Sex, drugs, and heart failure: a sex-sensitive review of the evidence base behind current heart failure clinical guidelines

Heart failure (HF) is a complex disease, almost as common in women as in men. Nonetheless, HF clinical presentation, prognosis, and aetiology vary by sex. This review summarizes the current state of sex-sensitive issues related to HF drugs included in treatment guidelines and suggests future directions for improved care. Heart failure presentation differs between female and male patients: females more often show with hypertensive aetiology and the preserved ejection fraction phenotype, while men more often show ischaemic aetiology and the reduced ejection fraction phenotype. Yet the HF clinical guidelines in Europe, the United States, and Canada do not reflect the sexual dimorphism. Further, in randomized clinical trials of HF medication, women are largely underrepresented, typically consisting of 70% men. Given the knowledge that some adverse drug reactions, such as torsade de pointes and angiotensin-converting enzyme inhibitor-induced cough, occur more frequently in women, we emphasize the need to test medications thoroughly in both sexes and explore sexual dimorphisms. To better represent all of the targeted patient population and provide better care for all, two kinds of change must come about: recruitment methods to randomized clinical trial samples need to evolve and the participation needs to seem more attractive to women.