Type of ADT & and cardiovascular risk.

[pjoshea13]

New French study below.

Short study. Treatment began between "1st July, 2010, and the 31st December, 2011" & men were "followed ... up to 31st December, 2013."

"Among the 35,118 new ADT users, 71% received GnRH {gonadotrophin releasing hormone} agonist {such as Lupron} (reference group), 12% CAB {combined androgen blockade}, 13% AA {antiandrogen}, 3.6% GnRH antagonist {e.g. Degarelix} and 0.6% had OT {orchiectomy}."

"CAB was associated with an increased risk (adjusted HR ... 1.6 ...) and AA with a decreased risk (adjusted HR ... 0.6 ...) of ischaemic events {myocardial infarction or ischaemic stroke} when compared to GnRH agonist."

-Patrick

ncbi.nlm.nih.gov/pubmed/283...

Eur J Cancer. 2017 Apr 5;77:99-108. doi: 10.1016/j.ejca.2017.03.002. [Epub ahead of print]

Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists-a nationwide population-based cohort study based on 2010-2013 French Health Insurance data.

Scailteux LM1, Vincendeau S2, Balusson F3, Leclercq C4, Happe A3, Le Nautout B3, Polard E5, Nowak E6, Oger E7.

Author information

1

Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. Electronic address: [e-mail].

2

Urology Department, Rennes University Hospital, Rennes, France.

3

PEPS Research Consortium, Rennes Hospital University, Rennes, France.

4

Cardiology Department, Rennes University Hospital, Rennes, France.

5

Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France; PEPS Research Consortium, Rennes Hospital University, Rennes, France.

6

PEPS Research Consortium, Rennes Hospital University, Rennes, France; Université Européenne de Bretagne, Université de Brest, INSERM CIC 1412, IFR 148 et CHU de Brest, France.

7

Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France; PEPS Research Consortium, Rennes Hospital University, Rennes, France; UPRES, EA 7449, REPERES "Research in Pharmacoepidemiology and Access to Care", Rennes, France.

Abstract

BACKGROUND:

Observational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. They all compared ADT-treated cancer patients to non-treated patients or non-cancer subjects. Our aim was to evaluate whether CV risk differs by type of ADT.

METHODS:

Through nationwide population-based claims reimbursement database linked to hospital discharge database, we identified adult men with prostate cancer who initiated ADT (gonadotrophin releasing hormone [GnRH] agonist or antagonist, antiandrogen [AA], combined androgen blockade [CAB]) or had orchiectomy (OT) between 1st July, 2010, and the 31st December, 2011, and followed them up to 31st December, 2013. The main analysis followed an 'on-treatment' approach that censored all patients at the time of first therapeutic modification; it used Cox regression analysis to estimate hazard ratios (HRs) for hospitalisations for ischaemic events (myocardial infarction or ischaemic stroke, whichever came first), adjusted on age, baseline co-morbidities and taking into account death as a competing risk.

RESULTS:

Among the 35,118 new ADT users, 71% received GnRH agonist (reference group), 12% CAB, 13% AA, 3.6% GnRH antagonist and 0.6% had OT. CAB was associated with an increased risk (adjusted HR [95% confidence interval {CI}], 1.6 [1.3-2.0]) and AA with a decreased risk (adjusted HR [95% CI], 0.6 [0.4-0.9]) of ischaemic events when compared to GnRH agonist. No significant association was found with GnRH antagonist (adjusted HR [95% CI], 1.2 (0.7-2.1)).

CONCLUSION:

CV risk appeared different across ADT modalities. The probability of a clinically meaningful difference when comparing GnRH antagonists to agonists appears rather low. In a context where better overall and cancer specific survival without worsening quality of life is a challenge for clinicians, a potential heterogeneity in CV morbidity becomes crucial when choosing an ADT.

Copyright © 2017 Elsevier Ltd. All rights reserved.

KEYWORDS:

Androgen deprivation therapy; Cardiovascular morbidity; Cardiovascular risk; Ischaemic events; Prostate cancer

PMID: 28390298 DOI: 10.1016/j.ejca.2017.03.002

[BigRich]

Patrick,

The information was valuable to me.

Thank you,

Rich

[Dr_WHO]

Thank you. From some of my reading it seems like a significant number of men with prostate cancer die from heart disease than the cancer.

[pjoshea13 in reply to Dr_WHO]

Yes, & there is such a focus on the cancer, that unnecessary CVD events occur.

Dr. Myers has said that his main job with new patients is to prevent CVD death. He is dismayed that GPs haven't stepped in at a much earlier stage.

&, of course, subsequent elimination of testosterone can only make matters worse.

-Patrick

[Hidden]

CV problems was certainly a concern of mine. I am dealing with atrial fibrillation. I did have a flutter ablation to allow me to tolerate a very effective drug for atrial fibrillation: propafenone. I was given a six month eligard shot in August. I am happy to report no atrial fibrillation episodes during that time. I am quite actively pursuing a fitness program and go to the gym 3 times a week. I hit the stair climber each time I go so I consider that my 'stress test'. I think cardio fitness makes a difference. My urologist wanted me to continue on ADT for another year and a half (2 years ADT is standard for radiation). I had HIFU. No thanks on further ADT -- I want to see the results of my treatment. Will get PSA reading next month.

[Don1157]

I had a triple bypass operation within a year of starting Lupron 8 years ago. Went off Lupron after two years then. Now I am back on Lupron with concerns about further risk after the PC developed in a rib. My oncologist began talking about intermittent ADT. I am going for it!

[pjoshea13 in reply to Don1157]

Don,

CVD concern is another reason for considering testosterone [T] restoration during the off-phase of IADT.

With IADT, most men take many months for T to recover.

PSA will go up as T increases through the hypogonadal range. It will do that anyway. According to Dr. Myers, there is no extra effect once T ras reached the normal range. Which is in line with Morgenthaler, who says the androgen receptors are saturated well below the 350 ng/dL cutoff.

-Patrick

[Don1157 in reply to pjoshea13]

I will talk to him about it, Patrick, but he is kind of a conservative guy, and there was no mention of T replacement. I really appreciate your posts of original research, Patrick.