Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial
Authors: Reynolds Harmony R. , Cyr Derek D. , Merz C. Noel Bairey , Shaw Leslee J. , Chaitman Bernard R. , Boden William E. , Alexander Karen P. , Rosenberg Yves D. , Bangalore Sripal , Stone Gregg W. , Held Claes , Spertus John , Goetschalckx Kaatje , Bockeria Olga , Newman Jonathan D. , Berger Jeffrey S. , Elghamaz Ahmed , Lopes Renato D. , Min James K. , Berman Daniel S. , Picard Michael H. , Kwong Raymond Y. , Harrington Robert A. , Thomas Boban , O'Brien Sean M. , Maron David J. , Hochman Judith S. , Mavromatis Kreton , Linefsky Jason , Miller Todd , Banerjee Subhash , Reynolds Harmony R. , Newman Jonathan D. , Bangalore Sripal , Donnino Robert M. , Phillips Lawrence M. , Saric Muhamed , Abdul‐Nour Khaled , Stone Peter H. , Jang James J. , Yee Gennie , Weitz Steven , Arnold Suzanne , O’Keefe James Henry , Shapiro Michael D. , El‐Hajjar Mohammad , Sidhu Mandeep S. , Fein Steven A. , Torosoff Mikhail T. , Lyubarova Radmila , Mookherjee Sulagna , Drzymalski Krzysztof , McFalls Edward O. , Garcia Santiago A. , Bertog Stefan C. , Siddiqui Rizwan A. , Ishani Areef , Hansen Ronnell A. , Khouri Michel Georges , Goldberg Jonathan L. , Goldweit Richard , Cohen Ronny A. , Mirrer Brooks , Navarro Victor , Winchester David E. , Kronenberg Marvin , Rogal Philip , McFarren Christopher , Heitner John F. , Dauber Ira M. , Cannan Charles , Sudarshan Sriram , Mehta Puja K. , McDaniel Michael , Lerakis Stamatios , Quyyumi Arshed , Wenger Nanette K. , Hedgepeth Chester M. , Hurlburt Heather , Rosen Alan , Sahul Zakir , Booth David , Leung Steve , Abdel‐Latif Ahmed , Reda Hassan , Ziada Khaled , Setty Sampoornima , Barua Rajat S. , Hage Fadi , Caldeira Christiano , Davies James E. , Leesar Massoud , Heo Jaekyeong , Iskandrian Amy , Al Solaiman Firas , Singh Satinder , Dajani Khaled , El‐Hajjar Mohammad , Der Mesropian Paul , Sacco Joseph , McCandless Brian , Orgera Marisa , Sidhu Mandeep S. , Arif Imran , Kerr Hanan , Trejo (Gutierrez) Jorge F. , Fletcher Gerald , Lane Gary E. , Neeson Lynn M. , Parikh Pragnesh P. , Pollak Peter M. , Shapiro Brian P. , Landolfo Kevin , Gemignani Anthony , O’Rourke Daniel , Meadows Judith L. , Call Jason T. , Hannan Joseph , Bojar Robert , Kumar Deepti , Mukai John , Martin Edward T. , Vorobiof Gabriel , Moorman Alec , Kinlay Scott , Hamburger Robert J. , Rocco Thomas P. , Bhatt Deepak L. , Croce Kevin , Quin Jacquelyn A. , Anumpa Jati , Zenati Marco , Faxon David P. , Rayos Glenn , Seedhom Ashraf , Sullenberger Lance , Kumkumian Gregory , Sedlis Steven P. , Donnino Robert M. , Lorin Jeffrey , Tamis‐Holland Jacqueline E. , Kornberg Robert , Leber Robert , Saba Souheil , Lee Michael W. , Small Delano R. , Nona Wassim , Alexander Patrick B. , Rehman Iram , Badami Umesh , Marzo Kevin , Robbins Inga H. , Levite Howard A. , Shetty Sanjay , Patel Mayuri , Hamroff Glenn S. , Little Raymond W. , Zimbelman Brandi D. , Lui Charles Y. , Smith Brigham R. , Vezina Daniel P. , Khor Lillian L. , Abraham Josephine D. , Bull David A. , McKellar Stephen H. , Booth David , Kotter John , Abdel‐Latif Ahmed , Hu Bob , Labovitz Arthur J. , Berlowitz Michael , Rogal Philip , McFarren Christopher , Matar Fadi , Caldeira