João Pedro Ferreira1,2,3, John G Cleland4, Carolyn S P Lam5,6, Stefan D Anker7,8, Mandeep R Mehra9, Dirk J van Veldhuisen6, William M Byra10, David A La Police10, Bertram Pitt11, Barry Greenberg12, Faiez Zannad13,14,15. 1. Centre d'investigations Cliniques Plurithématique, Inserm 1433, Université de Lorraine, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, CHRU Nancy-Hopitaux de Brabois, 4 rue du Morvan, 54500, Nancy, Vandoeuvre les Nancy, France. j.ferreira@chru-nancy.fr. 2. CHRU de Nancy, Inserm U1116, Nancy, France. j.ferreira@chru-nancy.fr. 3. FCRIN INI-CRCT, Nancy, France. j.ferreira@chru-nancy.fr. 4. Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, Scotland. 5. National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore. 6. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 7. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany. 8. Department of Cardiology, German Center for Cardiovascular Research Partner Site Berlin, Charite Universitatsmedizin Berlin, Berlin, Germany. 9. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 10. Janssen Research and Development, Raritan, NJ, USA. 11. Department of Medicine, University of Michigan School of Medicine, Ann Arbor, USA. 12. Cardiology Division, Department of Medicine, University of California, La Jolla, San Diego, USA. 13. Centre d'investigations Cliniques Plurithématique, Inserm 1433, Université de Lorraine, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, CHRU Nancy-Hopitaux de Brabois, 4 rue du Morvan, 54500, Nancy, Vandoeuvre les Nancy, France. f.zannad@chru-nancy.fr. 14. CHRU de Nancy, Inserm U1116, Nancy, France. f.zannad@chru-nancy.fr. 15. FCRIN INI-CRCT, Nancy, France. f.zannad@chru-nancy.fr.
Abstract
BACKGROUND: Patients with coronary artery disease (CAD) are at increased risk of developing and being hospitalised for heart failure (HFH). However, the risk of HFH versus ischemic events may vary among patients with CAD, depending on whether acute myocardial infarction (MI), left ventricular dysfunction or decompensated HF is present at baseline. AIMS: We aim to explore the risk of non-fatal events (HFH, MI, stroke) and subsequent death in 3 landmark trials, COMMANDER-HF, EPHESUS and EXAMINE that, together, included patients with CAD with and without reduced ejection fraction and acute MI. METHODS: Events, person-time metrics and time-updated Cox models. RESULTS: In COMMANDER-HF the event-rate for the composite of AMI, stroke or all-cause death was 13.5 (12.8-14.3) events/100 py. Rates for AMI and stroke were much lower (2.2 [2.0-2.6] and 1.3 [1.1-1.6] events/100 py, respectively) than the rate of HFH (16.9 [16.1-17.9] events/100 py). In EPHESUS, the rates of MI and stroke were also lower than the rate of HFH: 7.2 (6.7-7.8), 1.9 (1.7-2.3), and 10.6 (9.9-11.3) events/100 py, but this was not true for EXAMINE with 4.4 (4.0-4.9), 0.7 (0.6-0.9), and 2.4 (2.0-2.7) events/100 py, respectively. In all 3 trials, a non-fatal event (HFH, MI or stroke) during follow-up doubled the risk of subsequent mortality. This most commonly followed a HFH. CONCLUSIONS: A first or recurrent HFH is common in patients with CAD and AMI or HFrEF and indicates a poor prognosis. Preventing the development of heart failure after AMI and control of congestion in patients with CAD and HFrEF are key unmet needs and therapeutic targets. REGISTRATION: ClinicalTrials.gov Identifier: NCT01877915. URL: https://clinicaltrials.gov/ct2/show/NCT01877915 .
BACKGROUND: Patients with coronary artery disease (CAD) are at increased risk of developing and being hospitalised for heart failure (HFH). However, the risk of HFH versus ischemic events may vary among patients with CAD, depending on whether acute myocardial infarction (MI), left ventricular dysfunction or decompensated HF is present at baseline. AIMS: We aim to explore the risk of non-fatal events (HFH, MI, stroke) and subsequent death in 3 landmark trials, COMMANDER-HF, EPHESUS and EXAMINE that, together, included patients with CAD with and without reduced ejection fraction and acute MI. METHODS: Events, person-time metrics and time-updated Cox models. RESULTS: In COMMANDER-HF the event-rate for the composite of AMI, stroke or all-cause death was 13.5 (12.8-14.3) events/100 py. Rates for AMI and stroke were much lower (2.2 [2.0-2.6] and 1.3 [1.1-1.6] events/100 py, respectively) than the rate of HFH (16.9 [16.1-17.9] events/100 py). In EPHESUS, the rates of MI and stroke were also lower than the rate of HFH: 7.2 (6.7-7.8), 1.9 (1.7-2.3), and 10.6 (9.9-11.3) events/100 py, but this was not true for EXAMINE with 4.4 (4.0-4.9), 0.7 (0.6-0.9), and 2.4 (2.0-2.7) events/100 py, respectively. In all 3 trials, a non-fatal event (HFH, MI or stroke) during follow-up doubled the risk of subsequent mortality. This most commonly followed a HFH. CONCLUSIONS: A first or recurrent HFH is common in patients with CAD and AMI or HFrEF and indicates a poor prognosis. Preventing the development of heart failure after AMI and control of congestion in patients with CAD and HFrEF are key unmet needs and therapeutic targets. REGISTRATION: ClinicalTrials.gov Identifier: NCT01877915. URL: https://clinicaltrials.gov/ct2/show/NCT01877915 .