LindsayEdit: After I published this post, I discovered a study on the effects of ivabradine on POTS by Dr. Grubb (a well known POTS physician) and others from 2017. You can read it here, if you’re interested.
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You may remember that I participated in a clinical trial to study the effects of ivabradine (brand name: Corlanor) on postural orthostatic tachycardia syndrome (POTS) almost three years ago. I recently received an email from the study coordinators that the study had concluded and research had been published. You can read it here.
Ivabradine is a class of medication called hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers. It is typically prescribed for people with heart failure where beta blockers are not tolerated or are not managing the symptoms. Historically, beta blockers have been prescribed to lower the heart rate in people with POTS. However, beta blockers also lower blood pressure (BP). Because many people with POTS already have low BP, beta blockers are often not tolerated due to hypotension. However, ivabradine lowers heart rate without lowering blood pressure (BP) and has become more popular with POTS specialists recently. 
Hyperadrenergic POTS is characterized by high levels of norepinephrine, the neurotransmitter released as part of the “fight-or-flight” response. According to this study, in the average healthy person, norepinephrine when supine is at about 200 pg/ml and increases to 400-500 pg/ml upon standing. My supine norepinephrine measured during the test was about 500 pg/ml and 1250 pg/ml when standing.
The researchers in the study expected that, in addition to lowering heart rate, ivabradine would also lower norephinephrine levels in people with POTS. The study did show a reduction in norepinephrine levels between a placebo and ivabradine, although I presume the researchers were expecting a greater reduction. According to the data in the article, the average standing norephinephrine level on the placebo was 1,055 +/- 371.2, while the average on ivabradine was 914 +/- 358.5 – less, but perhaps not significantly so. Ivabradine also helped reduce the change in norepinephrine levels between supine and standing, a change of 442.3 /- 232.6 while on ivabradine compared to a change of 532.1 +/- 259 while on the placebo.
Ivabradine did not show a clinically significant difference in BP, although that was expected because, as noted above, ivabradine is often prescribed as an alternative to beta blockers because it does not lower BP.
The most important part of the study, however, was the conclusion that ivabradine was successful in lowering heart rate. See the chart below for the average heart rates while on ivavradine compared to the placebo:
| Ivabradine | Placebo
|
|
| Supine heart rate (bpm) | 64.9 +/- 6.5 | 77.5 +/- 12.8 |
| Standing heart rate (bpm) | 77.9 +/- 9.3 | 94.2 +/- 16.2 |
| Change in standing to sitting | 13.1 +/- 8.6 | 17.0 +/- 10.4 |
The study also asked participants about quality of life and concluded that participants reported higher quality of life while on ivabradine. I’ll let you read that part of the study yourself. I don’t have a ton of faith in quality of life questionnaires because they’re subjective, and I can admit that my response could be influenced by other factors that happened during that day.
Overall, I’m pleased with the study results. Many insurance companies won’t cover ivabradine as a treatment for POTS, and I hope this helps get better coverage for the drug. I would like to see a comparison study for beta blockers that analyzes effects on heart rate, BP, and norepinephrine levels to analyze which is better for particular symptoms when both can be tolerated. I think it’s important, however, that there were only 22 participants that completed the study. I expected a much larger number. I feel it’s difficult to make a definitive statement with such a small participant population. 
If you read my posts about my experience in the study, you know I wasn’t in love with ivabradine. Although it did slightly reduce my norepinephrine levels, it wasn’t enough to reduce my symptoms. With high supine and standing norepinephrine, I often feel like I’m in a “fight-or-flight” state. I was hoping the ivabradine would control that better, but if anything, it felt worse on ivabradine than on nothing at all. Personally, the beta blocker has always felt more effective in controlling my norepinephrine. However, because I have never had my norepinephrine tested while on a beta blocker, I cannot be sure if there’s an actual quantifiable difference.
I also tried ivabradine a few months prior to the study for a couple weeks using a free sample from my cardiologist, and wasn’t crazy about it then, either. I want to note, however, that both occurred at a rough time in my life. Halfway through the study, my mother-in-law was dying a painful death in my house from pancreatic cancer. I acknowledge that could have affected my HR and norepinephrine levels during the second half of the study – the part where I received ivabradine. I don’t want to discourage anyone from trying ivabradine, so I think it’s important to note that my experience was not typical.
