TY - JOUR
T1 - New strategies for heart failure with preserved ejection fraction
T2 - The importance of targeted therapies for heart failure phenotypes
AU - Senni, Michele
AU - Paulus, Walter J.
AU - Gavazzi, Antonello
AU - Fraser, Alan G.
AU - Díez, Javier
AU - Solomon, Scott D.
AU - Smiseth, Otto A.
AU - Guazzi, Marco
AU - Lam, Carolyn S P
AU - Maggioni, Aldo P.
AU - Tschöpe, Carsten
AU - Metra, Marco
AU - Hummel, Scott L.
AU - Edelmann, Frank
AU - Ambrosio, Giuseppe
AU - Coats, Andrew J Stewart
AU - Filippatos, Gerasimos S.
AU - Gheorghiade, Mihai
AU - Anker, Stefan D.
AU - Levy, Daniel
AU - Pfeffer, Marc A.
AU - Stough, Wendy Gattis
AU - Pieske, Burkert M.
PY - 2014/10/21
Y1 - 2014/10/21
N2 - The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.
AB - The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.
KW - Clinical trial
KW - Diabetes mellitus
KW - Exercise tolerance
KW - Heart failure, Diastolic
KW - Phenotype
KW - Preserved ejection fraction
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U2 - 10.1093/eurheartj/ehu204
DO - 10.1093/eurheartj/ehu204
M3 - Article
C2 - 25104786
AN - SCOPUS:84920261725
VL - 35
SP - 2797-2811d
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 40
ER -