Survival After Invasive or Conservative Management of Stable Coronary Disease
Authors: Hochman Judith S. , Anthopolos Rebecca , Reynolds Harmony R. , Bangalore Sripal , Xu Yifan , O’Brien Sean M. , Mavromichalis Stavroula , Chang Michelle , Contreras Aira , Rosenberg Yves , Kirby Ruth , Bhargava Balram , Senior Roxy , Banfield Ann , Goodman Shaun G. , Lopes Renato D. , Pracoń Radosław , López-Sendón José , Maggioni Aldo Pietro , Newman Jonathan D. , Berger Jeffrey S. , Sidhu Mandeep S. , White Harvey D. , Troxel Andrea B. , Harrington Robert A. , Boden William E. , Stone Gregg W. , Mark Daniel B. , Spertus John A. , Maron David J. , Hochman Judith S. , Maron David J. , Reynolds Harmony R. , Bangalore Sripal , Mavromichalis Stavroula , Chang Michelle , Contreras Aira , Esquenazi-Karonika Shari , Gilsenan Margaret , Gwiszcz Ewelina , Mathews Patenne , Mohamed Samaa , Naumova Anna , Roberts Arline , VanLoo Kerrie , Anthopolos Rebecca , Xu Yifan , Troxel Andrea B. , Lu Ying , Huang Zhen , Broderick Samuel , Guzmán Luis , Selvanayagam Joseph , Lopes Renato D. , Goodman Shaun G. , Steg Gabriel , Juliard Jean-Michel , Doerr Rolf , Keltai Matyas , Bhargava Balram , Thomas Boban , Sharir Tali , Nikolsky Eugenia , Maggioni Aldo P. , Kohsaka Shun , Escobedo Jorge , White Harvey D. , Pracoń Radosław , Bockeria Olga , López-Sendón José , Held Claes , Senior Roxy , Banfield Ann , Shaw Leslee J. , Phillips Lawrence , Berman Daniel , Kwong Raymond Y. , Picard Michael H. , Chaitman Bernard R. , Ali Ziad , Min James , Mancini G.B. John , Leipsic Jonathon , Guzmán Luis , Hillis Graham , Thambar Suku , Joseph Majo , Selvanayagam Joseph , Beltrame John , Lang Irene , Schuchlenz Herwig , Huber Kurt , Goetschalckx Kaatje , Hueb Whady , Caramori Paulo Ricardo , de Quadros Alexandre , Smanio Paola , Mesquita Claudio , Lopes Renato D. , Vitola João , Marin-Neto José , da Silva Expedito Ribeiro , Tumelero Rogério , Andrade Marianna , Alves Alvaro Rabelo , Dall’Orto Frederico , Polanczyk Carisi , Figueiredo Estevão , Howarth Andrew , Gosselin Gilbert , Cheema Asim , Bainey Kevin , Phaneuf Denis , Diaz Ariel , Garg Pallav , Mehta Shamir , Wong Graham , Lam Andy , Cha James , Galiwango Paul , Uxa Amar , Chow Benjamin (Ben) , Hameed Adnan , Udell Jacob , Cheema Asim , Hamid Magdy , Hauguel-Moreau Marie , Furber Alain , Goube Pascal , Steg Philippe-Gabriel , Barone-Rochette Gilles , Thuaire Christophe , Slama Michel , Doerr Rolf , Nickenig Georg , Bekeredjian Raffi , Schulze P. Christian , Merkely Bela , Fontos Geza , Vértes András , Varga Albert , Bhargava Balram , Kumar Ajit , Nair Rajesh G. , Grant Purvez , Manjunath Cholenahally , Moorthy Nagaraja , Satheesh Santhosh , Nath Ranjit Kumar , Wander Gurpreet , Christopher Johann , Dwivedi Sudhanshu , Oomman Abraham , Mathur Atul , Gadkari Milind , Naik Sudhir , Punnoose Eapen , Kachru Ranjan , Christopher Johann , Kaul Upendra , Sharir Tali , Kerner Arthur , Tarantini Giuseppe , Perna Gian Piero , Racca Emanuela , Mortara Andrea , Monti Lorenzo , Briguori Carlo , Leone Gianpiero , Amati Roberto , Salvatori Mauro , Di Chiara Antonio , Calabro Paolo , Galvani Marcello , Provasoli Stefano , Fukuda Keiichi , Kohsaka Shun , Nakano Shintaro , Laucevicius Aleksandras , Kedev Sasko , Khairuddin Ahmad , Escobedo Jorge , Riezebos Robert , Timmer Jorik , Heald Spencer , Stewart Ralph , Ramos Walter Mogrovejo , Demkow Marcin , Mazurek Tomasz , Drozdz Jarozlaw , Szwed Hanna , Witkowski Adam , Ferreira Nuno , Pinto Fausto , Ramos Ruben , Popescu Bogdan , Pop Calin , Bockeria Leo , Bockeria Olga , Demchenko Elena , Romanov Alexander , Bershtein Leonid , Jizeeri Ahmed , Stankovic Goran , Apostolovic Svetlana , Adjic Nada Cemerlic , Zdravkovic Marija , Beleslin Branko , Dekleva Milica , Davidovic Goran , Chua Terrance , Foo David , Poh Kian Keong , Ntsekhe Mpiko , Sionis Alessandro , Marin Francisco , Miró Vicente , López-Sendón José , Blancas Montserrat Gracida , González-Juanatey José , Fernández-Avilés Francisco , Peteiro Jesús , Luena Jose Enrique Castillo , Held Claes , Aspberg Johannes , Rossi Mariagrazia , Kuanprasert Srun , Yamwong Sukit , Johnston Nicola , Donnelly Patrick , Moriarty Andrew , Senior Roxy , Elghamaz Ahmed , Gurunathan Sothinathan , Karogiannis Nikolaos , Shah Benoy N. , Trimlett Richard H.J. , Rubens Michael B. , Nicol Edward D. , Mittal Tarun K. , Hampson Reinette , Gamma Reto , De Belder Mark , Nageh Thuraia , Lindsay Steven , Mavromatis Kreton , Miller Todd , Banerjee Subhash , Reynolds Harmony , Nour Khaled , Stone Peter 
Published: November 2022

Background:
The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing.

Methods:
ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol.

Results:
Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease.

Conclusions:
There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04894877.