Rct Of Ivabradine For Ist Patients.

[jangle]

http://www.sciencedi...735109712026915

Seems like Ivabradine was successful in this trial. It is true that POTS isn't IST, but their cohort (resting pulse 88 +/- 11 bpm) and (standing pulse 108 +/- 11 bpm) and (during effort 176 +/- 17bpm)

well gosh that sounds like me. My rest pulse is 90 and my standing pulse is 120 and during exercise my rate has been known to go over 200. Even in the Mayo clinic study they're suggesting that IST and POTS might share the same mechanism.

If it works for them, it might work for some of us.

Does anyone know of people who had success with Ivabradine?

[monica]

This is very interesting! My EP Cardiologist wanted me to try Ivabradine (Bystolic) 5mg for what he thought was IST.But I never did. Another doctor who diagnosed me with P.o.t.s. wants me take Propranolol 60 mg instead. Haven't started that yet either and I have been wondering if I should try Bystolic instead since the EP said that Bystolic has fewer side effects than other beta-blockers? I too would like to know if anyone with P.o.t.s. had success with Ivabradine.

[jangle]

I think Ivabradine is different than bystolic. I'm wondering if this drug is even available in the USA?

I've looked in the past on these boards and it seems to have helped quite a few people.

[flyingsquirrel]

Ivabradine and bystolic are two VERY different drugs. Ivabradine is not available in the US or Canada. It is available in Mexico, Europe, and Australia.

Bystolic (nebivolol) is a cardioselective beta blocker that also causes nitric oxide release, and therefore vasodilation.

Procoralan (ivabradine) is a novel bradycardic agent that blocks If channels to slow the sinus node. It is NOT a beta blocker.

[rach73]

Hi

I am on ivabradine Ive been on it a little while now. I take 2.5mg three times a day (started on 2.5mg twice a day.)

Pros -

No more chest pain

not feeling like my heart is going to come out of my chest on moving ( I have quite bad pots and any change in position will do it)

I can also stand for longer without feeling like Im going to pass out.

Cons

Post prandial hypotension worse

Blood pressure low causing excessive fatigue

On occasion dropping my heart rate below 60 bpm

My sister who also has pots and eds is on this drug and has noticed a massive difference in her symptoms and no side effects.

Ive currently stopped taking it for a few days as the fatigue has been over whelming, I have to have a nap in the afternoon for three hours to be able to function in the evening.

I think its one of those drugs that works for some and not for others. My consultants concern before starting this medication was that my blood pressure would fall due to the lowered pulse. It looks like he was right. Which is a real shame and I am jealous of my sister! lol

Rach

[monica]

Oops! Sorry guys ..my bad for thinking that they were the same..brain-fog I guess

[jangle]

Hi

I am on ivabradine Ive been on it a little while now. I take 2.5mg three times a day (started on 2.5mg twice a day.)

Pros -

No more chest pain

not feeling like my heart is going to come out of my chest on moving ( I have quite bad pots and any change in position will do it)

I can also stand for longer without feeling like Im going to pass out.

Cons

Post prandial hypotension worse

Blood pressure low causing excessive fatigue

On occasion dropping my heart rate below 60 bpm

My sister who also has pots and eds is on this drug and has noticed a massive difference in her symptoms and no side effects.

Ive currently stopped taking it for a few days as the fatigue has been over whelming, I have to have a nap in the afternoon for three hours to be able to function in the evening.

I think its one of those drugs that works for some and not for others. My consultants concern before starting this medication was that my blood pressure would fall due to the lowered pulse. It looks like he was right. Which is a real shame and I am jealous of my sister! lol

Rach

Glad to hear your symptoms have been helped as well as your sister on this drug. You said it helps you not feel like you're going to pass out? My major symptom is lightheaded/presyncope, but mine is chronically felt. Does is help you with your overall lightheadedness?

There was an editorial posted about this study here:

http://content.onlin...ticleID=1358180

Which cited another study that said the longer you're on the drug the better its effects. Unfortunately it's not currently licensed in the USA, but perhaps they'll license it under the compassionate/orphan drug act.

