In Reply The letter by McCarthy and McEvoy illustrates the distinctive process that permeates the thinking of physicians who treat heart failure in contrast to those who treat cancer. Oncologists enthusiastically use drugs in high doses in the hope that they might prolong life, knowing with certainty that the drugs cause serious adverse effects. In contrast, cardiologists hesitate to use a drug that has been demonstrated (beyond a reasonable doubt) to prolong life simply because someone raises the hypothetical concern about an unobserved adverse effect that might occur 10 to 20 years later. McCarthy and McEvoy make reference to the concerns of the US Food and Drug Administration about the risk of dementia with sacubitril/valsartan; fortunately, their position is far more reassuring than the authors of the letter have conveyed. A comprehensive summary of the regulatory position on the safety of the drug has recently been published.¹