Survival After Invasive or Conservative Management of Stable Coronary Disease
Judith S. Hochman, Rebecca Anthopolos, Harmony R. Reynolds, Sripal Bangalore, Yifan Xu, Sean M. O’Brien, Stavroula Mavromichalis, Michelle Chang, Aira Contreras, Yves Rosenberg, Ruth Kirby, Balram Bhargava, Roxy Senior, Ann Banfield, Shaun G. Goodman, Renato D. Lópes, Radosław Pracoń, José López‐Sendón, Aldo P. Maggioni, Jonathan Newman, Jeffrey S. Berger, Mandeep S. Sidhu, Harvey D. White, Andrea B. Troxel, Robert A. Harrington, William E. Boden, Gregg W. Stone, Daniel B. Mark, John A. Spertus, David J. Maron, Judith S. Hochman, David J. Maron, Harmony R. Reynolds, Sripal Bangalore, Stavroula Mavromichalis, Michelle Chang, Aira Contreras, Shari Esquenazi‐Karonika, Margaret Gilsenan, Ewelina Gwiszcz, Patenne D. Mathews, Samaa Mohamed, Anna K. Naumova, Arline Roberts, Kerrie VanLoo, Rebecca Anthopolos, Yifan Xu, Andrea B. Troxel, Ying Lü, Zhen Huang, Samuel Broderick, Luis A. Guzmán, Joseph B. Selvanayagam, Renato D. Lópes, Shaun G. Goodman, Gabriel Steg, Jean‐Michel Juliard, Rolf Doerr, Mátyás Keltai, Balram Bhargava, Boban Thomas, Tali Sharir, Eugenia Nikolsky, Aldo P. Maggioni, Shun Kohsaka, Jorge Escobedo, Harvey D. White, Radosław Pracoń, O.L. Bockeria, José López‐Sendón, Claes Held, Roxy Senior, Ann Banfield, Leslee J. Shaw, Lawrence M. Phillips, Daniel S. Berman, Raymond Y. Kwong, Michael H. Picard, Bernard Chaitman, Ziad A. Ali, James K. Min, G.B. John Mancini, Jonathon Leipsic, Luis A. Guzmán, Graham S. Hillis, S. Thambar, Majo Joseph, Joseph B. Selvanayagam, John F. Beltrame, Iréne Lang, Herwig Schuchlenz, Kurt Huber, Kaatje Goetschalckx, Whady Hueb, Paulo Caramori, Alexandre de Quadros, Paola Smanio, Cláudio Tinoco Mesquita, Renato D. Lópes, João V. Vítola
Abstract
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.