[rach73]

Hi Jangle,

yes it stopped the pre syncope coming on - what I mean is it still came on but I got to stand up for longer (just minutes) without feeling weird.

Unfortunately the fatigue has become too much for me to handle its much more than I normally feel, this was bone crushing fatigue that was just wiping me out. So Ive stopped taking it for the time being.

Just waiting to hear from my consultant now as I rang him this morning.

Rach

[diamondcut]

I was given Ivabradine a while ago, they do offer it to POTs patiens in the UK, its used for Angina here to as it only cost £1.50 a day, so its a cheap drug. I was gutted that i had a histamine reaction to it with terrrible rash on my legs that was on fire. Such a shame as it did begin to slow my heart down and not really cause my BP to drop. I am sure it could help a lot of people in the US who cant take BB's. Wonder when it will be approved with you guys??

[jangle]

I was given Ivabradine a while ago, they do offer it to POTs patiens in the UK, its used for Angina here to as it only cost £1.50 a day, so its a cheap drug. I was gutted that i had a histamine reaction to it with terrrible rash on my legs that was on fire. Such a shame as it did begin to slow my heart down and not really cause my BP to drop. I am sure it could help a lot of people in the US who cant take BB's. Wonder when it will be approved with you guys??

It's been out for years and there really hasn't been an effort that I can tell to approve it. I don't even think the company is even going to try. The process could be decades.

[diamondcut]

And they wonder why people risk buying drugs from the internet! (Corina I am not suggesting for one moment that is what any of us should do, just simply saying i personally can see why )

Well when i say they offer it to POTs people here, its not licensed here for POTS, but we can get it. Ive read quite a lot of your old posts and your tachy rates are very much like mine, i can get breathless when nerves too, so i try my hardest not to ever get nervous becuase im lousy at hiding it lol!!! Your heart beats in your throat!

So maybe if i hadnt have reacted to it, it would have corrected the tachy, it could possibly really work for you. It must be so frustrating knowing about a drug that others in the world can get and you cant.

[jangle]

And they wonder why people risk buying drugs from the internet! (Corina I am not suggesting for one moment that is what any of us should do, just simply saying i personally can see why )

Well when i say they offer it to POTs people here, its not licensed here for POTS, but we can get it. Ive read quite a lot of your old posts and your tachy rates are very much like mine, i can get breathless when nerves too, so i try my hardest not to ever get nervous becuase im lousy at hiding it lol!!! Your heart beats in your throat!

So maybe if i hadnt have reacted to it, it would have corrected the tachy, it could possibly really work for you. It must be so frustrating knowing about a drug that others in the world can get and you cant.

Well yes it can be frustrating but it really depends on how effective it really is for POTS. I've read on this board that it has seemed to help a few people but I haven't really read cases where it was life altering like the study seems to suggest. This might be due to selection bias, obviously the people posting on this board are doing so because they haven't gotten complete relief. I do like the percentages posted by the study and I do think it is worth a try. There might be some means of obtaining the medication legally and I will ask about them at my next appointment.

[corina]

Don't worry Diamond, I understood that

Ivabradine is used in POTS here in The Netherlands too and with success as far as I know. I don't know if it's a total cure for people . I haven't tried it myself.

[jangle]

Does anyone else have any success stories with Ivabradine?

Sometimes I wonder if I have IST instead of POTS. I'm sure I've read it before, but what's the difference in diagnostic criteria between IST and POTS?

[flyingsquirrel]

I'll let someone way more qualified cover POTS, but here is what IST looks like clinically:

consistently elevated resting heart rate

inappropriate rise in heart rate in response to MINOR exertion (not necessarily postural)

hypersensitivity (inc heart rate) to beta-agonists (isoproteronol, epinephrine/adrenaline, albuterol, etc)

depressed cardiovagal tone (parasymathetic dysfunction)

rhythm must be sinus tachycardia (not SVT, etc)

I have IST (but not POTS) and my heart rate will rise from minor "exertion" like talking, eating, and walking across a room. (I also run about 8 miles a week.) None of these things are physiologically stressful for my body, it is simply an overreaction of my sympathetic nervous system AND a dysfunction of my parasympathetic system.

