Whether it is better to use a maximal dose of RASi and add an ERA (or switch to DEARA), SGLT2i, and/or MRA, depending on tolerability, or whether it is better to have the patient on low/medium doses of all drugs to gain from their different mechanisms of action, akin to the European Society of Cardiology’s 2021 Heart Failure guideline for initiation of the “Four Pillars” of treatment (69), needs to be established. This evidence concerns the gene MMP19 and heart failure.