Cardiotoxicity of Abiraterone and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer

[pjoshea13]

I don't recall this being posted:

"... the abiraterone acetate group was at greater risk of cardiovascular-related hospitalization compared to the enzalutamide group (hazard ratio (HR) 1.82 ...).

"Further, the risk of hospitalization for heart failure was greater in abiraterone acetate (HR 2.88 ...)."

urotoday.com/conference-hig...

-Patrick

[cesces]

Is the suspect mechanism the simple lowering of testosterone?

Or do they think it is more complicated or nuanced.

[pjoshea13 in reply to cesces]

Recognize that the development of Abi was a scorched earth attack on all hormones in the steroidogenesis cascade south of pregnenolone & progesterone:

en.wikipedia.org/wiki/Stero...

So, what might be the effect of removing dehydroepiandrosterone [DHEA], say, from the body? It is super-abundant normally, although there is a considerable reduction with age.

"Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men" [2014, Sweden]

"Low serum levels of DHEA and its sulfate predict an increased risk of {coronary heart disease} ..."

pubmed.ncbi.nlm.nih.gov/254...

I chose DHEA at random. One could investigate the other hormones as to their importance to cardio health.

Enza targets the AR, rather than its ligands & perhaps thats the reason

-Patrick

[Nous]

thanks for sharing this Patrick ... best wishes ... Nous

[tango65]

It seems the difference is due to a higher incidence of heart failure in the group taking abiraterone.

This is not surprising since abiraterone can cause a mineralocorticosteroid syndrome due to increase in aldosterone which leads to water retention, edema , hypertension and hypokalemia.

This situation could decompensate the heart function of people already having a reduction of the heart ejection fraction.

All the other cardiovascular complications are not significant different between abiraterone and enzalutamide.

[LearnAll in reply to tango65]

Tango..I agree what you are saying....Abiraterone has common side effect of raising Blood Pressure and high blood pressure for a long time leads to left ventricular hypertrophy eventualy culminating in congestive heart failure. Other than CHF, both drugs are eually cardiotoxic.

But if Blood pressure is well controlled with proper plant based diet, low sodium, ideal body weight and BP lowering medicines, the extra risk of heart failure can be greatly reduced.

[tango65 in reply to LearnAll]

I think the main problem may be volume overload (caused by the water and Na retention) in a patient with borderline systolic heart failure. Further dilatation of the ventricles could lead to worse systolic insufficiency or heart failure.

Hypertension and ventricular hypertrophy of the left ventricle will lead to diastolic insufficiency, but this take time, several years with significant hypertension.

[LearnAll in reply to tango65]

Exactly.....Congestive heart failure is a chronic process and takes 10 to 20 years to reach to life threatening level ...when the ejection fraction falls below 20. At terminal stage, the heart looks like "boot shaped" on X ray. Clinically it manifests as severe shortness of breath, inability to walk even 100 feet without getting short of breath.Sodium rich processed foods make it worse whereas pottassium rich fruits and vegetables slow the process of heart failure.In our cooking, we do not use regular salt because it is 100% sodium chloride. We use

"low salt" or "50/50 salt" which has 50% Sodium chloride and 50% Potassium Chloride. Keeping blood pressure equal to or less than 130/90 ertainly delays heart failure.

[kainasar]

This report may be useful.

Pharmacokinetic Interactions Between Abiraterone, Apalutamide, Darolutamide or Enzalutamide and Antithrombotic Drugs: Prediction of Clinical Events and Review of Pharmacological Information

pubmed.ncbi.nlm.nih.gov/371...