EpiPen For Heart Attacks? Idorsia Launches Phase III Study Of Selatogrel (2021) | Hacker News Reader

EpiPen For Heart Attacks? Idorsia Launches Phase III Study Of Selatogrel (2021)

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102 pointsbookofjoe72 comments

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.

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)

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....

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.

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)

> 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.

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.

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.

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.

>I didn't find it confusing.

Great!

Anyway there are better comparisons to make if you're just trying to convey the concept of instantaneous life saving, many examples of which do not add a confounding additional pharmaceutical to draw comparisons from.

"Selatogrel: The Life Raft for Heart Attack Emergencies" was the chat-gpt recommended metaphor for avoiding pharmaceutical conflation and confusion with EpiPen.

It's basic, but then we wouldn't be discussing why Selatogrel isn't an EpiPen if the writer had considered it..

I'm in this boat, no confusion at all

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/...

Most people don't know what an auto injector is. Everybody knows what an EpiPen is though.

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.

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...

None of these works nearly as well as angioplasty

yes but tpa/tnk is way closer to an angioplasty than selatogrel...

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.

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...

You will almost certainly never see at home versions of these drugs, the risk profile is far too great. Roughly 13% of strokes are hemorrhagic and that's just the first and most obvious hazard.

Here’s the ongoing trial info: https://clinicaltrials.gov/study/NCT04957719

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.

You, uh, don't want to get out ahead of that a bit?

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.

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.

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.

Sounds like angina. You’re gonna want to get that more thoroughly evaluated. Stress test, blood work, echocardiogram, chest xray, etc…

I think you are probably right. (Or you a medic by any chance)

Edit, looking on NHS website, angina symptoms come on during exercise. This was happening while still.

Edit2: actually no, unstable angina can come on anytime

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.

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.

I wonder if it would be possible to inject the heart with liposomal ATP directly.

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

I was looking into this and haven't seen much news of late. This would be an amazing product if widely available. Unfortunately knowing the current state of US pharmaceuticals, this would cost the price of your mortgage.

pretty sure at least in Sweden they use EpiPens for a bunch of stuff, including heart attacks already?

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

> 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...

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.

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.

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.

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!

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.

Ah yes: https://www.youtube.com/watch?v=jpMxpzfSRUA

> 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.

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.

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.

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.

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.

That's far too strict. It doesn't do anyone any good to reject less effective drugs unless the safety to efficacy ratio is way off. Most drugs are relatively safe compared to the diseases they treat and identifying the subset that they work for is beyond our capability at the moment (i.e. the entirety of psychiatric medicine).

The FDA drug/therapy pipeline is supposed to give downstream users like doctors, public health officials, and patients more options within a certain risk profile. They're not supposed to be the be-all-end-all of treatment options.

Just because a drug is relatively safe doesn't mean it should be allowed if it's inferior to the existing one in all respects.

They are never inferior to existing ones in all respects for one very obvious reason: allergies.

If you’re allergic to drug A but not drug B, it doesn’t matter how much better A is than B. You need drug B.

All drugs have the potential to cause allergic reactions or other nasty side effects so unless a drug is too dangerous on its own, it should be allowed. It’s absolutely critical to deal with biochemical diversity in humans.

Good point, but many of the me-too drugs are chemically close enough to the original to cross-react. (And in some cases are actually identical--a company finds a compound the body will convert into the original drug.)

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?”

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.

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

Yes. That is how clinical trials work. I have run many clinical trials. I read the article twice before I submitted it.

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.

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.

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...

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.

It IS controlled for: ALL participants get jabbed with a needle.

Right, that's why you need to load some needles with a placebo.

Participants receiving placebo get the placebo through a needle.

Yes. I'm in favor of this.

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.

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.

(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...

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.

/? Is there a recommended placement for an AED wall cabinet within a facility? https://www.google.com/search?q=Is+there+a+recommended+place...

> How many AEDs should a facility have?

> When responding to someone who has suffered Sudden Cardiac Arrest (SCA), immediate action is critical for saving lives. The sooner that bystanders treat the SCA victim with a defibrillation shock from an Automated External Defibrillator (AED), the more likely that they will survive.

> According to [US OSHA], of the 350,000 people who die from SCA outside the hospital in the United States each year, 10,000 lives are lost in the workplace. By having defibrillators throughout offices and facilities, businesses are able to protect the lives of both their workforce and visitors.

  estimated_response_times[0] = time__to_walk_from_a_central_point * 2

ADA guidelines for AED placement: https://www.google.com/search?q=ada+guidelines+AED https://www.aedbrands.com/resources/implement/where-to-place... , AED Placement Guidelines [PDF] https://www.rescuetraininginstitute.com/wp-content/uploads/2... :

> [ height_min: 15" (38cm), max height: 48" (121cm) , max protrusion: 4" (10cm), side reach: 54" (137cm) ]

And also there are AED backpacks, which are probably easier to carry through hallways for 6 minutes (given a recommended maximum of 3 minutes each way)

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.)

I thought the whole point was that you don’t need training? Most of them literally talk you through and and all the administration is computer controlled.

You don't strictly need training to use it, but training is still strongly recommended if you want to know how to use one effectively and have the best chance of survival.

At a minimum, you need to know how to perform CPR in between shocks (or if you don't have a shockable rhythm). Ideally, you should know how to perform good CPR. The higher end ones will coach you on performing CPR, but that's definitely not universal.

Not to mention you need to figure out pad placement, possibly shave someone's chest (if they're excessively hairy), and delegate calling 911 to someone.

When seconds count you don't want to be spending minutes figuring all this out.

BLS: Basic Life Support > Method: https://en.wikipedia.org/wiki/Basic_life_support#Method :

> DRSABCD: Danger, Response, Send for help, Airway, Breathing, CPR, Defibrillation

"Drs. ABCD"

CPR: Cardiopulmonary Resuscitation: https://en.wikipedia.org/wiki/Cardiopulmonary_resuscitation

CPR > Use of Devices > Defibrillators, Devices for timing CPR, Devices for assisting in manual CPR, Devices for providing automatic CPR (*), Mobile apps for providing CPR instructions: https://en.wikipedia.org/wiki/Cardiopulmonary_resuscitation#...

/? CPR training: https://www.google.com/search?q=cpr+training &tbm=vid

/? AED CPR site:sba.gov https://www.google.com/search?q=site%3Asba.gov+AED+CPR

SBA.gov blog > Review Your Workplace Safety Policies:

> Also, consider offering training for CPR to employees. Be sure to have an automatic external defibrillator (AED) on site and have employees trained on how to use it. The American Red Cross and various other organizations offer free or low-cost training.

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