Regarding the interactions between spironolactone and ACE inhibitors or angiotensin II receptor antagonists, which were mostly incriminated in our study for causing major interactions, studies have shown that certain conditions, such as a reduced glomerular filtration rate, advanced age, T2DM, or a dose of spironolactone >25 mg daily led to severe hyperkalemia when heart failure is also associated [54]. This evidence concerns the gene ACE and heart failure.