ACEi uptitration is superior to sacubitril/valsartan

PARADIGM-HF demonstrated a statistical superiority of sacubitril/valsartan versus low dose ACEi, despite US & ESC Heart Failure Guidelines recommending to uptitrate ACEi to maximum tolerated dose. This low dose comparator is the reason why, neither FDA or EMA gave a market authorisation validating superiority over ACEi.

Following PARADIGM-HF, ESC Guidelines endorsed sacubitril/valsartan as superior to ACEi, despite absence of CV Death or HF Hospitalisation reduction in Stage III/IV NYHA, (a result later confirmed by the LIFE trial), but also despite absence of benefit in MI, AF or kidney protection.

Newly published ARIADNE registry (n=9.069 HFrEF patients) just gave the real price to think sacubitril/valsartan could be superior to ACEi. Sacubitril/valsartan patients suffered a doubling rate of MI, a higher rate of stroke and no benefit on CV Death or Hospitalisation for HF.?Eventually, the rate of HF Hospitalisation was higher in sacubitril/valsartan treated patients.

ACEi remain superior to sacubitril/valsartan and must be uptitrated to its maximum tolerated dose. STRONG-HF trial, presented at the 2022 AHA, recalled it beautifuly, showing a -36% reduction of CV Death or Hospitalisation for HF when ACEI/BB/MRA are uptitrated versus actual practice of non uptitration.

Those 2 new trials strongly challenge the choice of ESC Heart Failure Guideline's to favor sacubitril/valsartan without any clear demonstration. ACEi are back, uptitrate them!