The traditional medications that are part of GDMT for HFrEF patients were investigated in different trials including but not limited to the Perindopril in Elderly Patients with CHF (PEP-CHF) trial (angiotensin converting enzyme/ACE inhibitors), Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM)-preserved trial (angiotensin receptor blockers/ARBs), the Swedish Doppler-echocardiographic study (SWEDIC) trial (beta-blockers) and the Aldosterone Receptor Blockade in DHF (Aldo-DHF) trial (aldosterone antagonist). The gene discussed is ACE; the disease is heart failure.