[jangle]

I'll let someone way more qualified cover POTS, but here is what IST looks like clinically:

consistently elevated resting heart rate

inappropriate rise in heart rate in response to MINOR exertion (not necessarily postural)

hypersensitivity (inc heart rate) to beta-agonists (isoproteronol, epinephrine/adrenaline, albuterol, etc)

depressed cardiovagal tone (parasymathetic dysfunction)

rhythm must be sinus tachycardia (not SVT, etc)

I have IST (but not POTS) and my heart rate will rise from minor "exertion" like talking, eating, and walking across a room. (I also run about 8 miles a week.) None of these things are physiologically stressful for my body, it is simply an overreaction of my sympathetic nervous system AND a dysfunction of my parasympathetic system.

That sounds like me, in fact the only parameter that was abnormal on my autonomic functioning exam was my cardiovagal system, they diagnosed me with parasympathetic dysfunction. In response to light exercise my HR shoots up quite high. Just a light jog will take me close to 200. The only thing is that my resting pulse is around 90 and not over 100, so I think that's why they diagnosed me with POTS. However, I fit the other things you mentioned.

Anymore it's looking like the research is suggesting an overlap between IST and POTS, it's probable they share many of the pathogenetic mechanisms.

All the more reason I want to try ivabradine.

[diamondcut]

I asked my last cardio can you have IST and POTs as my resting heart rate is between 90-100 usually, his answer was quite hazzy and said he felt IST was something people can live with, and its just your heart beats fast and you would have fatigue from this and not much else. IST you dont get all the nasty endless list of traits you always get with POTs.

What i dont understand and what worries me is so far i have managed to get my resting heart rate of what use to be 120 to say 90 now, and that is an improvement, but what happens if i live to forty ? and then 50? and no other meds work in the mean time, how does a resting heart rate of 90bpm effect me when i am older, that worries me. Also can anyone explain to me why abbliterations that they carry out on IST people are not done on POTs patients with high resting heart rates, i have read it makes things worse. Does anyone know more on this?

[flyingsquirrel]

Jangle...what you're describing sounds like IST to me. MANY people with a diagnosis of IST (one study said 2/3) do not have a 24 hour average HR over 100. My resting HR is around 88 and my 24 hour average HR was 85 on my last drug-free holter. It is usual for people with IST to drop down to normal HR in their sleep.

It bothers me when medical professionals dismiss IST as a 'nusiance disease'. It causes chest pain, shortness of breath, and greatly impacts quality of life. While it is true that in the majority of people it does not lead to any short term complications, in some people (myself included) a sustained high heart rate can cause a tachycardia induced cardiomyopathy which can lead to heart failure. (Usually this can be fully reversed if recognized early and treated with agressive rate control.) The long term consequences of a sustained high heart rate are not clear. Some studies have shown that a high heart rate is an independent risk factor for coronary artery disease and realted heart disease, but the true risk is not clear.

Ablations are not recommended for anyone with IST, POTS or not. There are still some people out there recommending and performing them. There are two reasons for this. One is that there is something else going on that a ablation might help with. The second is that they are subscribing to the theory that IST is a primary sinus node abnormality (rather than autonomic dysfunction). There are many studies that show that ablations are initially quite successful, but any that include long term follow-up (1 year+) show recurrence of symptoms and/or the need for a pacemaker. (There is an option for truly intractable cases that involves the complete removal of the sinus node (and sometimes the AV node) and the insertion of a permanent pacemaker.)

