Jose L Lopez-Sendon1, Derek D Cyr2, Daniel B Mark2, Sripal Bangalore3, Zhen Huang2, Harvey D White4, Karen P Alexander2, Jianghao Li2, Rajesh Goplan Nair5, Marcin Demkow6, Jesus Peteiro7, Gurpreet S Wander8, Elena A Demchenko9, Reto Gamma10, Milind Gadkari11, Kian Keong Poh12,13, Thuraia Nageh14, Peter H Stone15, Matyas Keltai16, Mandeep Sidhu17, Jonathan D Newman3, William E Boden18, Harmony R Reynolds3, Bernard R Chaitman19, Judith S Hochman3, David J Maron20, Sean M O'Brien2. 1. Cardiology department, Hospital Universitario La Paz, Idipaz, UAM, CIBER-CV, Paseo de la Castellana 261, Madrid 28046, Spain. 2. Duke Clinical Research Institute and Duke University, 300 W. Morgan Street, Durham, NC, USA. 3. NYU Grossman School of Medicine, 530 First Avenue, New York, NY, USA. 4. Auckland City Hospital Green Lane Cardiovascular Services and University of Auckland, 2 Park Road, Grafton, Auckland 1023, New Zealand. 5. Government Medical College, 48/584, Subhag Sastrinagar, Thiruvananthapuram, Kerala 695002, India. 6. Department of Coronary and Structural Heart Diseases, National Institute of Cardiology, Alpejska 42, Warsaw 04-628, Poland. 7. CHUAC, Universidad de A Coruña, CIBER-CV, As Xubias, 84, A Coruna 15006, Spain. 8. Dayanand Medical College & Hospital, Civil Lines, Tagore Nagar, Ludhiana, Punjab 141001, India. 9. Almazov National Medical Research Centre, Ulitsa Akkuratova, 2, Saint-Petersburg 197341, Russia. 10. Broomfield Hospital, Court Rd, Broomfield, Chelmsford CM1 7ET, UK. 11. Kem Hospital Maharashtra, 489, Mudaliar Rd, Rasta Peth, Pune, Maharashtra 411011, India. 12. National University Heart Center Singapore, Singapore, Singapore. 13. Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, Singapore. 14. Southend University Hospital, Prittlewell Chase, Westcliff-on-Sea, Southend-on-Sea, Westcliff-on-Sea SS0 0RY, Southend, England, UK. 15. Brigham and Women's Hospital, 75 Francis St, Boston, MA, USA. 16. Semmelweis University, Budapest, Üllői út 26, 1085 Hungary. 17. Albany Medical College, 47 New Scotland Avenue, Physicians Pavilion, 2nd Floor, Albany, NY 12208, USA. 18. VA New England Healthcare System, Boston University School of Medicine, 150 South Huntington Avenue, Boston, MA, USA. 19. St Louis University School of Medicine Center for Comprehensive Cardiovascular Care, 1034 S. Brentwood Blvd., Suite 1120, St. Louis, MO, USA. 20. Department of Medicine, Stanford University, 300 Pasteur Drive, Falk CVRC 265, Stanford, CA 94305-5406, USA.
Abstract
AIMS: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. METHODS AND RESULTS: Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh-Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8-20.9] and 19.7 in CON (95% CI 17.5-22.2), difference -1.5 (95% CI -5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. CONCLUSIONS: In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. CLINICAL TRIAL REGISTRATION: ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. METHODS AND RESULTS: Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh-Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8-20.9] and 19.7 in CON (95% CI 17.5-22.2), difference -1.5 (95% CI -5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. CONCLUSIONS: In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. CLINICAL TRIAL REGISTRATION: ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522. Published on behalf of the European Society of Cardiology. All rights reserved.