Impact of sex on comparative outcomes of bivalirudin versus unfractionated heparin in patients with acute coronary syndromes undergoing invasive management: a pre-specified analysis of the MATRIX trial
Giuseppe Gargiulo 1; Bruno R. da Costa 2; Enrico Frigoli 3; Cataldo Palmieri 4; Marco Stefano Nazzaro 5; Camillo Falcone 6; Armando Liso 7; Carlo Vigna 8; Fabio Abate 9; Marco Comeglio 10; Roberto Diletti 11; Gabriele Gabrielli 12; Emilio Di Lorenzo 13; Pietro Mazzarotto 14; Marco Zimarino 15; Claudio Moretti 16; Antonio Colombo 17; Carlo Penzo 18; Giampaolo Pasquetto 19; Salvatore Brugaletta 20; Fabio Ferrari 21; Gavino Casu 22; Vincenzo Guiducci 23; Antonio Dellavalle 24; Francesco Liistro 25; Ciro Mauro 26; Arnoud W.J. van't Hof 27; Elmir Omerovic 28; Salvatore Curello 29; Jose Maria de la Torre Hernandez 30; Stefano De Servi 31; Flavia Belloni 32; Stephan Windecker 33; Marco Valgimigli 34
1. Department of Cardiology, Bern University Hospital, Bern, Switzerland and Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy; 2. Institute of Primary Health Care (BIHAM), University of Bern, Switzerland, and Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Institute of Health Policy, Management and Evaluation, University of Toronto, Canada; 3. Department of Cardiology, Bern University Hospital, Bern, Switzerland; 4. Ospedale Pasquinucci, Massa, Italy; 5. San Camillo-Forlanini, Rome, Italy; 6. Ospedale Sacra Famiglia Fatebenefratelli, Erba, Fatebenefratelli, 22036 Como CO, Italy.; 7. Citta’ di Lecce Hospital, Lecce, Italy; 8. Casa Sollievo della Sofferenza, San Giovanni Rotodondo Foggia, Viale Cappuccini, 1, 71013 San Giovanni Rotondo FG, Italy; 9. A.O. Civili Riuniti - Giovanni Paolo II - Sciacca; 10. Ospedale San Jacopo, Pistoia, Italy; 11. Thoraxcenter, Erasmus Medical, Center, Rotterdam, Netherlands; 12. Azienda Ospedali Riuniti-Presidio GM Lancisi, Ancona, Italy; 13. Ospedale San Giuseppe Moscati, Avellino AV, Italy; 14. Ospedale Maggiore, Lodi LO, Italy; 15. Università degli Studi G d’Annunzio Chieti e Pescara, Chieti, Italy; 16. A.O.U. San Giovanni Battista Molinette di Torino, Turin, Italy; 17. Department of Cardio-Thoracic and Vascular Diseases, San Raffaele Scientific Institute, Milan, Italy; 18. Ospedale Civile di Mirano, Via Zinelli, 30035, Mirano Venezia VE, Italy; 19. Ospedali Riuniti Padova Sud, Monselice PD, Italy; 20. Clinic Cardiovascular Institute, University Hospital Clinic, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain; 21. A.O. U. San Luigi Gonzaga di Orbassano Turin, Italy;; 22. Ospedale San Francesco, Nuoro, Italy; 23. Azienda USL Reggio Emilia; 24. Ospedali Riuniti ASL 17, Savigliano (CN), Italy; 25. Ospedale San Donato, Arezzo, Italy; 26. AORN Cardarelli, Napoli, Italy; 27. Maastricht University Medical Center, and Zuyderland MC, The Netherlands; 28. Sahlgrenska University Hospital, Göteborg, Sweden; 29. A.O.Spedali Civili, Brescia, Italy; 30. Hospital Marques de Valdecilla, Santander, Spain; 31. Ospedale Civile di Legnano, Legnano, Italy; 32. Ospedale Santo Spirito in Saxia, Roma, Italy; 33. From Department of Cardiology, Bern University Hospital, Bern, Switzerland; 34. Department of Cardiology, Bern University Hospital, Bern, Switzerland, Switzerland
Aims: Our aim was to assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in males and females with acute coronary syndrome (ACS) undergoing invasive management.
Methods and results: In the MATRIX programme, 7,213 patients were randomised to bivalirudin or UFH. Patients in the bivalirudin group were subsequently randomly assigned to receive or not a post-PCI bivalirudin infusion. The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding. The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target vessel revascularisation (TVR), definite stent thrombosis (ST), or NACE. The rate of MACE was not significantly lower with bivalirudin than with heparin in male (rate ratio [RR] 0.90, 95% confidence interval [CI]: 0.75-1.07; p=0.22) and female patients (RR 1.06, 95% CI: 0.80-1.40; p=0.67) without significant interaction (pint=0.31), nor was the rate of NACE (males: RR 0.85, 95% CI: 0.72-1.01; p=0.07; females: RR 0.98, 95% CI: 0.76-1.28; p=0.91; pint=0.38). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent TVR, definite ST, or NACE (males: RR 0.84, 95% CI: 0.66-1.07; p=0.15; females: RR 1.06, 95% CI: 0.74-1.53; p=0.74; pint=0.28).
Conclusions: In ACS patients, the rates of MACE and NACE were not significantly lower with bivalirudin than with UFH in both sexes. The rate of the composite of urgent TVR, definite ST, or NACE was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion in both sexes.