Thread by @drjohnm

When sacubitril/valsartan crushed it in 2014 in PARADIGM-HF for HFrEF, there were a few voices of criticism.

At #ACC21 the PARADISE-MI of entresto vs ramipril in post-MI patients w heart failure failed to show significance.

My summary
medscape.com/viewarticle/95…

Thread/

The specific message is obviously that based on this study, sac/val has no role over ACE/ARB in post-MI patients with heart failure and LV dysfunction.

We cannot ignore costs of care. And low BP was worse in the ARNI group.

The larger message--there is nearly always a larger message--is that we may have over-estimated this drug class.

It missed significance now in 2 of 3 outcome trials.
In PARAGON-HF of HFpEF and now PARADISE-MI.

Re PARADIGM, we know large effect sizes often don't replicate

Another larger message is that of #medicalconservativism and that perhaps we ought to have 2 confirmatory trials before widespread acceptance and regulatory approval.

What if PARADIGM-HF is redone with equal dose valsartan as the comparator instead of enalapril?

Let me know what you think about my arguments on @theheartorg piece

Thanks to @kaulcsmc and @VPrasadMDMPH who are both cited in the piece.