beta-blockers; heart failure with reduced ejection fraction; mineralocorticoid-receptor antagonists; randomized controlled trial; renin-angiotensin-aldosterone inhibitors; stroke; Cardiology and Cardiovascular Medicine
Résumé :
[en] [en] BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) have a heightened stroke risk. However, stroke as an endpoint in heart failure trials remains under-reported.
OBJECTIVES: The authors sought to define the incidence, characteristics, predictors, modifier treatments, and prognostic impact of stroke in patients with HFrEF who were enrolled in randomized controlled trials (RCTs).
METHODS: The authors systematically reviewed MEDLINE for RCTs of pharmacologic and nonpharmacologic treatments in HFrEF. The annualized stroke incidence was the primary outcome. Subgroup analyses and meta-regressions were performed to determine the baseline modulating characteristics and to assess the association of stroke with other clinical outcomes.
RESULTS: Of 7,104 records, 188 RCTs fulfilled inclusion criteria for the systematic review. Of these, 158 studies (84.0%) did not report stroke outcomes and were excluded from the meta-analysis, leading to a final cohort of 30 studies, with 61 arms and 75,327 patients. Stroke incidence was 1.1% (95% CI: 0.9%-1.3%; I2: 74%) with high heterogeneity across trials. Higher NYHA functional class (P < 0.001), lower systolic blood pressure (P < 0.001), diuretic use (P = 0.001), and diabetes (P < 0.001) were associated with stroke. No association of renin-angiotensin-aldosterone inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and transcatheter mitral valve replacement with stroke was observed. Stroke was associated with higher risk of all-cause and cardiovascular mortality, heart failure hospitalization and acute coronary syndromes (P < 0.001 for all).
CONCLUSIONS: Stroke was reported in a vast minority of HFrEF RCTs with heterogeneous definitions and no reference to underlying mechanisms. Despite under-reporting, stroke incidence is non-negligible. Stroke is associated with HFrEF-specific characteristics and outcomes, whereas it is not impacted by current HFrEF treatments. There is a need for dedicated research into preventive strategies and effective treatments to address this debilitating and deadly comorbidity. (Stroke Events in Heart Failure With Reduced Ejection Fraction-A Systematic Review and Meta-Analysis of Pharmacologic Randomized Trial; CRD42023418422).
Disciplines :
Systèmes cardiovasculaire & respiratoire
Auteur, co-auteur :
Gallone, Guglielmo; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy. Electronic address: guglielmo.gallone@gmail.com
Savoca, Federica; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy
Miccoli, Davide; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy
Böhm, Michael; Clinic III for Internal Medicine (Cardiology, Angiology, and Intensive Care Medicine) Saarland University, Homburg/Saar, Germany
De Ferrari, Gaetano Maria ; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy
Gottlieb, Stephen S; Division of Cardiovascular Medicine, University of Maryland School of Medicine and Baltimore, Veterans Administration Medical Center, Baltimore, Maryland, USA
Lancellotti, Patrizio ; Université de Liège - ULiège > Département des sciences cliniques > Cardiologie - Pathologie spéciale et réhabilitation
Lindenfeld, JoAnn; Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Saldarriaga, Clara; CardioVID Clinic, University of Antioquia, Medellín, Colombia
Samad, Zainab ; The Aga Khan University, Karachi, Pakistan
Teerlink, John R; Section of Cardiology, San Francisco Veterans Affairs Medical Center, School of Medicine, University of California San Francisco, San Francisco, California, USA
Savarese, Gianluigi ; Department of Clinical Science, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
Ammirati, Enrico ; De Gasperis Cardio Center, Transplant Center, Niguarda Hospital, Milano, Italy, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy
Scheitz, J.F., Nolte, C.H., Doehner, W., Hachinski, V., Endres, M., Stroke–heart syndrome: clinical presentation and underlying mechanisms. Lancet Neurol 17:12 (2018), 1109–1120, 10.1016/S1474-4422(18)30336-3.
Havakuk, O., King, K.S., Grazette, L., et al. Heart failure–induced brain injury. J Am Coll Cardiol 69:12 (2017), 1609–1616.
Doehner, W., Böhm, M., Boriani, G., et al. Interaction of heart failure and stroke: a clinical consensus statement of the ESC Council on Stroke, the Heart Failure Association (HFA) and the ESC Working Group on Thrombosis. Eur J Heart Fail 25:12 (2023), 2107–2129, 10.1002/ejhf.3071.
