; HN's software removed the quotes,
           | thus making it both confusing and click-baity. I tried....
        
           | giantg2 wrote:
           | Epinephrine does constrict small vessels, but I think it
           | dialates the larger ones. Perhaps there would be some benefit
           | there. Although an increased heart rate would be very bad if
           | the dilation and increased BP wasn't able to put enough blood
           | past the restriction.
        
         | babypuncher wrote:
         | I didn't find it confusing. The headline had me thinking "a pen
         | that instantly delivers a life saving drug in the event of a
         | heart attack". The EpiPen is a point of comparison most people
         | are familiar with. The name of the actual drug is even right
         | there in the title (Selatogrel)
        
           | epcoa wrote:
           | > I didn't find it confusing.
           | 
           | Ok? As stated, other comments already had exposed there was
           | confusion.
           | 
           | > The name of the actual drug is even right there in the
           | title (Selatogrel)
           | 
           | Many non-experts are aware of the general practice of drug
           | companies patenting "repurposed drugs" or that the same
           | medications are marketed under different names for different
           | indications (eg Ozempic, Wegovy and Rybelsus are all the same
           | medication). I wouldn't expect most non-experts to
           | immediately know that selatogrel is a generic and not a brand
           | name, especially when it is being said in the same sentence
           | as a brand name. It is quite forgivable to assume it might be
           | an alternative trade name for an epi-pen.
        
           | starttoaster wrote:
           | It seems like it's maybe obvious what they were getting
           | across to medical layman like you and me. Seems like it's
           | less obvious to people that are a bit more in the know on
           | medical jargon.
        
             | epcoa wrote:
             | The opposite. Those, "in the know", know that selatogrel is
             | an anti-platelet medication even if they haven't heard of
             | it specifically as there is standardization to naming of
             | pharmaceuticals (the -grel in this case). The thing about
             | things that "are obvious" is that they are only that way to
             | a subset of individuals. There were evidently medical
             | laymen that were confused.
        
               | starttoaster wrote:
               | Ah, well I guess it just comes down to one's ability to
               | read between lines, I guess. More specifically, the
               | ability to read for the writer's intent rather than what
               | is plainly there. I was just trying to come up for a
               | nicer explanation to people that seem to know a lot more
               | about medicine and medical terms than me being so
               | confused by the title.
        
       | krunck wrote:
       | Ah yes: https://www.youtube.com/watch?v=jpMxpzfSRUA
        
       | westurner wrote:
       | Almost otoh, but fwiu: a Vape Pen with (which) cannabinoids may
       | be a helpful immediate intervention for ischemic Stroke?
       | 
       | Smoking increases risk of stroke and heart attack (MI: Myocardial
       | Infarction).
       | 
       | Cannabis [smoking?] is _associated with_ heart disease and MI in
       | some studies but that could be confounding e.g. preexisting
       | hypertension and other lifestyle factors.
        
         | westurner wrote:
         | (This is relevant to cardiothoraic and geriatric medicine.)
         | 
         | Why don't I just sell AEDs here. AEDs are also a heart attack
         | intervention. It looks like AEDs are about $800-$2000 USD.
         | 
         | AED: Automated External Defibrilator:
         | https://en.wikipedia.org/wiki/Automated_external_defibrillat...
        
           | TylerE wrote:
           | I suspect we will be. They were virtually unheard of a decade
           | ago (and I think the cost was closer to $10k then) but are
           | now more or less standard kit in new commercial construction.
        
           | tjohns wrote:
           | You absolutely can buy AEDs for home use, and if you're high-
           | risk it might even be a good idea.
           | 
           | The only reason it's not recommended more widely is cost
           | (they also need regular maintenance) and likelihood of
           | actually _needing_ it making it a poor medical value for the
           | general population.
           | 
           | (This is also predicated on having people around who are
           | trained to use the AED. If you life alone or your
           | family/roommates don't know how how to use it, it's useless.)
        
