Here is a recently published , large meta-analysis paper that discovered a 2 to 4 fold (200%-400%) increase in the risk of cardiovascular events for men with advanced PCa who take androgen receptor signaling inhibitor therapy (e.g., abiaterone, darolutamide, enzolamide, and apalutamide).
pubmed.ncbi.nlm.nih.gov/388...
Bob in New Mexico
An additional reason for me taking a minimal effective dose (1/10) of Bicalutamide. But, I am not advising anyone to do what I am doing 32 months now, because I am just a retired layman engineer and thus not qualified in decreasing CV events.
Followed your charting efforts to find the effective dose for the Bical.
I went from the SOC 50mg/day to every other day without any problems
Where did you end up with this? How much are you taking and over what time period?
Three, split into half, tablets or 75 mg per two weeks in 5 + 5 + 4 days succession (Tuesdays-Sundays and Wednesdays). It is about 1/10 standard dosage, but I will have to reduce it as my latest PSA came back as 0.006 which is too low for my liking. I am documenting everything in my thread entitled: "An engineer's Bicalutamide maneuvers"
I will check you B maneuvers out again.
What do you think is the dynamic here?
The long Bical half-life or does AR saturation also play a part?
My best guess is that it works based on the same (debatable) principals of BAT, a nanoBAT so to say. My endogenous tT has been from 1600 to 3300 all this time and taking half a tablet every 5 to 6 days creates a very fine sawtooth pattern like BAT does. I am planning to test this hypothesis by taking one full tablet every 10 days and see what happens. By this, the depth of the teeths will increase as well as the period of repetition. It's a long shot but worth trying.
Thanks Bob. I guess you get to chose your poison. Like we all know at our age there is no free lunch.
It's too bad that this is rarely (or never?) mentioned to patients by the oncologist.
Not that there is much of a choice depending on your cancer stage but I always prefer some informed consent.
Well, all the most reasons to eat well and to exercise a lot. Though the study does not mention the lifestyle of those participating, nor their age, nor their fitness levels pre-treatment and during treatment. Does an athlete also have a 2 to 4 fold increase in risk of CV events or is it more like younger athletic men have a 1 fold increase while older sedentary men have a 6 fold increase for an average of 2 to 4?
The average state of of health in any population of men 63-77, especially in the US, is poor when they get here. CVD has either manifested clinically or at the very least the risk is already high. Yes the risks of Lupron or similar, enzalutamide, abiraterone- all of it-should be emphasized by doctors. But what chance of that is there given that even ‘healthy’ disease free older men aren’t warned of what they’re headed for nearly enough?
I have a great many friends in our demographic without our disease or any other- who variously are substantially overweight, mostly sedentary, have terrible dietary habits ,are quite stressed and have multiple co morbidities knocking at the door. They often report that their PCP tells them that they’re ‘doing fine’ or at most get a vague suggestion to lose some weight or perhaps get a nutritionist, with little sense of urgency.
In the doctors’ defense, patients are unlikely to follow such advice anyway, mild or strong.
Even if these misleading statistics were accurate it would unlikely make much difference. We all know, at least superficially, the dangers vs benefits of these drugs, or certainly should. They delay disease progression very effectively, often for many years.
Unfortunately, for the ‘average’ man they are also gas on a robust fire. Association indeed.
My oncologist wrote the SEs down on a piece of paper while he was explaining Abi to me. One line listed High BP, edema-heart attack. I have controlled BP and no edema so I would surmise my chance of CE would be less than a guy with uncontrolled Bp and edema.
Yes, I would agree with your statement.
Yes, I would agree with your statement.
Untrue and misleading:
• Association is not causation
• All of the relative risks were 1.46-2.26 (46% greater to 126% greater)
• If the absolute risk is about 2%, 4% is a 2-fold increase, but is still a rare event.
Do these things ever show causation?
Looks to me like its a meta analysis of something you can't make head nor tails of.
This use of relative vs absolute statistics is a common statistical approach that is EXTREMELY misleading. It's not just used here, it's used everywhere. It's something you should definitely watch for.
It's hard to tell since it's quite abstract, but this just looks like a report of nonsense. I wouldn't be relying on this for anything. Or maybe you could use it as an example of something to ignore.... perhaps.
I think it's worth pointing out that, although you may indeed get CV issues due to these treatments, they may be preferable to having pain due to bone metastasis. Infact, if it was argued that this was ones strategy, to die from heart failure instead of the alternative, its a reasonable strategy.
Pain from bone metastasis can be extreme for some people and should not be underestimated. Won't be right for some, but will be right for others.
The only way to prove causation is with a randomized clinical trial.
I'll agree they provide strong evidense and are considered the gold standard.
Definitive causality? hhhhmmmm.
The study that I reported on was a random-effects meta-analysis of 22 RCT's (Randomized Controlled Trials) comprising a total of 22,166 men. Since these were randomized trials, I was correct in using the word "causation", and not "association".