Christiano , Maron David J. , Rodriguez Fatima , Schnittger Ingela , Fearon William F. , Deedwania Prakash , Reddy Kiran , Sweeny Joseph , Spizzieri Christopher , Hochberg Claudia P. , Salerno William D. , Wyman Ray , Zarka Amer , Shah Anil V. , Haldis Thomas , Kohn Jeffrey A. , Girotra Saket , Almousalli Omar , Krishnam Mayil S. , Milliken Jeffrey C. , Patel Pranav M. , Seto Arnold H. , Harley Kevin T. , Gibson Michael A. , Allen Byron J. , Coram Rita , Thomas Sabu , Schwartz Ronald G. , Chen Wei , El Shahawy Mahfouz , Stafford James , Abernethy William B. , Zurick Andrew , Meyer Thomas M. , Morford Ronald G. , Rutkin Bruce , Bokhari Sabahat , Sokol Seth I. , Meisner Jay , Hamzeh Ihab , Misra Arunima , Wall Matthew , De Rosen Veronica Lenges , Alam Mahboob , Turner Michael C. , Mulhearn Thomas J. , Good Arnold P. , Shammas Nicolas W. , Chilton Robert , Nguyen Patricia K. , Jezior Matthew , Gordon Paul C. , Crain Thomas , Stenberg Robert , Pedalino Ronald P. , Wiesel Joseph , Juang George J. , Al‐Amoodi Mohammed , Wohns David , Lader Ellis W. , Mumma Michael , Dharmarajan Lekshmi , McGarvey Joseph F. X. , Downes Thomas R. , Luckasen Gary J. , Cheong Benjamin , Potluri Srinivasa , Mastouri Ronald A. , Breall Jeffery A. , Revtyak George E. , Bazeley Jonathan W. , Li Dayuan , Giedd Kenneth , Old Wayne , Burt Francis , Sokhon Kozhaya , Gopal Deepika , Valeti Uma S. , Kobashigawa Jon , Govindan Sajeev Chakanalil , Nair Rajesh Gopalan , Manjunath Cholenahally Nanjappa , Moorthy Nagaraja , Manjunath Satvic Cholenahally , Narayanappa Suryaprakash , Pandit Neeraj , Nath Ranjit Kumar , Dwivedi S. K. , Narain V. S. , Chandra Sharad , Wander Gurpreet S. , Tandon Rohit , Ralhan Sarju , Aslam Naved , Goyal Abhishek , Bhargava Balram , Karthikeyan G. , Ramakrishnan S. , Seth Sandeep , Yadav Rakesh , Singh Sandeep , Roy Ambuj , Parakh Neeraj , Verma Sunil Kumar , Narang Rajiv , Mishra Sundeep , Naik Nitish , Sharma Gautam , Choudhary Shiv Kumar , Patel Chetan , Gulati Gurpreet , Sharma Sanjeev , Bahl V. K. , Mathew Anoop , Punnoose Eapen , Gadkari Milind Avdhoot , Gadage Siddharth , Pillay Tapan Umesh , Satheesh Santhosh , Mathur Atul , Kaul Upendra , Christopher Johann , Menon Rajeev , Kumar Nirmal , Oomman Abraham , Mao Robert , Solomon Hilda , Naik Sudhir , Khan Sajeeda Parveen , Christopher Johann , Kumar Nirmal , Grant Purvez , Kachru Ranjan , Ajit Kumar V. K. , Ganapathi Sanjay , Jayakumar K. , Sivadasanpillai Harikrishnan , Sasidharan Bijulal , Kapilamoorthy T. R. , Christopher Johann , Polamuri Praneeth , Kaul Upendra , Senior Roxy , Elghamaz Ahmed , Gurunathan Sothinathan , Karogiannis Nikolaos , Shah Benoy N. , Trimlett Richard HJ , Rubens Michael B. , Nicol Edward D. , Mittal Tarun K. , Hampson Reinette , Gamma Reto Andreas , de Belder Mark A. , Thambyrajah Jeet , Nageh Thuraia , Davies John R. , Lindsay Steven J. , Kurian John , Jamil Haqeel , Raheem Osama , Hoye Angela , Donnelly Patrick , Valecka Bernardas , Chauhan Anoop , Barr Craig , Alfakih Khaled , Byrne Jonathan , Webb Ian , Henriksen Peter , OKane Peter , de Silva Ramesh , Conway Dwayne S. G. , Sirker Alexander A , Hoole Stephen P. , Witherow Fraser N. , Johnston Nicola , Harbinson Mark , Walsh Simon , Douglas Hanna , Luckie Matthew , Sobolewska Jolanta , Jeetley Paramjit , Patel Niket , Kotecha Tushar , Travill Christopher , Karimullah Iqbal , Al‐Bustami Mahmud , Braganza Denise , Henderson Robert , Pointon Kate , Naik Surendra , Mathew Thomas , Berry Colin , Collison Damien , Roditi Giles , Moriarty Andrew J. , Glover Jason D. , Pradhan Jiwan , Mikhail Ghada , Francis Darrel P. , Gosselin Gilbert , Diaz Ariel , Rheault Philippe , Barrero Miguel , Gagné Carl‐Éric , Pépin‐Dubois Yanek , Costa Ricardo , Sia Ying Tung , Lemay Catherine , Gisbert Alejandro , Gervais Pierre , Rheault Alain , Phaneuf Denis Carl , Gosselin Gilbert , Garg Pallav , Chow Benjamin J. W. , Hessian Renee C. , Beanlands Rob S. , Davies Richard F. , Bainey Kevin R. , Cheema Asim N. , Bagai Akshay , Wald Ron , Goodman Shaun , Graham John Joseph , Peterson Mark , Chow Chi‐Ming , Abramson Beth , Cheema Asim Nazir , Vakani Mohammad Tariq , Cha James , Howarth Andrew G , Wong Graham , Uxa Amar , Galiwango Paul , Kassam Saleem , Mukherjee Ashok , Ricci A. Joseph , Lam Andy , Mehta Shamir , Udell Jacob , Généreux Philippe , Hameed Adnan , Daba Ledjalem , Hueb Whady , Rezende Paulo Cury , Silva Expedito Eustáquio Ribeiro , Hueb Alexandre Ciappina , Smanio Paola Emanuela Poggio , de Quadros Alexandre Schaan , Kalil Renato Abdala Karam , da Costa Vieira José Luiz , Grossmann Gabriel , de Oliveira Pedro Píccaro , Bridi Leonardo , Savaris Simone , Vitola João V. , Cerci Rodrigo J. , Farias Fabio R. , Fernandes Miguel M. , Marin‐Neto José Antonio , Schmidt André , de Oliveira Lima Filho Moysés , Oliveira Ricardo Mendes , Chierice João Reynaldo Abbud , Polanczyk Carísi A. , Furtado Mariana V. , Smidt Luis F. , Carvalho Antonio Carlos , Pucci Gustavo , Lyra Flavio , Junior Alvaro Rabelo Alves , Dracoulakis Marianna D. A. , Lima Rodolfo G. S. D , Figueiredo Estevao , Caramori Paulo Ricardo , Tumelero Rogerio , Dall’Orto Frederico , Mesquita Claudio T. , Colafranseschi Alexandre S. , Oliveira Amarino C. , Carvalho Luiz A. , Palazzo Isabella C. , Sousa Andre S. , da Silva Expedito Eustáquio Ribeiro , de Barros Pedro Gabriel Melo , de Pádua Silva Baptista Luciana , Rodrigues Marcelo Jamus , de Resende Marcos Valério Coimbra , Saraiva Jose Francisco , Costantini Costantino , Demkow Marcin , Pracon Radoslaw , Kepka Cezary , Teresinska Anna , Kryczka Karolina , Henzel Jan , Solecki Mateusz , Kaczmarska Edyta , Mazurek Tomasz , Drozdz Jaroslaw , Czarniak Bartosz , Frach Malgorzata , Szymczyk Konrad , Niedzwiecka Iwona , Sobczak Sebastian , Ciurus Tomasz , Jakubowski Piotr , Misztal‐Teodorczyk Magdalena , Teodorczyk Dawid , Fratczak Aleksandra , Szkopiak Marcin , Lebioda Patrycja , Wlodarczyk Michal , Plachcinska Anna , Kusmierek Jacek , Miller Magdalena , Marciniak Halina , Wojtczak‐Soska Karolina , Luczak Katarzyna , Tarchalski Tomasz , Cichocka‐Radwan Anna , Szwed Hanna , Szulczyk Grazyna Anna , Witkowski Adam , Kukula Krzysztof , Celinska‐Spodar Malgorzta , Zalewska Joanna , Gajos Grzegorz , Bury Krzysztof , Pruszczyk Piotr , Roik Marek , Loboz‐Grudzien Krystyna , Sokalski Leszek , Brzezinska Barbara , Lesiak Maciej , Lanocha Magdalena , Reczuch Krzysztof W. , Kalarus Zbigniew , Swiatkowski Andrzej , Szulik Mariola , Musial