A sex paradox in clinical outcomes following complex percutaneous coronary intervention Johny Nicolas 1 , Bimmer E. Claessen, Davide Cao, Mauro Chiarito, Samantha Sartori, Hanbo Qiu, Ridhima Goel, Matteo Nardin, Anastasios Roumeliotis, Birgit Vogel, Ali Turfah, Rishi Chandiramani, Usman Baber, Nitin Barman, Joseph Sweeny, Prakash Krishnan, Annapoorna Kini, Samin K. Sharma, George D. Dangas, Roxana Mehran ⁎ The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA abstract article info Article history: Received 3 September 2020 Received in revised form 17 November 2020 Accepted 27 November 2020 Available online xxxx Keywords: Sex Complex PCI Female Coronary artery disease Background: Although the number of complex percutaneous coronary intervention (CPCI) procedures is increas- ing, data regarding sex-related outcomes following CPCI are scarce. Methods: We retrospectively analyzed data of patients enrolled in a single-center registry between 2009 and 2017. Patients were divided into two groups (CPCI and non-CPCI) stratified by sex. CPCI was defined as any PCI procedure with ≥1 of the following characteristics: ≥3 target vessels/lesions, ≥3 stents implanted, bifurcation with ≥2 stents, stent length > 60 mm, or chronic total occlusion. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target vessel revascularization, at oneon-year follow-up. Results: Among 20,419 patients, 5004 (24.5%) underwent CPCI of whom 25.6% (n = 1281) women and 74.4% (n = 3723) men. Women presented with more comorbidities yet less complex coronary anatomy than men (syntax score: 19.5 ± 10.3 vs. 20.6 ± 10.7, p = 0.009). Moreover, women were more likely to fulfill a single rather than multiple CPCI criteria. At one year, a higher rate of MACE occurred in women (14.0% vs. 11.6%, p = 0.02). After multivariable adjustment for confounders, the risk of MACE at one year was similar among both sexes (HR:1.04, 95% CI [0.85–1.26], p = 0.71), without significant interaction between the complexity of the procedure and sex (p-interaction = 0.96). Nonetheless, the risk of MI was significantly higher in women than men under- going CPCI (HR:1.63, 95% CI [1.12–2.38], p = 0.01). Conclusions: Despite presenting with less challenging lesions than men, women had a higher rate of MI at one year following CPCI, even after adjusting for potential confounders. © 2020 Elsevier B.V. All rights reserved. 1. Introduction Following Andreas Gruentzig's first successful coronary angioplasty in 1977, significant advances in interventional cardiology have im- proved the quality of life and survival of patients with ischemic heart disease. Although women seemed to benefit the most from the introduction of drug-eluting stents (DES), studies have generated con- flicting evidence regarding sex-related differences in outcomes follow- ing percutaneous coronary intervention (PCI) [1–4]. As a result, whether revascularization therapies should be sex-tailored is still an on- going debate [5]. A recent study pooling data from 21 randomized trials showed that, despite presenting with milder coronary artery disease (CAD) than men, women had higher rates of adverse cardiac events at 5-year follow-up [6]. These findings were recognized as the ‘Sex Para- dox’ in PCI [7]. Over the past years, PCI has been increasing in complex- ity as more patients present with advanced CAD and challenging target lesions that require cutting-edge interventional techniques [8]. The con- cept of complex PCI (CPCI) has been recently introduced, yet, no univer- sal definition exists to specify its angiographic and procedural International Journal of Cardiology xxx (2020) xxx ⁎ Corresponding author at: Center for Interventional Cardiovascular Research and Clinical Trials, Icahn School of Medicine at Mount Sinai, The Zena and Michael A. Wiener Cardiovascular Institute, One Gustave L. Levy Place, Box1030, New York, NY 10029-6574, USA. E-mail address: roxana.mehran@mountsinai.org (R. Mehran). 1 All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. IJCA-29120; No of Pages 7 https://doi.org/10.1016/j.ijcard.2020.11.067 0167-5273/© 2020 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: J. Nicolas, B.E. Claessen, D. Cao, et al., A sex paradox in clinical outcomes following complex percutaneous coronary intervention, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.11.067