TLDR: This post is about our heart candidate. It's got 3...

TLDR: This post is about our heart candidate. It's got 3 parts:

1. The official arrival of who is IMO the most powerful figure of the revolution and how his views fit with RFK and Vinay Prasad. I’ve given a link to what I think is the best source to get to know VP. Not everyone has the time to read lengthy articles, so I’ve given a few relevant quotes.

1. I’ve tried on VP’s hat and summarised the totality of evidence from our two RCTs in HF. I welcome any corrections or additional information.

1. There’s more urgency than ever before in HF and new pressure is on the FDA, VP in particular, given what he’s spoken of publicly. I’ve put my reasoning for this pressure obliquely (but I can give further details if anyone wants) I’ve found most people don’t walk to talk about this, so you may want to skip it.

My take: VP in his own words isn’t against AA, just ramming through stuff that doesn’t work. IMO the upshot is that AA for end stage is quite possible. In light of the situation now and the new pressure, approval for the much larger indication of ischemic HF isn’t out of the question.

1. Malhotra. RFK. Prasad.

British cardiologist Dr Aseem Malhotra has been confirmed as Chief Medical Adviser of MAHA. He has a close connection to RFK Jr. AM’s main focus (leads a lobby group) is on ending the epidemic of chronic disease, focusing on the US. He’s been on a successful world tour and is now in Rome!

AM was once named one of the 50 most influential people in the world. Like Vinay Prasad, he’s long been a health campaigner. They’re broadly on the same page re. over-medication: AM has said there’s been a net harm this century; VP is laying into just about everything. This is one of the top comments on his YT talk on beta blockers:

“Can you imagine being a doctor treating Vinay for a condition and trying to prescribe him a medication?”

VP’s substack site is IMO the best way to get into his head because (supposedly) there’s less censorship:

https://www.drvinayprasad.com/

The site’s now inactive but you can still search the archive. I can’t find anything that refers to AM but since AM is going to be a close adviser to RFKjr, perhaps VP’s views on the HHS secretary might be of interest. He’s spent hours listening to him directly. In this article he says:

“The news media keeps labeling RFK Jr as a conspiracy theorist and a charlatan, but that is a colossal mistake. He is somebody who on many issues is saying something deeply true. On other issues, I think he is off the mark”.

He mentions a few things he does and doesn’t agree with. One thing he says RFK is profoundly right about is that the current system is corrupt and that pharma control FDA. Based on his articles, VP has a very low opinion of Peter Marks.

2. Heart

VP has spoken about and published and on heart therapies (at least one paper with John Ioannidis whom AM called ‘the Stephen Hawking of medicine’) Years ago he was highly critical of the Paradigm HF trial in Entresto (He goes through his analysis in articles on substack) and the LIfe trial has proven him correct.

VP is an absolute stickler for randomized trials:

“Oh, and by RCT data, I mean adequately powered RCTs measuring clinical endpoints with robust reporting and no hint of fraud”

(VP is obviously not easily impressed but I think our Dream trial meets his high standard. Cardiologist Valentin Fuster sounded impressed and congratulated the authors on their report.)

A summary of the totality of the evidence from phase 2 LVAD and Phase 3 Dream:

• Benefit in ischemic in contrast to nonischemic

• Remote effects of reduced GI bleeding (LVAD) and reduced risk of stroke (Dream HF), pointing to improving endothelial dysfunction (Merck and Bayer claim this of tablet Vericiguat.) The relationship between ischemic HF (which has a worse prognosis) and ED is well established.

• Finding that benefit is best when inflammation is present and identification of specific inflammatory biomarkers (LVAD is known to raise CRP and IL-6; Dream HF identifies elevated IL-6 and CRP.) The relationship between high inflammation (which is said to predict an increased risk of mortality), ED and ischemia is well established.

(In his YT talk on the Swedish study in beta blockers, VP looks at subgroups when he’s assessing whether or not a therapy works)

The phase 2 LVAD trial had a high percentage of nonischemic which was higher (59.4%) in the treatment group than the controls (49.1%) and yau et al say the inclusion of nonischemic could have masked efficacy. The follow-up was one year and 2 patients in the MPC group vs no controls had LVADs removed and had not undergone heart transplant. That IMO is important because explantation is said to be uncommon and if these two were ischemic then I do think this raw data is very compelling because, as the literature says, it’s even more uncommon in ischemic.

Further, If I recall right, in Dream HF the groups really started to separate out after the first year and since it’s been well over 5 years since the trial ended, I wonder if the LVAD cohort has been followed up long-term and if there were other cases of successful explantation?

Based on what Dr. Perin and SI have said, Dream HF sounds like the kind of longitudinal study that VP likes, where participants are observed over a long period of time (which was also the case for Ryoncil in aGVHD, which is in stark contrast to Rux where a consistent theme in industry literature is that long-term survival benefit is unclear)

Dream HF didn’t meet its endpoint of reducing hospitalisations. In his talk Dr. Perin mentioned briefly something about fluid on the lung. Pulmonary edema is said to be common in HF and sometimes medication (or non compliance) can worsen kidney function. Entresto was approved during the trial and if you check out online reviews, two people report fluid on the lungs, one of whom was hospitalized.

Further, 96% of participants in Dream HF were on beta blockers which can cause pulmonary edema. One of the comments on VP’s YT presentation is from a medical student who said they had a problem with this in a group of patients. Based on a comment he liked on one of his articles, VP is keen on raw data, so I’d expect he and colleagues would look at the reasons for hospitalisations for each participant: medications, dosage, compliance (including dietary) in their assessment.

3. Pressure

It looks to me like there’s intense pressure on current cardiology practices. AM comes from a landmark win in a court last year which vindicated his stance on statins. VP has laid into Entresto and you can find his talk on YT about a Swedish study he likes that questioned beta blockers as standard therapy after MI.

Check out one comment from a young man who’s had two heart attacks (and the reason for them) and has now been diagnosed with silent myocardial ischemia. He says his doctor wanted to prescribe beta blockers and asks what his options are.

There’s also pressure on AM. Australian scientist Geoff Pain says he spoke to him on his world tour and that AM knows. Given what VP (and Dr Krause) have spoken of publicly, there’s no excuse for the wilful blindness that AM is (he says) keen to end.