Sex differences in antiplatelet therapy: state-of-the art.

Antiplatelet therapy is a cornerstone of secondary prevention of cardiovascular diseases (CVDs). However, current guidelines are based on data derived primarily from men, as women are generally underrepresented in trials. Consequently, there are insufficient and inconsistent data on the effect of antiplatelet drugs in women. Sex differences were reported in platelet reactivity, patient management, and clinical outcomes after treatment with aspirin, P2Y12 inhibitor, or dual antiplatelet therapy. To evaluate whether sex-specific antiplatelet therapy is needed, in this review we discuss (i) how sex affects platelet biology and response to antiplatelet agents, (ii) how sex and gender differences translate into clinical challenges and (iii) how the cardiological care in women might be improved. Finally, we highlight the challenges faced in clinical practice regarding the different needs and characteristics of female and male patients with CVD and address issues requiring further investigation.

Antiplatelet therapy is a crucial part of cardiovascular disease prevention. Guidelines are based on data from men, as too few women participate in trials. We reviewed differences between women and men in antiplatelet therapy. Sex differences occur in platelet reactivity and in the response to the therapy with aspirin and/or P2Y₁₂ inhibitors. In primary prevention with aspirin, sex should be considered. In secondary prevention, aspirin, clopidogrel, ticagrelor, and prasugrel should be used in women as in men, according to individual patient needs. Female and male cardiac patients might present with different symptoms and risk factors. Healthcare professionals often treat women differently than men and do not satisfy women's needs. Education of researchers and healthcare professionals is required to provide highest standard of cardiological care to women. This review summarizes the evidence on sex differences in antiplatelet therapy ­ from diagnosis, through patient management, to treatment outcomes. It describes how molecular aspects translate into clinical practice and how to provide effective antiplatelet therapy to female patients.Abbreviations: ACS: acute coronary syndrome; ADP: adenosine 5'-diphosphate; BARC: Bleeding Academic Research Consortium; CAD: coronary artery disease; cAMP: cyclic adenosine 5'-monophosphate; COX-1: cyclooxygenase-1; CYP: cytochrome P; CVD(s): cardiovascular disease(s); DAPT: dual antiplatelet therapy; DES: drug-eluting stent; DM: Diabetes mellitus; GP: glycoprotein; MI: myocardial infarction; PCI: percutaneous coronary intervention; PGH₂: prostaglandin H₂; PKA: protein kinase A; TR: thromboxane receptor; TXA₂: thromboxane A₂; VASP: vasodilator-stimulated phosphoprotein; VWF: von Willebrand factor.