"This systematic review and meta-analysis found that the addition of ARSIs to traditional ADT was associated with increased risk of CV events across the prostate cancer disease spectrum. "
I agree with you. But, if you had a pre-existing heart condition, wouldn't you want to be informed of these findings, so that you could make an informed decision?
Sure thing buddy. I'm not being critical with any intent. I just think that this isn't anything I'd be considering making any important decisions on. Others may think differently.
I do not have any preexisting condition but my oncologist send me to a cardiologist to try and prevent a heart attack when I started ADT and abiraterone. This is more important than simply informed consent. Heart disease and heart attacks are somewhat preventable. Make sure you BP is under 130 or even 120. Exercise daily. Lose weight. Take a statin and get your LDL cholesterol below 70. You should be treated like someone who has heart disease.
I like your proposals or your MO's. I dropped my Zytiga from 1k on an empty stomach to 250mg with a light breakfast. My first blood test showed my PSA as virtually unmeasurable still. My doctors ignored my proposal to have cardiac testing, and stress tests for the obvious. I am 71 in August, and near 7 years on ADT treatments. Doing well, but better and more testing is welcome.
Thank you for your kind words.
True. But, it's probably not as rare for men with pre-existing cardiovascular problems, though.
"...discovered a 2 to 4 fold (200%-400%) increase in the risk of cardiovascular events..."
Where did you see that? The abstract just says "... increased risk of CV events across the prostate cancer disease spectrum..."
I read that in a Comment that was published about the paper.
I downloaded .pdfs of the paper and the Comment. If you would like a copy, please send me an email request to: janebob99@lobo.net.
Here's the entire first paragraph of the Comment:
"In JAMA Oncology, El-Taji et al 1 report the results of a
contemporary systematic review and meta-analysis of
24 randomized clinical trials to assess the cardiovascular
(CV) impact of androgen receptor signaling inhibitors
(ARSIs) across the M0 to M1
hormone-sensitive prostate
cancer (HSPC) and castration resistant
prostate cancer (CRPC) states. The authors explored
aggregate CV events (all event types, any grade) as well as rates
of severe (grade ≥3) subcategories including hypertension,
acute coronary syndrome, arrhythmias, CV death, cerebrovascular
accident, and venous thromboembolism. The authors
observed an approximate 2-fold increased risk of any
grade (and grade ≥3) CV morbidity with the addition of
ARSI therapy, representing significantly increased risk across
all CV subcategories (except for venous thromboembolism)
and the prostate cancer (PC) disease spectrum(M0-M1 HSPC,
M0-M1 CRPC). Notably, doublet ARSI, as investigated in the
Systemic Therapy in Advancing or Metastatic Prostate Cancer:
Evaluation of Drug Efficacy (STAMPEDE) trial with
combination abiraterone acetate and enzalutamide in the
M0 to M1 states, 2 was associated with a 4-fold increased risk
of grade 3 and higher CV events."
That is what I read in the abstract's link that you first posted. I was looking for your words in the abstract, and did not see where it said "...discovered a 2 to 4 fold (200%-400%) increase in the risk of cardiovascular events..." But now I do see where you got the 2-fold and 4-fold, and I guess you provided the percentages.
Might be a reason to consider taking a break from those drugs with Intermittent ADT/"Drug holiday" if you've responded exceptionally well to these drugs after a while. I enrolled in A-Dream clinical trial (Jan of 2024) after first diagnosed in early 2022 with metastatic Prostate cancer. My body reacted well to the meds/chemo and I'm now in my 7th month of the break and my PSA is staying at 0.01 so far. Scans and PSA monitoring being done. My oncologist was all for this and did mention the long-term effects of these drugs (mine were Eligard & Zytiga with Prednisone) on your system and I was all for the break. I know it will be a "temporary" holiday but appreciate letting my "innards" rest for some months. Whatever information I could find on my own suggested there might be a slight decrease in OS (overall survival) but the difference in my opinion was still worth the break. Hoping my innards will be more ready for the next phase of the battle when mCRPC rears its ugly head.
Congratulations on your successful 7-month vacation! That's very encouraging.
Happy for your results so far. I'm not "in" the trial but following it. I'm now 2 years off all meds and still <0.01. Wishing continued success to us and all in the trial.
Your journey and holiday are impressive. From a "Badger" to a "Buckeye", let's both keep rolling along....
God Bless us all, From a Nittany Lion.
I'm favourable intermediate so no ADT needed to supplement my SBRT treatment but the oncologist was up front enough to tell me if I ever needed hormone therapy due to possible future progression that there's an increased risk of CVevents due to my previous stroke.She didn't have to tell me but good for her I say.
Hopefully won't come to that.
Maybe the CVD will knock me off my perch anyway LOL
Sounds like you have a great doctor!
I just wait till that Trolley hits me.....
Good Luck, Good Health and Good Humor.
j-o-h-n
Very interesting. It looks like there are two studies. I showed the one below to our Mayo team (cardiologist) and he said he wouldn’t comment on it. This was about 3 weeks ago. His resident seemed very curious about it. He said it would be best to see an oncology cardiologist. My husband was seeing them due to cardiovascular damage from chemotherapy and possible heart failure, which it was not. He has developed edema and tachycardia. So this is a huge concern. I posted about his crippling fatigue and the advice was to exercise, all along his heart was struggling from chemo. He’s been pulled off it. sciencedirect.com/science/a...
