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1. Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management

Author

Andreas B Gevaert, Rachna Kataria, Faiez Zannad, Andrew J Sauer, Kevin Damman, Kavita Sharma, Sanjiv J Shah, Harriette G C Van Spall, Universiteit Antwerpen = University of Antwerpen [Antwerpen], Antwerp University Hospital [Edegem] (UZA), University Medical Center Groningen [Groningen] (UMCG), Massachusetts General Hospital [Boston, MA, USA], Harvard Medical School [Boston] (HMS), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Kansas [Kansas City], Johns Hopkins University School of Medicine [Baltimore], Bluhm Cardiovascular Institute at Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University [Evanston], McMaster University [Hamilton, Ontario], Population Health Research Institute, McMaster University [Hamilton, Ontario]-Hamilton General Hospital, ABG acknowledges funding from the European Society of Cardiology in form of an ESC Training Grant. SJS has received research grants from the National Institutes of Health (R01 HL107577, R01 HL127028, R01 HL140731, R01 HL149423). HGCV is funded by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada, and BOZEC, Erwan

Subjects
Heart Failure, Ventricular Dysfunction, Left, Angiotensins, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiovascular system, Humans, Stroke Volume, Human medicine, Cardiology and Cardiovascular Medicine, Prognosis, Biology, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

International audience; It is estimated that half of all patients with heart failure (HF) have HF with preserved ejection fraction (HFpEF). Yet this form of HF remains a diagnostic and therapeutic challenge. Differentiating HFpEF from other causes of dyspnoea may require advanced diagnostic methods, such as exercise echocardiography, invasive haemodynamics and investigations for ‘HFpEF mimickers’. While the classification of HF has relied heavily on cut-points in left ventricular ejection fraction (LVEF), recent evidence points towards a gradual shift in underlying mechanisms, phenotypes and response to therapies as LVEF increases. For example, among patients with HF, the proportion of hospitalisations and deaths due to cardiac causes decreases as LVEF increases. Medication classes that are efficacious in HF with reduced ejection fraction (HFrEF) have been less so at higher LVEF ranges, decreasing the risk of HF hospitalisation but not cardiovascular or all-cause death in HFpEF. These observations reflect the burden of non-cardiac comorbidities as LVEF increases and highlight the complex pathophysiological mechanisms, both cardiac and non-cardiac, underpinning HFpEF. Treatment with sodium-glucose cotransporter 2 inhibitors reduces the risk of composite cardiovascular events, driven by a reduction in HF hospitalisations; renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors result in smaller reductions in HF hospitalisations among patients with HFpEF. Comprehensive management of HFpEF includes exercise as well as treatment of risk factors and comorbidities. Classification based on phenotypes may facilitate a more targeted approach to treatment than LVEF categorisation, which sets arbitrary cut-points when LVEF is a continuum. This narrative review summarises the pathophysiology, diagnosis, classification and management of patients with HFpEF.

Published
2021
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2. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke

Author

Sacco, Rl, Diener, Hc, Yusuf, S, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlöf, B, DE KEYSER, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, Danilo, Vandermaelen, C, Voigt, T, Weber, M, Yoon, Bw, Lembo, Giuseppe, Rasura, Maurizia, Sacchetti, Maria Luisa, Faculteit Medische Wetenschappen/UMCG, Gerontology, Department of neurology, University of Miami Leonard M. Miller School of Medicine (UMMSM)-University of Miami [Coral Gables], Universität Duisburg-Essen [Essen], Boehringer Ingelheim GmbH, Boehringer Ingelheim Pharmaceuticals, Population Health Research Institute, McMaster University [Hamilton, Ontario]-Hamilton General Hospital, Boehringer Ingelheim, Boehringer Ingelheim Ltd, Department of biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina [Charleston] (MUSC), Neurology and Neurological Sciences, Stanford University, Stroke Trials Unit, University of Nottingham, UK (UON), Neurology Department, Ichilov Medical Center, Division of Neurology, Department of Medicine, National University Hospital Singapore, Department of Neurology, Chang Gung Memorial Hospital [Taipei] (CGMH), Neurology department, Universidade de Coimbra [Coimbra], Institute of Medicine, Sahlgrenska University Hospital [Gothenburg], University Medical Center Groningen [Groningen] (UMCG), National Stroke Research Institute, University of Melbourne, Neurological Center for Treatment and Research, Department of Neurology and Rehabilitation, University of Illinois System, Boehringer Ingelheim Shanghai Pharmaceuticals Co Ltd, Boehringer Ingelheim AB, Helsinki University Central Hospital, Huashan Hospital [Shangai], Saint John's Medical College, Clinical Trials Methodoloy Group, McMaster University [Hamilton, Ontario], Neurology & Neurosurgery Clinic, Russian State Medical University, Department of Medicine, Neurology, Faculty of Medicine, University of British Columbia (UBC), Department of Neurological Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Cardiology Department, SUNY Downstate Medical Center, State University of New York (SUNY)-State University of New York (SUNY), Seoul National University Hospital, Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Sacco, Rl, Diener, Hc, Yusuf, S, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlof, B, DE KEYSER, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, D, Vandermaelen, C, Voigt, T, Weberm, Yoon, Bw, and Comi, Giancarlo

