Renato D Lopes1, Karen P Alexander2, Susanna R Stevens2, Harmony R Reynolds3, Gregg W Stone4, Ileana L Piña5, Frank W Rockhold2, Ahmed Elghamaz6, Jose Luis Lopez-Sendon7, Pedro S Farsky8, Alexander M Chernyavskiy9, Ariel Diaz10, Denis Phaneuf11, Mark A De Belder12, Yi-Tong Ma13, Luis A Guzman14, Michel Khouri1, Alessandro Sionis15, Derek J Hausenloy16,17,18,19,20, Rolf Doerr21, Joseph B Selvanayagam22, Aldo Pietro Maggioni23, Judith S Hochman3, David J Maron24. 1. Duke University Medical Center, Durham, NC (R.D.L., M.K.). 2. Duke Clinical Research Institute, Durham, NC (K.P.A., S.R.S., F.W.R.). 3. NYU Grossman School of Medicine, New York (H.R.R., J.S.H.). 4. Icahn School of Medicine at Mount Sinai, Cardiovascular Research Foundation, New York (G.W.S.). 5. Wayne State University/Central Michigan University, Detroit (I.L.P.). 6. Northwick Park Hospital-Royal Brompton Hospital, London, UK (A.E.). 7. Hospital Universitario La Paz, IdiPaz, CIBER-CV, Madrid, Spain (J.L.L.-S.). 8. Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil (P.S.F.). 9. E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Moscow, Russia (A.M.C.). 10. CIUSSS-MCQ, University of Montreal, Campus Mauricie, Trois-Rivieres, Canada (A.D.). 11. Hôpital Pierre-Le Gardeur, Quebec, Canada (D.P.). 12. Barts Health NHS Trust, London, UK (M.A.D.). 13. First Affiliated Hospital of Xinjiang Medical University, Urumqi, China (Y.-t.M.). 14. DAMIC Medical Institute, Cordoba, Argentina (L.A.G.). 15. Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, CIBER-CV, Universitat Autònoma de Barcelona, Spain (A.S.). 16. The Hatter Cardiovascular Institute, Institute of Cardiovascular Sciences, University College London, UK (D.J.H.). 17. Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School (D.J.H.). 18. National Heart Research Institute Singapore, National Heart Centre (D.J.H.). 19. Yong Loo Lin School of Medicine, National University Singapore (D.J.H.). 20. Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taiwan (D.J.H.). 21. Praxisklinik Herz und Gefaesse, Dresden, Germany (R.D.). 22. Flinders Medical Centre, Adelaide, Australia (J.B.S.). 23. ANMCO Research Center, Florence, Italy (A.P.M.). 24. Department of Medicine, Stanford University School of Medicine, CA (D.J.M.).
Abstract
BACKGROUND: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown. METHODS: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. RESULTS: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. CONCLUSIONS: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
BACKGROUND: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown. METHODS: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. RESULTS: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. CONCLUSIONS: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
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