Mandeep S Sidhu1, Karen P Alexander2, Zhen Huang2, Sean M O'Brien2, Bernard R Chaitman3, Gregg W Stone4, Jonathan D Newman5, William E Boden6, Aldo P Maggioni7, Philippe Gabriel Steg8, Thomas B Ferguson9, Marcin Demkow10, Jesus Peteiro11, Gurpreet S Wander12, Denis C Phaneuf13, Mark A De Belder14, Rolf Doerr15, Erick Alexanderson-Rosas16, Carisi A Polanczyk17, Peter A Henriksen18, Dwayne S G Conway19, Vicente Miro20, Tali Sharir21, Renato D Lopes2, James K Min22, Daniel S Berman23, Frank W Rockhold2, Stephen Balter24, David Borrego25, Yves D Rosenberg26, Sripal Bangalore5, Harmony R Reynolds5, Judith S Hochman5, David J Maron27. 1. Albany Medical College, Albany, NY. Electronic address: sidhum@amc.edu. 2. Duke Clinical Research Institute - Duke University Medical Center, Durham, NC. 3. St Louis University School of Medicine Center for Comprehensive Cardiovascular Care, St. Louis, MO. 4. Icahn School of Medicine at Mount Sinai, Cardiovascular Research Foundation, New York, NY. 5. NYU Grossman School of Medicine, New York, NY. 6. VA New England Healthcare System, Boston University School of Medicine, Boston, MA. 7. ANMCO Research Center, Florence, Italy. 8. Université de Paris, Assistance Publique-Hôpitaux de Paris, INSERM-1148, Paris, France. 9. Brody School of Medicine, East Carolina University, Greenville, NC, USA. 10. Dept of Coronary and Structural Heart Diseases, National Institute of Cardiology, Warsaw, Poland. 11. CHUAC, Universidad de A Coruña, CIBER-CV, A Coruña, Spain. 12. Dayanand Medical College & Hospital, Ludhiana, Punjab, India. 13. Hôpital Pierre-Le Gardeur, Quebec, Terrebonne, Canada. 14. Barts Health NHS Trust, London, United Kingdom. 15. Praxisklinik Herz und Gefaesse, Dresden, Germany. 16. Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico. 17. Federal University of Rio Grande do Sul, Hospital Clínicas de Porto Alegre, Porto Alegre, Brazil. 18. Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. 19. Northern General Hospital, Sheffield, United Kingdom. 20. Hospital universitario y politecnico La Fe, Valencia, Spain. 21. Assuta Medical Center and Ben Gurion University of the Negev, Tel Aviv, Israel. 22. Cleerly, Inc. New York, NY. 23. Cedars-Sinai Medical Center, Los Angeles, CA. 24. Columbia University, New York, NY. 25. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. 26. National Institute of Health- NHLBI, Bethesda, MD. 27. Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Abstract
BACKGROUND: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. METHODS: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. RESULTS: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy. CONCLUSIONS: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.
BACKGROUND: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. METHODS: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. RESULTS: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy. CONCLUSIONS: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.
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