Sex-related differences in cardiovascular pharmacotherapy: fiction or fact? . Why can't we see the evidence?

There are sex-related differences (SRD) in body composition and physiology, and in the pharmacokinetics, efficacy, safety and dosing of some cardiovascular drugs. Thus, men and women may respond differently to certain drugs. However, information on SRD in efficacy, safety and dosage of cardiovascular drugs is scarce and their clinical relevance remains uncertain mainly due to the traditional under-representation of women and drug efficacy and safety is not reported in a sex-disaggregated manner in randomized clinical trials (RCT). Thus, many RCT were unpowered to analyze and detect SRD, even if they do exist, and clinical practice guidelines (CPG) based on these RCT recommend (with few exceptions) to treat women like men. Furthermore, women are less likely to receive CPG-recommended cardiovascular drugs (CPGRD), present more adverse drug reactions and may require lower doses of some drugs than men. In the era of “precision medicine”, this limited information should stimulate basic and clinical research to better understand the mechanisms underlying these SRD in the efficacy and safety of CPGRD because this represents the first step to develop a personalized pharmacotherapy. The aim of this narrative review is to analyse the reasons and consequences of the limited information on SRD in efficacy, safety and dosing of CPGRD, whether the recommended doses are appropriate for women, the differences in the use of CPGRD, and finally, formulate recommendations to close our gaps in knowledge about SRD and reverse the current situation to improve CVD prevention and treatment from a sex-specific perspective.