       | carbocation wrote:
       | The phrase "auto injector" would have been a much more helpful
       | substitute for "EpiPen" here.
       | 
       | > Selatogrel is a P2Y12 receptor antagonist
       | 
       | So this is basically like chewing on ticag, but faster.[1]
       | 
       | 1 =
       | https://jamanetwork.com/journals/jamacardiology/fullarticle/...
        
         | babypuncher wrote:
         | Most people don't know what an auto injector is. Everybody
         | knows what an EpiPen is though.
        
           | carbocation wrote:
           | I agree with you that EpiPen is far more widely known. But
           | (in my opinion) the ambiguity in the title is not worth the
           | name recognition.
        
       | caycep wrote:
       | these antiplatelets help a little bit w/ overall risk reduction
       | after a heart attack, I'd say, but the big game changer would be
       | a clot buster like an injectable version of
       | alteplase/tenecteplase or something like that. The caveat is that
       | the better it is at reversing clots, the higher risk of
       | hemorrhage; alteplase/tenecteplase is typically given in a
       | critical care/emergency Dept setting w/ surgery/intensivists
       | hovering over the patient...
        
         | et2o wrote:
         | None of these works nearly as well as angioplasty
        
           | caycep wrote:
           | yes but tpa/tnk is way closer to an angioplasty than
           | selatogrel...
        
         | anotherboffin wrote:
         | If I remember correctly, part of the goal here is to gain a bit
         | of time while the patient gets to the ER. I'm no expert but as
         | you seem to have alluded to, the risk profile of
         | alteplase/tenecteplase doesn't seem to be well suited to an
         | autoinjector with "if in doubt, use it and call the ambulance"
         | instructions.
        
           | caycep wrote:
           | yeah but then it'll have to compete w/
           | aspirin/clopidogrel...meaning they're limited on the margins
           | they can set for the med, and injectables tend to be
           | pricey...
        
       | carlsborg wrote:
       | This gentleman, Jean-Paul Clozel, exited to Johnson and Johnson
       | for $30 Billion _cash_. Ex Roche, founded Actelion
       | Pharmaceuticals with his wife in a rented lab and developed drugs
       | for rare diseases.
        
         | esel2k wrote:
         | I worked for him and also on the P2Y12 receptor antagonists.
         | What I find impressive is that it is his own money that he
         | pumps into it now as the new company is struggling to survive.
         | However the company was stretched very thin in too many disease
         | areas for the size, most of my friends lost their job in the
         | last 6 months. Glad to see some news as the share price is very
         | low currently.
        
       | pipes wrote:
       | I've recently started keeping aspirin in my pockets because I've
       | been getting unexplained horrible chest pain issues. I'm only in
       | my forties.
        
         | SketchySeaBeast wrote:
         | You, uh, don't want to get out ahead of that a bit?
        
         | Arrath wrote:
         | My friend you're going to want to get that checked out.
         | 
         | My dad thought he pulled a muscle in his chest and popped some
         | aspirin and kept truckin', in was only later when his leg
         | started swelling and turning all kinds of nasty colors that he
         | bothered to go to the hospital.
         | 
         | Turned out that a workplace injury had resulted in DVT, and he
         | had gritted his teeth through two pulmonary embolisms.
         | 
         | Still kicking to this day, largely in thanks to him finally
         | getting the issue looked at.
        
         | ww520 wrote:
         | Go to hospital to get it checked out right the way. Go to ER if
         | needed.
         | 
         | Your body is desperately trying to tell you something. Listen
         | to it.
        
           | pipes wrote:
           | I went to A&E (ER in the UK). They did two ECGs and said they
           | thought I was ok. A month a go I discovered I'm borderline
           | anemic (a consultant hematologist diagnosed this) but I've
           | been told chest pain unrelated because that only happens with
           | severe anemia. God knows what's wrong. I was sitting in my
           | car, and it feels like a fist pushing into my chest.
        
             | Madmallard wrote:
             | Sounds like angina. You're gonna want to get that more
             | thoroughly evaluated. Stress test, blood work,
             | echocardiogram, chest xray, etc...
        
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