I do not currently take any heart medications after making some lifestyle changes and because my resting heart rate lately is already in the 50s, or sometimes 40s when sleeping. Beta blockers, even the smallest dose possible, lower my heart rate too much. But if I felt like I needed a medication to control the tachycardia in the future, I would consider giving ivabradine one more try.
The timing of the publication of the results is important, I suppose, as the research results have been picked up by many news outlets as a possible treatment for long COVID, since, as we previously discussed, some longhaulers develop POTS. If you’re a longhauler, you might want to talk to your doctor about ivabradine. I have posted a few of the news articles below, if you’re interested. Not going to lie, I feel like a bit of a rockstar being 1 of 22 in a study that has been reported in news around the country.
“All life is an experiment.” – Ralph Waldo Emerson
Smell ya later.
– Linds
Thank you. I am a long hauler and will be asking my doctor about this med. I appreciate all of the information that you have provided.
Thanks for your comment, Danielle. I hope your doctor is able to find something that helps.
Good info! I am a hyper POTS patient but cannot take beta blockers due to asthma. I need the Bp lower component of more traditional meds though. My blood pressure is ridiculously high upon standing. I take verapamil 3-6x per day and guanfacine at night. I wish there were better options.
I’m not familiar with verapamil specifically, but am familiar with calcium channel blockers, in general, and guanfacine. Does that combination also help with the tachycardia and anxiety feelings of hyper-POTS?
Hi Linds, I felt the same with ivabradime, it just doesn’t blocks the adrenaline like beta blockers. I still take the 6mg nightly atenolol but my resting is like yours 50-60 and lower 40-50 sleeping. Except when I’ve been out and active at night…meaning socialising not running marathons (haha we wish) my heart beat feels forceful and sits more in the 70’s so I do need it then…otherwise I’m thinking of stopping it like you have. Do you get the odd forceful/higher resting beats when you’ve had a biggish day or night and do you take atenolol then or still not at all? I don’t think ivabradine would help that like a beta blocker as they block adrenaline.
Hey Jo! What a coincidence – I was just thinking about you the other day! I was thinking that i hadn’t heard from you in a while and was wondering how you were doing.
My resting HR is definitely higher on weekends, when I have possibly been out socializing, running errands, probably drinking less water, and having a little bit of alcohol. I don’t generally take atenolol even on those days, but I do always keep it in my purse just in case. If it’s a busy/crowded place, rather than just a small get together with friends (not that I do either right now during the pandemic), I might take a small dose of the atenolol. Being out and about still doesn’t raise my HR too much – probably just into the 110s at the most while standing, but more than anything I feel the adrenaline, and I still haven’t found anything that helps with that better than a beta blocker, although I am trying to find some more natural substitutes. I’m fortunate that I only need to take the beta blocker as needed. At the beginning of the pandemic my adrenaline was high and I needed it fairly regularly, but now haven’t needed it in probably 10+ months.
I hope you’re doing well, Jo! It’s great to hear from you.
Yes and no. On the days it’s really bad, the extra doses help. I have to be mindful though because it (or the POTS itself who knows) causes dizziness and a weak feeling.
The guanfacine has really helped with the anxious feeling and the really bad flushing. I feel like I need to increase my doses after a few years on it.
I’m glad to hear the guanfacine helps! Sometimes finding something that makes a difference can be the hardest part.
Well, I don’t have hyper POTS. Could it be because I take 225mg of Effexor a day? I just needed to take care of the tachycardia, which Corlanor did, and as my heart rate lowered from the usual (160-180) range, my BP came up just enough that I don’t have to force fluids and electrolytes any more. My heart rate is now in the 80-90 range during the day and I have my old life back.
POTS runs in my family. Mine was activated from having COVID last February. My granddaughter has POTS & EDS, and my niece has POTS, so my sister could also be activated.
