Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis

Abstract

Objectives: To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI).

Settings: A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery.

Participants: Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration <6 hours were included.

Interventions: Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor.

Outcomes: The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes.

Primary outcome: the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days.

Results: Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3-5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment.

Conclusion: In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.

Clinical trial registration: NCT01347580;Post-results.

Keywords: ATLANTIC; STEMI; gender; myocardial infarction; primary PCI; ticagrelor.

Conflict of interest statement

Competing interests: DV reports that he has no relationships relevant to the contents of this paper to disclose. SSL reports that she has no relationships relevant to the contents of this paper to disclose. JA reports receiving lecture fees from AstraZeneca. MJ reports receiving lecture fees from AstraZeneca and Sanofi. AC reports that he has no relationships relevant to the contents of this paper to disclose. MC reports that he has no relationships relevant to the contents of this paper to disclose. SGG reports receiving research grants and speaker/consulting honoraria from AstraZeneca, Daiichi-Sankyo, Eli Lilly, Sanofi, Bristol-Myers Squibb, Merck and The Medicines Company. AWvH reports receiving research and educational grants from Abbott, AstraZeneca, Eli Lilly/Daiichi-Sankyo, Merck/Correvio, Medtronic and The Medicines Company and speaker fees from Boehringer Ingelheim, Abbott, AstraZeneca, Eli Lilly/Daiichi-Sankyo, Merck/Correvio, Medtronic, The Medicines Company, Pfizer and SGM reports receiving research grants to the Institution or consulting/lecture fees from Acuitude, ADIR, Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer Ingelheim, Bristol-Myers Squibb, Brigham Women’s Hospital, Cardiovascular Research Foundation, Celladon, CME resources, Daiichi-Sankyo, Eli Lilly, Europa, Fédération Française de Cardiologie, Gilead, Hopitaux Universitaires Genève, ICAN, Janssen-Cilag, Lead-Up, Medcon International, Menarini, Medtronic, MSD, Pfizer, Recor, Sanofi-Aventis, Stentys, The Medicines Company, TIMI Study Group, Universitat Basel, WebMD and Zoll Medical. ES reports receiving lecture fees from AstraZeneca.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Cumulative Kaplan-Meier (KM) estimates of the incidence of the composite endpoint (EP) of death, MI, stroke, urgent revascularisation or definite acute stent thrombosis and all-cause mortality at 30 days by gender.

Figure 2

Association between gender and clinical efficacy and safety outcomes independent of randomised treatment.

Figure 3

Association between gender and primary and secondary outcomes, independent of randomised treatment.

Figure 4

Cumulative Kaplan-Meier (KM) estimates of the incidence of the Thrombolysis In Myocardial Infarction (TIMI) major bleeding and Bleeding Academic Research Consortium (BARC) type 3–5 bleeding at 30 days by gender.