Subjects
Male, Myocardial Infarction, Angiotensin-Converting Enzyme Inhibitors, MESH: Cognition, Brain Ischemia, NON-INFERIORITY TRIALS, 0302 clinical medicine, aspirina, Secondary Prevention, Aspirin, MESH: Middle Aged, MESH: Risk, Hazard ratio, MESH: Disability Evaluation, MESH: Brain Ischemia, Dipyridamole, MESH: Follow-Up Studies, ARTERIAL ORIGIN ESPRIT, General Medicine, RANDOMIZED CONTROLLED-TRIAL, 3. Good health, MESH: Myocardial Infarction, Platelet aggregation inhibitor, Drug Therapy, Combination, MESH: Hemorrhage, medicine.medical_specialty, MESH: Ticlopidine, MESH: Delayed-Action Preparations, MESH: Drug Delivery Systems, MESH: Factor Analysis, Statistical, Hemorrhage, MESH: Drug Administration Schedule, MESH: Stroke, 03 medical and health sciences, MESH: Severity of Illness Index, Humans, Vascular Diseases, ACTIVE CONTROLLED-TRIALS, MESH: Kaplan-Meier Estimate, Aged, ictus, trial clinico, MESH: Humans, Proportional hazards model, MESH: Angiotensin II Type 1 Receptor Blockers, MESH: Retrospective Studies, medicine.disease, MESH: Benzoates, PREVENTION, MESH: International Cooperation, Delayed-Action Preparations, Benzimidazoles, Factor Analysis, Statistical, MESH: Mental Status Schedule, MESH: Female, 030217 neurology & neurosurgery, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Benzoates, MESH: Proportional Hazards Models, DOUBLE-BLIND, MESH: Double-Blind Method, Telmisartan, Stroke, MESH: Aged, MESH: Angiotensin-Converting Enzyme Inhibitors, Middle Aged, Clopidogrel, MESH: Platelet Aggregation Inhibitors, Anesthesia, MESH: Vascular Diseases, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, Risk, Double-Blind Method, TICLOPIDINE, Internal medicine, medicine, cardiovascular diseases, MESH: Aspirin, Ticlopidine, HIGH-RISK PATIENTS, Proportional Hazards Models, CEREBRAL-ISCHEMIA, business.industry, MESH: Male, MESH: Recurrence, MESH: Drug Therapy, Combination, TRANSIENT ISCHEMIC ATTACK, MESH: Dipyridamole, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Benzimidazoles, business, Platelet Aggregation Inhibitors
Abstract

Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial; International audience; BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Published
2008
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3. Telmisartan to prevent recurrent stroke and cardiovascular events

Author

Yusuf, S, Diener, Hc, Sacco, Rl, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlöf, B, DE KEYSER, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, Danilo, Vandermaelen, C, Voigt, T, Weber, M, Yoon, Bw, Lembo, Giuseppe, Rasura, Maurizia, Sacchetti, Maria Luisa, Hamilton General Hospital, Population Health Research Institute, McMaster University [Hamilton, Ontario]-Hamilton General Hospital, Universität Duisburg-Essen [Essen], Miller School of Medicine, University of Miami [Coral Gables], Institute of Medicine, Sahlgrenska University Hospital, Helsinki University, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Neuroépidémiologie Tropicale et Comparée ( NETEC ), Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges ( UNILIM ), Service de Neurologie [CHU Limoges], CHU Limoges, University of Miami Leonard M. Miller School of Medicine (UMMSM), Sahlgrenska University Hospital [Gothenburg], University of Helsinki, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Yusuf, S, Diener, Hc, Sacco, Rl, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlof, B, De Keyser, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, D, Vandermaelen, C, Voigt, T, Weber, M, Yoon, Bw, Comi, Giancarlo, PRoFESS Stuy, Group, Gerontology, and Faculteit Medische Wetenschappen/UMCG

Subjects
Male, MESH: Treatment Failure, MESH : Recurrence, Myocardial Infarction, MESH : Aged, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, BLOOD-PRESSURE, 0302 clinical medicine, DESIGN, Secondary Prevention, MESH : Cardiovascular Diseases, Myocardial infarction, MESH: Middle Aged, Hazard ratio, General Medicine, MESH: Follow-Up Studies, MESH: Blood Pressure, 3. Good health, MESH: Myocardial Infarction, MESH : Diabetes Mellitus, Cardiovascular Diseases, Creatinine, MESH : Angiotensin-Converting Enzyme Inhibitors, Ramipril, medicine.medical_specialty, MESH: Diabetes Mellitus, MESH: Creatinine, [ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Article, MESH: Stroke, 03 medical and health sciences, MESH : Treatment Failure, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes Mellitus, Humans, MESH : Middle Aged, COMBINATION, MESH: Kaplan-Meier Estimate, Aged, Heart Failure, MESH: Humans, VASCULAR EVENTS, MORTALITY, MESH : Humans, MESH : Creatinine, MESH: Cardiovascular Diseases, MESH : Follow-Up Studies, medicine.disease, MESH: Benzoates, RAMIPRIL, Blood pressure, MESH : Potassium, Potassium, Benzimidazoles, MESH : Heart Failure, MESH: Female, 030217 neurology & neurosurgery, MESH : Stroke, RATIONALE, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Benzoates, RANDOMIZED TRIAL, DOUBLE-BLIND, MESH : Female, sartani, ictus, trial clinico, Telmisartan, Treatment Failure, Stroke, MESH: Aged, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MESH: Angiotensin-Converting Enzyme Inhibitors, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Benzimidazoles, Cardiology, Female, medicine.drug, MESH : Benzoates, MESH : Male, MESH : Kaplan-Meier Estimate, Internal medicine, Diabetes mellitus, medicine, MESH : Blood Pressure, HIGH-RISK PATIENTS, business.industry, Angiotensin II, MESH: Male, Surgery, MESH: Recurrence, MESH: Heart Failure, MESH: Potassium, MESH : Myocardial Infarction, business, MESH: Benzimidazoles, Follow-Up Studies
Abstract

Background: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.Methods: In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.Results: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).Conclusions: Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.).

Published
2008
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