I order mine from Canada, along with a couple of other high priced meds that are too expensive in the USA. Perfectly legal as long as the meds are for you. Until the USA changes the prescription usage from “for the use in heart failure only” to something a bit more broad, patients will still have to appeal their insurance denials, and even if they win, will still face outrageous costs. I buy mine in Canada for the cost of .54 per pill or a little more than $30.00 per month. I can live with that to have my old life back.
Thanks for your comment, Mary Beth. So glad to hear you have your old life back!
I have a few POTS friends that order ivabradine from Canadian pharmacies. I totally support that. Many drug prices are much more reasonable in Canada, and as you said, it’s perfectly legal to buy them there and have them shipped to the US. I hope these study results will help insurance companies reevaluate coverage for ivabradine and other POTS meds.
If you don’t mind me asking – if POTS runs in your family, did you ever have any kind of POTS symptoms before COVID? Did you have a severe case of COVID?
Nope. Never had any symptoms until after COVID.
I experienced what I would call a bad case of bronchitis that just wouldn’t clear up even after 2 rounds of prednisone & Z-packs separated by about a month. I had a fever for about 10 days before I went to the doctor. (I don’t go to a doctor with a fever without calling them first. I just waited this one out.) The POTS symptoms came gradually. I didn’t know why I couldn’t catch my breath & just thought it was lingering bronchitis. Random vomiting after standing for more than a few minutes and always after a bath began setting of alarm bells in my head, but only after several months. My GP called it and sent me to the cardiologist who confirmed.
Could my high dose of Effexor be the reason why I don’t experience any of the other complaints? Could it help others?
Depression also runs in my family. My birth mother committed suicide and my birth 1/2 sister had bipolar disorder. My oldest son has panic attacks and my grandson has bipolar 2 disorder. I have to take SNRI because SSRI meds always end in horrible headaches after a few years.
This is one of the most painful effects of adoption. My depression began when I was a young teenager & my mom pretty much pulled a “Snap out of it” routine with me. I finally petitioned the court to open my file in 1996 after grandchildren were being born. That was when I discovered all of my history & connected with other siblings.
You might experience even more symptoms if you weren’t taking Effexor, although that’s difficult to say for sure. Effexor is a serotonin–norepinephrine reuptake inhibitor (SNRI), which means it prevents your brain cells from absorbing two neurotransmitters, serotonin and norepinephrine. Generally, depression involves lower levels of serotonin and norepinephrine, so SNRI drugs help treat depression by increasing the levels of those neurotransmitters. Because people with hyperadrenergic POTS already have high levels of norepinephrine, SNRIs could cause some issues. However, some POTS experts do prescribe SNRIs for hyper-POTS, so it’s difficult to say for sure. Because I have hyper POTS, I, personally, would be nervous about trying an SNRI.
That being said, antidepressants (both SNRIs and SSRIs) are often prescribed off label for POTS. I’m not sure they know exactly why, but something about the antidepressant helps to regulate the autonomic nervous system. The first drug I was ever prescribed for POTS was celexa, a SSRI antidepressant. It helped a little, but I had a lot of weird side effects with it and eventually got off. Combining an antidepressant with some kind of medication that regulates the tachycardia (like a beta blocker, calcium channel blocker, or ivabradine) is a common POTS treatment.
Thanks for your reply Linds. I lost my old email account and had to find you again. I’m doing lots more these days, working more aswell, but I do struggle socially and walking around the shops. . My heart rate goes up to the 120’s/130’s at times still. I also found with the beta blockers that I get a rebound adrenaline when they are wearing off and feel awful at that time. I find with atenolol which I take at night, it’s worn off around 2-3pm and that’s when I start to feel yuck. It was worse on shorter acting BB (propranolol) happened every time it started to wear off.
Good to hear your heart rate is more under control. Will you get the Covid vaccine? My turn is coming up soon at work. We are fortunate in Australia that we have no Covid atm but it can break through again from hotel quarantine.
Sounds like you have had a lot going on, some pretty stressful things too.
i had the same rebound adrenaline with atenolol. i took it in the morning and would often wake in the middle of the night with adrenaline surges. I do plan to get the COVID vaccine. I have reservations about the possibility of long term effects, but I also have concerns about getting the virus, and the long term effects from that. It’s kind of a no-win situation.