Background: Researchers have shown that using next-generation hormonal agents (NHA) for castration-resistantprostate cancer (CRPC) would lead to increased risk of cardiac adverse effects, making clinician choices more complex.
Methods: We systematically searched Pubmed, Cochrane Library, and Embase databases for research publishedbefore October 2022. Agents were ranked according to their effectiveness based on cardiac adverse effects usingthe surface under the cumulative ranking curve.
Results: A total of 21 Randomized Controlled Trials (RCT) with 19, 083 patients were included in present study. Our results showed that abiraterone and enzalutamide could lead to a significantly higher hypertension ratecompared with placebo; whereas no significant difference was detected between four NHAs and placebo in ischemic heart disease incidence. All four NHAs could significantly increase the risk of cardiotoxicity. Conclusions: NHAs are generally acceptable in terms of cardiovascular disease compared to placebo in patients with CRPC.ack of a head-to-head comparison of drug safety among the four NHAs
(abiraterone, enzalutamide, apalutamide, and darolutamide)
As for any kinds of cardiac disorder, the cardiotoxicity of abiraterone, enzalutamide, darolutamide and apalutamide were significantly higher than placebo (abiraterone: OR=1.63, 95% CI =1.24–2.26;
enzalutamide: OR=1.37, 95% CI =1.05–1.83; darolutamide: OR=2.39, 95% CI =1.22–4.67; apalutamide: OR=2.04, 95% CI =1.22–4.06),whereas no statistically significant difference between four types of
NHAs was detected (Table 2c). The SUCRA shows that darolutamide ranked first (SUCRA=60%), apalutamide ranked second (SUCRA=44%), abiraterone ranked third (SUCRA=59%), and enzalutamide ranked last (SUCRA=75%)
Up to now, CRPC has not been considered as curable disease, thus the current treatment goal is generally prolonging patients’ survival as longas possible without compromising the quality of life (Mohammadzadeh
et al., 2018). The treatment paradigm for CRPC has rapidly shifted over the past 5 years from ADT monotherapy to combinations of ADT with docetaxel or NHA such as abiraterone, enzalutamide, apalutamide, and darolutamide. However, data comparing these treatment options is limited. In this network meta-analysis, we comprehensively assessed the CV safety of NHA for CRPC. Overall, our results indicated that enzalutamide and abiraterone would significantly increase the risk of hypertension compared with placebo whereas ; NHA would not increase the risk of ischemic heart disease; t
In summary, the cardiac safety of NHA was systematically evaluated based on the available 21 RCTs in this Bayesian network meta-analysis. Abiraterone and enzalutamide would cause an extra risk of hypertension compared to darolutamide and apalutamide whereas there was no statistically significant difference in hypertension when compared with apalutamide, darolutamide and placebo. The NHA would not increasethe risk of ischemic heart disease but would have cardiac toxicity to varying degrees. Further studies that have longer follow-up duration, time-to-event analysis, and mortality analysis will be needed to help elucidate the full cardiac risk of NHA and help determine which to use for each demographic.
Thank you for the information.
It pays to be informed early of all of the possible bad side effects, which they are still discovering (unfortunately).
I fall on the side of trying to be informed without obsessing. He has a Family history, he takes a statin and BP pills. For now we are eating as much of the Mediterranean diet as we can. I can’t cheat him from an occasional burger or pizza. We are also walking everyday and going to add strength once he recovers a bit more from chemo. We are seeing a cardiologist once a year now. Just to be safe. I think all men with family history and advanced prostate cancer on these drugs should have baseline heart tests like an echo, EKG, stress test.
It is a difficult balance, between panicking and not worrying about it. I should be walking more every day, but it's difficult to break away from work demands...
My concern is that clinical pharmaceutical studies generally "tout" results as a decrease in relative risks not absolute risk . An even more important statistic to know would be NNT (number needed to treat) to change an outcome. This can be calculated but is almost never available.
So it is important as stated to know the difference. CV disease has a higher prevalence compared to PCa so and increase in absolute risk still would carry more weight
That's all true. I agree.
I agree with Tall_Allen that the absolute risk is not very high.
But if you're a patient with a pre-existing heart problem, then the absolute risk probably goes way up, compared to an otherwise heart-healthy patient. I'd have to study the paper to see if they separated out those patients with pre-existing heart problems. Odds are they did.
That's all true. I agree.
I agree with Tall_Allen that the absolute risk is not very high.
But if you're a patient with a pre-existing heart problem, then the absolute risk probably goes way up, compared to an otherwise heart-healthy patient. I'd have to study the paper to see if they separated out those patients with pre-existing heart problems. Odds are they did.
Huge increase in psa
Increase in hot flushes 
Continued increase in CEA & PSA Markers
2 years into Stage 4 Treatment 
Casodex causing an increase in PSA
