Silviu Itescu The Legend, page-9

@Lymphmode Generally speaking with the SGLT2 inhibitors the placebo cohort is usually receives the best standard of care available at the time (as shown in the baseline characteristics slide below) . This information is contained in the NEJM link i provided previously for DAPAGLIFLOZIN . For example the standard of care for the placebo included diuretics 93.5%, ACEI 56.1%, Entresto (Sacubitril-Valsartan) 10.9%, ARB 26.7% etc., etc., Regarding use of Entresto, I believe part of the combination therapy also incorporates GLP-1 agonists.

If you do get time to read the full NEJM article I would draw to your attention the following comments from the accompanying editorial relating to the DAPA trial .
”This trial has some limitations. We used specific inclusion and exclusion criteria, which may have limited the generalizability of our findings. Less than 5% of the patients were black , and relatively few were very elderly with multiple coexisting illnesses. the baseline use of sacubitril vulsartan, which is more effective than renin-angiotensin system blockade alone at reducing the incidence of hospitalisation for heart failure and death from cardiovascular causes was low. However, the postulated mechanisms of action of SGLT2 inhibition and neprilysin inhibition are distinct, and in a post hoc subgroup analysis, the benefit of Dapagliflozin was similar in patients treated with sacubitril-valsartan and in those who did not receive such treatment. “


The latter observation is extremely important as it rules out a combination therapy of Entresto / DAPA and i presume other SGLT2 combinations.
As regards the Mesoblast trials . Emmerson Perrin commented that all patients in both cohorts received best standard of care at the time. I seem to recall that the sham control had 1.5% use of SGLT2 inhibitors and that use of Entresto started off at 5% when the trial first began and ended up at a level of approx 50% as it ended. From memory once again I am not sure that Entresto achieved much statistical significance in the Grade 3 patient category, whereas Mesoblast achieved statistical significance in all patients with diabetic and/or ischemia (72% of trial population of 537) regardless of being Grade 2 or 3 .


You ask a sensible question… if you look at the footnote to slide 15 on the Mesoblast link, you will see how the data can be cross referenced in industry journals. Personally I would encourage you to make yourself completely comfortable with the data. I have spent a month looking at many of the key phase 3 target inflammation studies where CRP is referenced as a biomarker for IL1Beta (Cantos Novartis) or the TNF-a studies of D L MANN somewhat earlier .Targeting ischemic heart disease primarily through one signalling pathway does not appear to me , to have the same positive clinical effect as the multimodal approach of Rexlemestrocel , which are spectacular in relation to the ischemic and/or diabetic subgroups.

I am not the only one to recognise the potential of this treatment . Many readers of Hot Copper have already read some very encouraging industry narrative…i provide one such example below. Hope this helps in your understanding of a very complex subject. OP


https://clarivate.com/blog/innovative-cardiovascular-treatments-top-pharmacotherapy-breakthroughs-at-aha21/



DYOR