Pullicino, P.M., McClure, L.A., Wadley, V.G., et al. Blood pressure and stroke in heart failure in the reasons for geographic and racial differences in stroke (regards) study. Stroke 40:12 (2009), 3706–3710, 10.1161/STROKEAHA.109.561670.
Witt, B.J., Brown, R.D., Jacobsen, S.J., et al. Ischemic stroke after heart failure: a community-based study. Am Heart J 152:1 (2006), 102–109, 10.1016/j.ahj.2005.10.018.
Haeusler, K.G., Laufs, U., Endres, M., Chronic heart failure and ischemic stroke. Stroke 42:10 (2011), 2977–2982, 10.1161/STROKEAHA.111.628479.
Lip, G.Y.H., Ponikowski, P., Andreotti, F., et al. Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm. A Joint Consensus Document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Eur J Heart Fail 14:7 (2012), 681–695, 10.1093/eurjhf/hfs073.
Liberati, A., Altman, D.G., Tetzlaff, J., et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ, 339(b2700), 2009, 10.1136/bmj.b2700.
Tang, J.L., Ly Liu, J., Misleading funnel plot for detection of bias in meta-analysis. J Clin Epidemiol 53:5 (2000), 477–484.
Timmis, A., Vardas, P., Townsend, N., et al. European Society of Cardiology: cardiovascular disease statistics 2021: executive summary. Eur Heart J Qual Care Clin Outcomes 8:4 (2022), 377–382, 10.1093/ehjqcco/qcac014.
Lip, G.Y.H., Lane, D.A., Lenarczyk, R., et al. Integrated care for optimizing the management of stroke and associated heart disease: a position paper of the European Society of Cardiology Council on Stroke. Eur Heart J 43:26 (2022), 2442–2460, 10.1093/eurheartj/ehac245.
Virani, S.S., Alonso, A., Aparicio, H.J., et al. Heart disease and stroke statistics—2021 update: a report from the American Heart Association. Circulation 143:8 (2021), E254–E743, 10.1161/CIR.0000000000000950.
Li, C., Engstrom, G., Hedblad, B., Berglund, G., Janzon, L., Blood pressure control and risk of stroke: a population-based prospective cohort study. Stroke 36:4 (2005), 725–730, 10.1161/01.STR.0000158925.12740.87.
Khoury, J.C., Kleindorfer, D., Alwell, K., et al. Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population. Stroke 44:6 (2013), 1500–1504, 10.1161/STROKEAHA.113.001318.
Adelborg, K., Szépligeti, S., Sundbøll, J., et al. Risk of stroke in patients with heart failure: a population-based 30-year cohort study. Stroke 48:5 (2017), 1161–1168, 10.1161/STROKEAHA.116.016022.
Alberts, V.P., Bos, M.J., Koudstaal, P.J., et al. Heart failure and the risk of stroke: the Rotterdam Study. Eur J Epidemiol 25:11 (2010), 807–812, 10.1007/s10654-010-9520-y.
Pullicino, P.M., Halperin, J.L., Thompson, J.L.P., Stroke in patients with heart failure and reduced left ventricular ejection fraction. Neurology, 52(2), 2000 288-288.
Sagris, D., Shantsila, E., Lip, G.Y.H., Stroke risk stratification in patients with heart failure and sinus rhythm. Eur Heart J 43:42 (2022), 4480–4482, 10.1093/eurheartj/ehac493.
Mogensen, U.M., Jhund, P.S., Abraham, W.T., et al. Type of atrial fibrillation and outcomes in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 70:20 (2017), 2490–2500.
Swedberg, K., Olsson, L.G., Charlesworth, A., et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J 26:13 (2005), 1303–1308, 10.1093/eurheartj/ehi166.
Zannad, F., Anker, S.D., Byra, W.M., et al. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. N Engl J Med 379:14 (2018), 1332–1342, 10.1056/nejmoa1808848.
Homma, S., Thompson, J.L.P., Pullicino, P.M., et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 366:20 (2012), 1859–1869, 10.1056/nejmoa1202299.
Teerlink, J.R., Diaz, R., Felker, G.M., et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med 384:2 (2021), 105–116, 10.1056/nejmoa2025797.
Page, M.J., McKenzie, J.E., Bossuyt, P.M., et al. The PRISMA 2020 statement: an updated guideline for reporting systemic reviews. BMJ, 372, 2021, n71, 10.1136/bnj.n71.
