Once you stare too long into the darkness, it stares back. Thank you Vinay for not being afraid to follow the rabbit and bring it to light even 10 years ago... it will continue to take you to some very scary places.
What sickens me are the sheer number of medical "professionals" who are acting in such an evil way. It seems at times the Mexican cartels have a more lofty moral system.
In 2024, pseudo scientists paid by the industry to promote their products, would just call you names: maga, science denier and anti science, instead of engaging in a scientific debate or any critical appraisal.
Vinay, I too was troubled by Paradigm-HF when it came out, but one cardiologist after another on X kept praising Entresto to the hilt. I wondered if I was going balmy. Now I’m convinced that you and others were right and the cardiological community was sold an expensive bill of goods. Heart failure is hard to treat and manage. Expensive drugs that don’t do the job help no one.
I'm not a doctor, but I am a HFrEF patient on Entresto 97/103, now wondering if I've been throwing away all those $100+ copays I've had to pay every month for the last four years...
ite as: Zaur Gasimov. AHU 377 is commercially hidden molecula?. Authorea. January 30, 2024.
DOI: 10.22541/au.170665492.21507661/v1
Non-exclusive
No reuse
This is a preprint and has not been peer reviewed. Data may be preliminary.
AHU 377 is commercially hidden molecula?
Zaur Gasimov,MD ,Research Institute of Cardiologynamed aftervacad.J.Abdullayev,Preventive Cardiology department
ARNI-drug, which consists of two components: the blocker of angiotensin receptors -valsartan and the neprilysin inhibitor-sacubitril.(1) As a rule, the drugs available in cardiological practice, both two-component and fixed 3 or more component, consist of a combination of drugs that are successfully used as monotherapy. Examples include calcium antagonists, β-blockers, hydrochlorothiazide, indapamide, valsartan, perindopril, etc. All these drugs have been used successfully for many years as monotherapy, and nowadays, both as monotherapy and in combinations.But sacubitril is only drug in cardiovascular practice which is not recommended as monotherapy,only as combination – sacubitril/valsartan. LCZ 696 were represented by drug makers as very difficult to create, even at 696 attempt, < monolith molecule>. Cause of <not recommended> ? The reason is not entirely clear and, as I understand it, is explained by the necessity of compulsory fusion into a <single molecule> for the simultaneous release of both components of both valsartan and sacubitrile so that valsartan mitigates the negative effect of sacubitril caused NEP-dependent degradation of angiotensin II.Weak explanation,isn’t it? But No sacubitril monotherapy studies were conducted. However, a sacubitril 200 mg monotherapy arm of 165 patients was included in the HTN study CLCZ696A2201. A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Range Study to Evaluate the Efficacy and Safety of LCZ696 Comparatively to Valsartan, and to Evaluate AHU377 to Placebo After 8 Week Treatment in Patients With Essential Hypertension. In monotherapy arm, participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily. The profiles and incidence. of AEs were comparable in the sacubitril (27.3%) and placebo groups (28.3%). No deaths were reported. Therapeutic Goods Administration PO Box 100 Woden ACT 2606 Australia Email: info@tga.gov.au Phone: 1800 020 653 Fax: 02 6232 8605 https://www.tga.gov.au . Why it was not possible to use separate 2 drugs regimen of valsartan and sacubitril in pts ? I suspect,that in case of separate use of valsartan and sacubitril it will be the same clinical result as in ARNI arm. Sacubitril monotherapy is not proposed for the treatment of HF. I think that commercial purpose should not makes the door locked for sacubitril.If sacubitril(AHU 377 ) alone will be included in HF guidelines,with recommendation of use with ARB ,patients could receive AHU377 additionally to all angiotensine receptors blockers ,not only to valsartan and ,also,it will be possible to titrate doses of AHU 377 . In generally, cardiovascular drugs have adverse effects,for example, ACEi and ARB rise kalium level,but they have not “no recommended” label for this reason. (2)HCTZ treatment activate the SAS system but has no <not recommended> marker.(3)Only AHU 377 is <not recommended>.Why? Open question.
1.Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
John J.V. McMurray, M.D., Milton Packer, M.D., Akshay S. Desai, M.D., M.P.H.,
Jianjian Gong, Ph.D., Martin P. Lefkowitz, M.D., Adel R. Rizkala, Pharm.D., Jean L. Rouleau, M.D., Victor C. Shi, M.D., Scott D. Solomon, M.D., Karl Swedberg, M.D., Ph.D., and Michael R. Zile, M.D.for the PARADIGM-HF Investigators and Committees*
September 11, 2014 N Engl J Med 2014; 371:993-1004 DOI: 10.1056/NEJMoa1409077
2. Cardiovasc Therapy Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers Marsha A Raebel 1 DOI: 10.1111/j.1755-5922.2010.00258.x
Original and current comments are insightful and eloquently stated. Exceptionally accurate points and should give pause to big pharma and their sponsored docs who try to force a round peg into a square hole.........primarily for their payday. Verified truths become evident over time and should embarrass them even if it silos them.
Rindone JP, Mellen CK, Goldenstein M. Is Sacubitril/Valsartan a Superior Agent in Heart Failure With Reduced Ejection Fraction? A Review of Randomized Comparative Trials. Hosp Pharm. 2024 Jun;59(3):282-287. doi: 10.1177/00185787231212619. Epub 2023 Dec 6. PMID: 38764991; PMCID: PMC11097924.
Once you stare too long into the darkness, it stares back. Thank you Vinay for not being afraid to follow the rabbit and bring it to light even 10 years ago... it will continue to take you to some very scary places.
What sickens me are the sheer number of medical "professionals" who are acting in such an evil way. It seems at times the Mexican cartels have a more lofty moral system.
Vinay, we are lucky to have someone as capable as you standing up for your truth. Thank you.
