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What predicts atrial fibrillation in ibrutinib users?

Here is an interesting clinical paper that explores predictors of atrial fibrillation in users of ibrutinib

I believe this is exactly the kind of study that we n need to see more of in this disease. In other disease areas this is the kind of thing that happens a lot. There are even large registries of patients which look at outcomes in uncontrolled real world settings. These can even be lead by the patient groups in some cases. Although the numbers or patients are not that impressive, the results are clear. Essentially, the take home message is that fibrillation is usually predictable in patients on ibrutinib in that it is much more likely to happen in people who already have abnormalities in their hearts detectable on ECG or echocardiogram (essentially an unltrasound of the heart) or have high blood pressure.

The other interesting point is that if someone develops this side effect it doesn’t necessarily mean they have to stop the drug, with one person even being fitted with a pacemaker so they could continue.

It’s a nice short paper. I would hope that others would want to replicate the results in their own patient groups. Oh how I wish we had a large registry in CLL!

ncbi.nlm.nih.gov/pmc/articl...

This is an unlocked post to allow Google to index it, so do not post anything personal in your comments that you wouldn’t want to show up in a google search.

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Having just started Ibrutinib myself this AF potential side effect has been a concern for me, something this article goes some way to allay as I am lucky enough not to have had any previous heart issues or high blood pressure. Given that most patients being treated with Ibrutinib will probably be 60+ there is an inherent risk of AF regardless of this medication (some research I have seen would indicate a 6% risk in the over 60's), the only question is by how much does this risk increase when taking Ibrutinib. I think the answer is 'not much' overall, and with no adverse heart or blood pressure issues then maybe 'hardly at all'. The reported AF incidence in the article you highlight is rather high at 16.8% compared to other larger sample studies which report the overall AF incidence on Ibrutinib to be in the range of 9-10%.

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Thanks. I think the article also makes a very interesting point that actually atrial fibrillation can be obliterated by a pacemaker if other options don’t work and let’s just say that makes it a lot easier to treat than this blasted cll we all have!

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I take ibrutinib and I just got SLAMMED with afib. I'm an otherwise healthy 60yo male, fit, lifelong runner and former triathlete who's always had hypertension. It runs in my family. We all do all the right things for it but we all have it nevertheless. I started ibrutinib six months ago in a clinical trial with obinutuzumab. It's been very successful - I tolerated it fairly well, my numbers are all in the normal range, and I've been feeling pretty good. Last week I started feeling not-so-good -- fatigued, dizzy, short of breath, agitated, and I thought I could feel my heart racing but wasn't sure (because I never knew what that actually felt like). After 3-4 days of this and a night out on the town, I stopped by the emergency room on the way home "just in case" - and they rushed me in to critical cardiac care. Heart rate was 170 and I was having serious trouble breathing. Three days later, they got it under control with Amiodarone and sent me home with a prescription for Metoprolol. The problem with getting afib is the usual blood thinners used to treat it immediately are contraindicated with ibrutinib, so they had to wait 2-3 days for the ibrutinib to clear my system. By then I was critical and they had to push a heavy dose of Amiodarone into me which put a terrible strain on my heart. The critical care team of about 12 people were standing around me with a crash cart and paddles ready for me to stroke or go into cardiac arrest. It was very alarming. If I'd been more aware of the realities of the risk with my hypertension, I may have opted for an alternative to the ibrutinib. In fact, the staff hem-onc on duty at the hospital was surprised that I was chosen for the ibrutinib trial and said he would not have recommended it. NOW they tell me!

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Creo entender que la amiodorona tambien esta contraindicado con ibrutinib. Tendras otras opciones de tratamiento, no se si Venetoclax se comporta de la misma manera que ibrutinib. Suerte!

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me referia a que amiodorona creo que tambien esta contraindicado con ibrutinib

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Gracias. I am following up with my doctors. The hard part of a crisis like this is making sure all the various doctors are in sync with each other.

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Si . Es realmente dificil

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Ventoklexa bueno

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So what are you on now? Did the Afb go away?

Rich

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I'm back up to full dose of ibrutinib (420mg) and reduced the metoprolole from 50 to 25mg and am doing fine. I wear a Fitbit to monitor my pulse 24/7. Seeing the docs over the next 2 weeks for follow-up so we'll see what the long term course of action will be.

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Tim,

Why did you not choose calquence? I had an experience exactly like yours, and did not want calquence after that. I think I will go with immunotherapy if I don't have the chromosome 17 deletion ( took the test yesterday).

Are you exercising?

Thanks,

Rich

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I didn't choose anything and don't know what calquence is. I just follow the doctor's orders and do what I'm told. I hope they know what they're doing! But I'll ask about it at my next doc appointment - thanks. And yes, I exercise - I walk 3 miles most days to/from a gym where I work out with a trainer.

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Calquence (Acalabrutinib) is a more recent daily pill which seems better than imbruvica in every, especially in not causing Afib. However, due to FDA approval, etc, insurance won't pay for it as a first line of treatment for CLL.

onclive.com/onclive-tv/dr-g...

I am glad to hear you are doing so well. Let me know how your discussion with your doctors goes.

Best,

Rich

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Hmmm. Good to know. But I'm in a clinical trial. I'm afraid I'm committed to ibrutinib for the next 3 years unless I quit or expire first. But I'll definitely ask my doc about it.