Wlodzimierz J. , Bockeria Leo , Petrosyan Karen , Trifonova Tatiana , Chernyavskiy Alexander M. , Kretov Evgeniy I. , Grazhdankin Igor O. , Bershtein Leonid L. , Sayganov Sergey A. , Kuzmina‐Krutetskaya Anastasia M. , Zbyshevskaya Elizaveta V. , Katamadze Nana O. , Demchenko Elena A. , Kozlov Pavel S. , Kozulin Vikentiy Y. , Lubinskaya Ekaterina I. , Lopez‐Sendon Jose , Castro Almudena , Salicio Elena Refoyo , Guzman Gabriela , Galeote Gabriel , Valbuena Silvia , Peteiro Jesús , Martínez‐Ruíz María Dolores , Pérez‐Fernández Ruth , Cuenca‐Castillo José J. , Flores‐Ríos Xacobe , Prada‐Delgado Óscar , Barge‐Caballero Gonzalo , Juanatey Jose Ramon Gonzalez , Bayarri Miguel Souto , Nuñez Virginia Pubull , Sanchez Raymundo Ocaranza , Alvarez Belen Cid , Gil Carlos Peña , Monzonis Amparo Martinez , Sionis Alessandro , Perales Montserrat Vila , Padró Josep Maria , Peñaranda Antonio Serra , Picart Joan García , Iglesias Antonino Ginel , Marimon Xavier Garcia‐Moll , Lladó Guillem Pons , Costa Francesc Carreras , Miro Vicente , Diez Jose L. , Calvillo Pilar , Ortuño F. Marin , Chávarri M. Valdés , Montolliu A. Tello , Bermudez E. Pinar , De La Morena G. , Blancas Montserrat Gracida , Luena Jose Enrique Castillo , Fernandez‐Aviles Francisco , Chen Jiyan , Wu Yongjian , Ma Yitong , Yang Yining , Ji Zheng , Yang Xinchun , Lin Wenhua , Zeng Hesong , Fu Xin , Yang Bin , Wang Songtao , Cheng Gong , Zhao Yulan , Fang Xuehua , Zeng Qiutang , Su Xi , Li Qingxian , Nie Shao‐ping , Yu Qin , Wang Jian’an , Zhang Shuyang , Liu Zhenyu , Perna Gian Piero , Marini Marco , Gabrielli Gabriele , Provasoli Stefano , Verna Edoardo , Monti Lorenzo , Nardi Barbara , Di Chiara Antonio , Mortara Andrea , Galvani Marcello , Ottani Filippo , Sicuro Marco , Calabro Paolo , Formisano Tiziana , Tarantini Giuseppe , Cucchini Umberto , Andres Anto Luigi , Racca Emanuela , Briguori Carlo , Amati Roberto , Vergoni William , Russo Aldo , Fanelli Raffaele , Poh Kian‐Keong , Chai Ping , Lau Titus , Loh Joshua P. , Tay Edgar L. , Teoh Kristine , Teo Lynette L. , Ong Ching‐Ching , Wong Raymond C. , Loh Poay‐Huan , Kofidis Theodoros , Chan Wan Xian , Chan Koo Hui , Foo David , Kong Jason Loh Kwok , Er Ching Min , Jafary Fahim Haider , Chua Terrance , Doerr Rolf , Stumpf Juergen , Matschke Klaus , Simonis Gregor , Kadalie Clemens T. , Sechtem Udo , Ong Peter , Schulze P. Christian , Goebel Bjoern , Lenk Karsten , Nickenig Georg , Schuchlenz Herwig , Weikl Stefan , Lang Irene Marthe , Huber Kurt , Jakl‐Kotauschek Gabriele , Vertes Andras , Varga Albert , Fontos Geza , Merkely Bela , Kerecsen Gabor , Hinic Sasa , Zdravkovic Marija , Mudrenovic Vladan , Crnokrak Bogdan , Beleslin Branko D. , Boskovic Nikola N. , Petrovic Marija T. , Dobric Milan R. , Markovic Zeljko Z. , Mladenovic Ana S. , Cemerlic‐Adjic Nada , Davidovic Goran , Vucic Rada , Dekleva Milica Nikola , Stankovic Goran , Apostolovic Svetlana , Escobedo Jorge , Baleón‐Espinosa Rubén , Campos‐Santaolalla Arturo S. , Durán‐Cortés Elihú , Flores‐Palacios José M. , García‐Rincón Andrés , Jiménez‐Santos Moisés , Peñafiel Joaquín V. , Ortega‐Ramírez José A. , Valdespino‐Estrada Aquiles , Rosas Erick Alexánderson , Selvanayagam Joseph B. , Joseph Majo X. , Thambar Suku