In 2024, pseudo scientists paid by the industry to promote their products, would just call you names: maga, science denier and anti science, instead of engaging in a scientific debate or any critical appraisal.
Always good to hear your perspective on things and your willingness to be upfront about your previous views.
Vinay, I too was troubled by Paradigm-HF when it came out, but one cardiologist after another on X kept praising Entresto to the hilt. I wondered if I was going balmy. Now I’m convinced that you and others were right and the cardiological community was sold an expensive bill of goods. Heart failure is hard to treat and manage. Expensive drugs that don’t do the job help no one.
I'm not a doctor, but I am a HFrEF patient on Entresto 97/103, now wondering if I've been throwing away all those $100+ copays I've had to pay every month for the last four years...
If I were anywhere near Atlanta, I would go
Me too!
ite as: Zaur Gasimov. AHU 377 is commercially hidden molecula?. Authorea. January 30, 2024.
DOI: 10.22541/au.170665492.21507661/v1
Non-exclusive
No reuse
This is a preprint and has not been peer reviewed. Data may be preliminary.
AHU 377 is commercially hidden molecula?
Zaur Gasimov,MD ,Research Institute of Cardiologynamed aftervacad.J.Abdullayev,Preventive Cardiology department
ARNI-drug, which consists of two components: the blocker of angiotensin receptors -valsartan and the neprilysin inhibitor-sacubitril.(1) As a rule, the drugs available in cardiological practice, both two-component and fixed 3 or more component, consist of a combination of drugs that are successfully used as monotherapy. Examples include calcium antagonists, β-blockers, hydrochlorothiazide, indapamide, valsartan, perindopril, etc. All these drugs have been used successfully for many years as monotherapy, and nowadays, both as monotherapy and in combinations.But sacubitril is only drug in cardiovascular practice which is not recommended as monotherapy,only as combination – sacubitril/valsartan. LCZ 696 were represented by drug makers as very difficult to create, even at 696 attempt, < monolith molecule>. Cause of <not recommended> ? The reason is not entirely clear and, as I understand it, is explained by the necessity of compulsory fusion into a <single molecule> for the simultaneous release of both components of both valsartan and sacubitrile so that valsartan mitigates the negative effect of sacubitril caused NEP-dependent degradation of angiotensin II.Weak explanation,isn’t it? But No sacubitril monotherapy studies were conducted. However, a sacubitril 200 mg monotherapy arm of 165 patients was included in the HTN study CLCZ696A2201. A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Range Study to Evaluate the Efficacy and Safety of LCZ696 Comparatively to Valsartan, and to Evaluate AHU377 to Placebo After 8 Week Treatment in Patients With Essential Hypertension. In monotherapy arm, participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily. The profiles and incidence. of AEs were comparable in the sacubitril (27.3%) and placebo groups (28.3%). No deaths were reported. Therapeutic Goods Administration PO Box 100 Woden ACT 2606 Australia Email: info@tga.gov.au Phone: 1800 020 653 Fax: 02 6232 8605 https://www.tga.gov.au . Why it was not possible to use separate 2 drugs regimen of valsartan and sacubitril in pts ? I suspect,that in case of separate use of valsartan and sacubitril it will be the same clinical result as in ARNI arm. Sacubitril monotherapy is not proposed for the treatment of HF. I think that commercial purpose should not makes the door locked for sacubitril.If sacubitril(AHU 377 ) alone will be included in HF guidelines,with recommendation of use with ARB ,patients could receive AHU377 additionally to all angiotensine receptors blockers ,not only to valsartan and ,also,it will be possible to titrate doses of AHU 377 . In generally, cardiovascular drugs have adverse effects,for example, ACEi and ARB rise kalium level,but they have not “no recommended” label for this reason. (2)HCTZ treatment activate the SAS system but has no <not recommended> marker.(3)Only AHU 377 is <not recommended>.Why? Open question.
1.Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
John J.V. McMurray, M.D., Milton Packer, M.D., Akshay S. Desai, M.D., M.P.H.,
Jianjian Gong, Ph.D., Martin P. Lefkowitz, M.D., Adel R. Rizkala, Pharm.D., Jean L. Rouleau, M.D., Victor C. Shi, M.D., Scott D. Solomon, M.D., Karl Swedberg, M.D., Ph.D., and Michael R. Zile, M.D.for the PARADIGM-HF Investigators and Committees*
September 11, 2014 N Engl J Med 2014; 371:993-1004 DOI: 10.1056/NEJMoa1409077
2. Cardiovasc Therapy Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers Marsha A Raebel 1 DOI: 10.1111/j.1755-5922.2010.00258.x
3. Lake CR, Ziegler MG, Coleman MD, Kopin IJ. Hydrochlorothiazide-induced sympathetic hyperactivity in hypertensive patients. Clin Pharmacol Ther. 1979;26(4):428–432. [PubMed] [Google Scholar]
Clin Pharmacol Ther 1979 Oct;26(4):428-32.
doi: 10.1002/cpt1979264428.
Wow. 👏🏻👏🏻👏🏻👏🏻👏🏻
Where have all the professionals with BBBs gone?!
Original and current comments are insightful and eloquently stated. Exceptionally accurate points and should give pause to big pharma and their sponsored docs who try to force a round peg into a square hole.........primarily for their payday. Verified truths become evident over time and should embarrass them even if it silos them.
Rindone JP, Mellen CK, Goldenstein M. Is Sacubitril/Valsartan a Superior Agent in Heart Failure With Reduced Ejection Fraction? A Review of Randomized Comparative Trials. Hosp Pharm. 2024 Jun;59(3):282-287. doi: 10.1177/00185787231212619. Epub 2023 Dec 6. PMID: 38764991; PMCID: PMC11097924.