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My opinion is that you should switch to calquence if your insurance will pay for it. I would talk it over with your doctor, and ask him why you shouldn't switch. I would not stay on the imbruvica just for the sake of the clinical trial.

Let me know how things go.

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I should add that my doctor immediately recommended Calquence after my incident. However, I even fear that now, and will do immunotherapy if I can. Based on your first note, it seems you have already done that. So, you could try doing nothing for a while. The median remission time on immunotherapy alone is 26 months. My doctor said they are getting close to a cure. By the time you leave remission they might have one.

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TIm,

You mentioned you had the big attack during "a night out on the town." I assume you mean drinking a lot. I have about 2 drinks every evening, and I am suspecting my arithmia attacks are alcohol related.

You say you are doing fine now. Are you continuing to drink?

Thanks,

Rich

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No, I had not had anything to drink - not for about 10 days, in fact, since treatment and post-treatment recovery since I was feeling badly. I embellished - my "night on the town" was a movie and a teetotaling dinner with friends. When I do drink, it's very moderate - wine with dinner - a few times a week, with the approval of my doctors.

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Thanks for the information. I am beginning to think it was my nightly amitryptiline and not my 2 drinks in the evening that caused the problem.

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I have a resting pulse rate of 59

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Show off! That’s probably a sign you are really fit. But if you are worried get them to do an ECG. It’s only really on an ECG that you can tell whether or not someone has AF or other heart arrhythmias.

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I think you would feel your heart beginning to race.

My hematologist says that AF is not a reason to stop imbruvica and it’s treatable.

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Actually people aren’t always aware tho if it gets bad there’s usually other symptoms like dizziness or a low blood pressure etc. AF can sometimes be associated with a slow heart rate not a fast one.

It’s sometimes possible to sense that your pulse is irregular by feeling it in your wrist. But ultimately if you are concerned an ecg is the gold standard diagnostic tool. Sometimes people will wear a monitor for a day or longer to catch runs of altered rhythm.

See bhf.org.uk/informationsuppo...

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I strongly believe everyone going on Imbruvica (ibrutinib) clinically should have an ECG at the bear mininmum, to pick up potential heart issues...

Then an ECG, while on Imbruvica (ibrutinib) or a holter monitor, annually. Some may benefit from an echocardiogram, prior to Imbruvica (ibrutinib).

I think clinically the rate of heart issues is far higher than the often touted clinical trial figures... just my impression...

~chris

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The most disconcerting thing to me was having the staff oncologist making rounds while I was hospitalized with AFib say that with my history of hypertension, I NEVER should have been considered for ibrutinib. And at an ASH Conference banquet table full of doctors this week, they all said they're still learning about ibrutinib-related AFib and that maybe other precautions or alternatives should have been considered for me. Hindsight is always 20/20!

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I had pre-existing A.fib due to cardiotoxic drug doxirubicine in RCHOP and was on Xarelto, but this was just after Imbruvica (ibrutinib) was approved.

The combination of Imbruvica (ibrutinib) and Xarelto was unknown, just warfarin was flagged... but it certainly contibuted to my daily bleed events, huge 1/2 golfball sized blood filled blisters that appeared all over my torso.. and A.fib that was pounding in my chest.. daiky bleeds from both colon and bladder... then the Cipro was added to the mix...

After month 3, I quit it... enough was enough...

~chris

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You are indestructible!

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Hi Tim. Just read what you said. It’s interesting because this article I originally linked to would seem to suggest that if Ibrutinib is needed and strongly indicated for the disease the heart related side effects can be managed. I guess in the future hopefully the more specific future drugs will not share this problem.

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I attended a banquet at the ASH conference in San Diego last week and sat at a table full of doctors. They were all very intrigued by my experience and all acknowledged that AFib is a bigger problem with ibrutinib than originally thought. Awareness is increasing and I'm confident they're working on a fix.

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I had a major arrhythmia even last Wed, which was the day after an EKG showed no problems. I have quit Imbruvica, and would not suggest it for anyone, unless all other possibilities have been exhausted.

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my husband is doing wonderfully well on Ibrutinib for the past 9 months...

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Does your husband drink? I am beginning to think my two nightly alcoholic beverages interact badly with imbruvica.

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I like a few wines or beers (not too much any more) and didn't have any troubles on Ibrutinib. We're all different though.

It's bad enough having cancer without having to give up wine too :)

Graham

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I only have wine with food and on holidays ...

alcohol is bad for the lymphatic system

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My husband has given up alcohol and only drinks non-alcohol beer. I read several opinions and he decided to make sure that he is giving this important drug the best chance to be successful.

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You piqued my interest. Just had a checkup on Friday and looks like I have a pulse rate of 51 (BPM).

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Relaxed mode.

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As I said earlier it could be just a sign that you are really fit! But it’s probably a good idea to have an ecg done just for confidence as sometimes a low heart rate can indicate an arrhythmia. And we have enough to worry about with our health without having a niggle at the back of our minds that can be easily resolved.

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Im actually on my way to see my GP to show her my nail fungus

will enquire about a monitor

If that fails I can always call 911

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Oh don’t panic if you aren’t having symptoms. Your GP will be well placed to have a listen and decide if she thinks it sounds regular. If this is your heart rate and it’s stable and regular the chance is much more that this is a GOOD sign. Ie that your are cardiovascularly fit. And well. By all means ask them if they think you should have an ECG just to be super cautious.

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I will definitely ask! Thx Adrian!

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