I would love to try ivabradine as well. IST is notoriously difficult to manage and I don't tolerate beta blockers well (they make me wheeze). Right now the comination of meds I'm on is acutally working quite well. I take a moderate does of a long acting beta blocker (nadolol) to cover the sympathetic side along with pyridostigmine to boost up the parasymathetic side. A note about pyridostigmine...I initially started taking it without a beta blocker and it actually make my heart rate go UP. There is a good physiologic explanation for this if anyone is interested, but once I combined it with a beta blocker it worked great (and all my parasymathetic autonomic testing has completley normalized).

[issie]

Yeah, flyingsquirl ---I want to know. I'm always interested in Why, What and How Come.

Issie

[flyingsquirrel]

Yeah, flyingsquirl ---I want to know. I'm always interested in Why, What and How Come.

Issie

It would be helpful to look at a picture for this, so go here...

http://emedicine.med...article/1923077

Go to the 'Gross and Microscopic Anatomy' section, then click on the image that is labled '

Sympathetic and parasympathetic neurotransmitters and receptors'.

We are only going to be talking about the top two pathways.

So...the top pathway is the parasymathetic pathway. The vagus nerve comes out of the brainstem and travels down towards lots of organs (we only care about the heart right now). It synapses (one neuron meeting another neuron) at a ganglia (a place where synapses happen) very close to the target organ (heart). The neurotransmitter that is used to transmit impulses from the pre-ganglionic neuron to the post-ganglionic neruron is acetycholine (ACh). After ACh serves its purpose in trasmitting the impulse it is quickly broken down by acetylcholinesterase (AChE) and recycled. The impulse travles down the short postganglionic neuron to the target organ (heart) where, again ACh is the neurotransmitter that transmits the impulse, this time to the heart itself.

The reason pyridostigmine is used in IST (and I think POTS ) is becasue it is an AChE inhibitor. Parasympathetic transmission is dysfunctional and, in theory, if we can increase the amout of time that ACh spends in the synapse (by delaying its breakdown), we can increase the amount of parasympathetic transmission and slow down heart rate.

This sounds great, but remember that people with IST have CRAZY strong sympathetic nervous systems and really wimpy parasympathetic nervous systems (at least when it comes to the parts that feed the heart). ACh is also the neurotransmitter between the pre-ganglionic neuron and the post-ganglionic neuron in the sympathetic pathway. The neurotransmitter between the post-ganglionic neuron and the heart is norepinephrine, which none of us lack for. Because we have an excess of norepi AND this is such a strong pathway to begin with (compared with the parasympathetic) inhibiting ACh breakdown (without any other pharmacologic intervention) has a net effect of INCREASING heart rate in people with IST. (This is not based on any research, this is based on anectodotal experience and physiology.)

In order to get a real benefit from pyridostigmine (or any AChE inhibitor), we have to attack the sympathetic side of the problem. The easiest way to do this is with a beta blocker. Even though transmission is increased a the sympathetic ganglion, it is blocked at the beta receptors on the heart.

Does this make sense?

[derekliz]

I am on Ivabradine and have been since the end of May. I LOVE it!! I am in the US and lucky to have a specialist to prescribe it. I order it online and my md faxes over a script. It is a reputable pharmacy as I asked them a zillion questions. My meds are ordered thru Canada and shipped from Germany

Liz

[derekliz]

I have a friend who is about to start it tomorrow so I am hoping that she will post here after being on in for a few daya

Liz

[jangle]

derekliz, what pharmacy do you use? If it is possible to do this, I would like to try Ivabradine myself (with prescription of course.)

Flyingsquirrel, thanks for the information. I can sympathize with the shortness of breath issue, but right now my main concern is the presyncope/lightheadedness which is my most bothersome symptom.

[issie]

Flyingsquirl,

Thanks for the explanation. I want to re-read it and sort it a little better.

I have fairly high heart rates all the time and also with movement. I thought it could also be attributed to MCAS. I know I have POTS ---could you have both?

Issie

[derekliz]

I use northwestpharmacy.com and get the generic which is 100 5mg pills for $45 and $10 shipping. I order 300 pills at a time

Liz