[59], [60] There is evidence that these differences influence the benefits and harms of therapies. For example, the RALES RCT demonstrating the effectiveness of spironolactone in reducing hospitalization and mortality among patients with advanced HF had very low rates of adverse events. [61] The publication of the trial was followed by a marked increase in the use of spironolactone, and, among older persons who were taking ACE-inhibitors, this increase was accompanied by a substantial rise in the rates of hospitalization and mortality from hyperkalemia [62]. The gene discussed is ACE; the disease is Hyperkalemia.