T. , Beltrame John F. , Hillis Graham S. , Thuaire Christophe , Dutoiu Téodora , Steg Philippe Gabriel , Juliard Jean‐Michel , Slama Michel S. , El Mahmoud Rami , Nicollet Eric , Goube Pascal , Barone‐Rochette Gilles , Furber Alain , Bière Loïc , Laucevicius Aleksandras , Celutkiene Jelena , Kedhi Elvin , Timmer Jorik , Hermanides Rik , Kaplan Eliza , Riezebos Robert K. , Samadi Pouneh , van Dongen Elise , Niehe Sander R. , Suryapranata Harry , van Vugt Stijn , Ramos Ruben , Cacela Duarte , Santana Ana , Fiarresga Antonio , Sousa Lidia , Marques Hugo , Patricio Lino , Bernanrdes Luis , Rio Pedro , Carvalho Ramiro , Ferreira Rui , Silva Tiago , Rodrigues Ines , Modas Pedro , Portugal Guilherme , Fragata Jose , Pinto Fausto J. , Menezes Miguel Nobre , Lopes Guilhermina Cantinho , Almeida Ana Gomes , Silva Pedro Canas , Nobre Angelo , Francisco Ana Rita , Ferreira Nuno , Lopes Ricardo L. , Guzman Luis , Figal Julio César , Méndiz Oscar , Cortés Claudia , Favaloro Roberto René , Alvarez Carlos , Courtis Javier , Zeballos Gabriela , Schiavi Lilia , Rubio Mariano , Devlin Gerard Patrick , Fisher Raewyn , Stewart Ralph Alan Huston , White Harvey Douglas , Benatar Jocelyne , Kedev Sasko , Mitevska Irena Peovska , Kostovska Elizabeta Srbinovska , Pejkov Hristo , Held Claes , Eggers Kai , Frostfelt Gunnar , Johnston Nina , Olsowka Maciej , Åkerblom Axel , Soveri Inga , Aspberg Johannes , Sharir Tali , Elian Dan , Kerner Arthur , Massalha Samia , Fukuda Keiichi , Kohsaka Shun , Yasuda Satoshi , Nishimura Shigeyuki , Goetschalckx Kaatje , Van de Werf Frans , Claes Kathleen , Hung Chung‐Lieh , Yun Chun‐Ho , Hou Charles Jia‐Yin , Kuo Jen‐Yuan , Yeh Hung‐I , Hung Ta‐Chuan , Li Jiun‐Yi , Chien Chen‐Yen , Tsai Cheng‐Ting , Liu Chun‐Chieh , Yu Fa‐Chang , Lin Yueh‐Hung , Lan Wei‐Ren , Yen Chih‐Hsuan , Tsai Jui‐Peng , Sung Kuo‐Tzu , Ntsekhe Mpiko , Pandie Shaheen , Viljoen Charle A. , De Andrade Marianne , Moccetti Tiziano , Rossi M. Grazia , Abdelhamid Magdy , Adel Ahmed , Kamal Ahmed , Mahrous Hossam , El Kaffas Sameh , El Fishawy Hussien , Pop Calin , Claudia Matei , Popescu Bogdan A. , Ginghina Carmen , Deleanu Dan , Iliescu Vlad A. , Al‐Mallah Mouaz H. , Aljzeeri Ahmed , Najm Hani , Alghamdi Ali , Ramos Walter Enrique Mogrovejo , Kuanprasert Srun , Prommintikul Arintaya , Nawarawong Weerachai , Woragidpoonpol Surin , Tepsuwan Thitipong , Taksaudom Noppon , Rimsukcharoenchai Chataroon , Euathrongchit Juntima , Wannasopha Yutthaphan , Yamwong Sukit , Sritara Piyamitr , Aramcharoen Suthara , Meemuk Krissada , Khairuddin Ahmad , Hadi Hafidz Abd , Yahaya Shaiful Azmi 
Published: February 2024

Background
Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.

Methods and Results

The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men;
P
<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (
P
<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (
P
=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13];
P
=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14];
P
=0.49), with no significant sex‐by‐treatment‐group interactions.

Conclusions
Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial.

Registration

URL:
http://wwwclinicaltrials.gov
. Unique identifier: NCT01471522.