Cardiovascular Disease in Women: Does the Effect of P2Y12 Inhibitors Differ Between Women and Men with Acute Coronary Syndrome IntroductionCardiovascular disease is a leading cause of mortality, and P2Y12 inhibitors are a cornerstone in the treatment of acute coronary syndrome (ACS). However, sex-specific differences in treatment efficacy and safety remain insufficiently explored, partly due to historically male-dominated clinical trials. The aim of this systematic literature review was to investigate whether there are sex-specific differences in the efficacy and safety of P2Y12 inhibitors in ACS treatment. MethodsA systematic literature search was conducted in PubMed, focusing on randomized controlled trials (RCT) published between 2015 and 2025. The search was structured using a block strategy incorporating free-text terms and MeSH terms related to ACS, P2Y12 inhibitors, and gender differences. Studies that included both men and women receiving P2Y12inhibitors for ACS and reported outcomes stratified by sex were selected for analysis. From an initial pool of 226 studies, six RCTs met the inclusion criteria and was selected for the literture review.ResultsThe results indicated that women generally had a higher risk of bleeding when treated with P2Y12 inhibitors, particularly with prasugrel. Some studies suggested a potential benefit of ticagrelor monotherapy in women, although this advantage diminished over time. Differences in ischemic outcomes between sexes were inconsistent, with some studies reporting a higher early risk of myocardial infarction and stroke in women, while others found no significant differences. Women also exhibited lower treatment adherence, possibly due to a higher incidence of side effects such as dyspnea. A shorter dual antiplatelet therapy (DAPT) duration appeared to reduce bleeding risk in women without increasing ischemic events. ConclusionsThe findings on sex differences in response to P2Y12 inhibitors are conflicting, with some studies suggesting that women may have a higher bleeding risk, while others do not confirm such differences. Despite this uncertainty, shorter DAPT durations may be a safer alternative for some female patients. However, the significant underrepresentation of women in clinical trials limits the reliability of these findings. Future research should focus on sex-stratified randomized trials with more balanced study populations to optimize treatment strategies for both sexes.