The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Brian Claggett - One of the best experts on this subject based on the ideXlab platform.
-
spironolactone in patients with heart failure preserved ejection fraction and worsening renal function
Journal of the American College of Cardiology, 2021Co-Authors: Iris E Beldhuis, Brian Claggett, Jerome L Fleg, Eldrin F Lewis, James C Fang, Sonja M Mckinlay, Peder L Myhre, Michael R Bristow, Kevin Damman, Eileen OmearaAbstract:Abstract Background Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood. Objectives The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF. Methods In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term. Results WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p Conclusions Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF.
-
influence of age on efficacy and safety of spironolactone in heart failure
Jacc-Heart Failure, 2019Co-Authors: Orly Vardeny, Brian Claggett, Sanjiv J Shah, Inder S Anand, Eileen Omeara, Muthiah Vaduganathan, Iris E Beldhuis, Jean L Rouleau, Nancy K SweitzerAbstract:Abstract Objectives The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Background Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. Methods TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories ( Results The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p Conclusions In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302 )
-
the frailty syndrome and outcomes in the topcat trial
European Journal of Heart Failure, 2018Co-Authors: Natalie A Sanders, Scott D Solomon, Brian Claggett, Akshay S. Desai, Nancy K Sweitzer, Marc A Pfeffer, Eldrin F Lewis, Jiankang Liu, Mark A Supiano, James C FangAbstract:AIMS The impact of frailty on outcomes in randomized heart failure with preserved ejection fraction (HFpEF) trials has not been previously reported. This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND RESULTS Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was constructed at baseline using 39 clinical, laboratory, and self-reported variables. The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the mean FI at baseline was 0.37 ± 0.11. Four frailty classes were defined ranging from FI 0.21). Mean age was lowest for the most frail class (69 ± 9 years for Class 4; 73 ± 10 years for Class 1; P < 0.001). Body mass index, systolic blood pressure, and pulse pressure all increased as FI increased. Both primary and secondary outcomes increased as frailty severity increased. There was no interaction between frailty class and treatment effect of spironolactone. CONCLUSIONS Frailty was very common in TOPCAT HFpEF participants. Greater frailty was associated with a higher risk of cardiovascular outcomes and mortality. The benefit of spironolactone on outcomes in TOPCAT was not attenuated by frailty class.
-
atrial fibrillation in heart failure with preserved ejection fraction the topcat trial
Jacc-Heart Failure, 2018Co-Authors: Maja Cikes, Brian Claggett, Akshay S. Desai, Sanjiv J Shah, Inder S Anand, Eldrin F Lewis, Amil M Shah, Eileen Omeara, Jean L Rouleau, Nancy K SweitzerAbstract:Objectives This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p Conclusions AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302).
-
physical activity and prognosis in the topcat trial treatment of preserved cardiac function heart failure with an Aldosterone Antagonist
Circulation, 2017Co-Authors: Sheila M Hegde, Brian Claggett, Bertram Pitt, Sanjiv J Shah, Nancy K Sweitzer, Inder S Anand, Eldrin F Lewis, James C Fang, Amil M Shah, Marc A PfefferAbstract:Background:Physical activity (PA) is inversely associated with adverse cardiovascular outcomes in healthy populations, but the impact of physical activity in patients with heart failure (HF) with p...
James C Fang - One of the best experts on this subject based on the ideXlab platform.
-
spironolactone in patients with heart failure preserved ejection fraction and worsening renal function
Journal of the American College of Cardiology, 2021Co-Authors: Iris E Beldhuis, Brian Claggett, Jerome L Fleg, Eldrin F Lewis, James C Fang, Sonja M Mckinlay, Peder L Myhre, Michael R Bristow, Kevin Damman, Eileen OmearaAbstract:Abstract Background Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood. Objectives The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF. Methods In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term. Results WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p Conclusions Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF.
-
prognostic implications of plasma volume status estimates in heart failure with preserved ejection fraction insights from topcat
European Journal of Heart Failure, 2019Co-Authors: Justin L Grodin, James C Fang, Steven Philips, Wilfried Mullens, Petra Nijst, Pieter Martens, Mark H Drazner, W Wilson H Tang, Ambarish PandeyAbstract:AIMS Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF. METHODS AND RESULTS We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was -11.9% (25th-75th percentile: -17.2% to -6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS > 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all-cause death, and heart failure hospitalization, respectively (P 0.1 for all). CONCLUSION Higher calculated estimates of PVS were independently associated with a higher risk of long-term clinical outcomes in HFpEF, and particularly, heart failure hospitalization.
-
abstract 11286 spironolactone lowers loop diuretic requirements without adversely affecting renal function and electrolyte balance in patients with heart failure and preserved ejection fraction a topcat trial analysis
Circulation, 2018Co-Authors: Andreas P Kalogeropoulos, Jincy Thankachen, Javed Butler, James C FangAbstract:Introduction: In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, spironolactone (SP) reduced risk for heart failure (HF) hospitalization amo...
-
the frailty syndrome and outcomes in the topcat trial
European Journal of Heart Failure, 2018Co-Authors: Natalie A Sanders, Scott D Solomon, Brian Claggett, Akshay S. Desai, Nancy K Sweitzer, Marc A Pfeffer, Eldrin F Lewis, Jiankang Liu, Mark A Supiano, James C FangAbstract:AIMS The impact of frailty on outcomes in randomized heart failure with preserved ejection fraction (HFpEF) trials has not been previously reported. This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND RESULTS Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was constructed at baseline using 39 clinical, laboratory, and self-reported variables. The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the mean FI at baseline was 0.37 ± 0.11. Four frailty classes were defined ranging from FI 0.21). Mean age was lowest for the most frail class (69 ± 9 years for Class 4; 73 ± 10 years for Class 1; P < 0.001). Body mass index, systolic blood pressure, and pulse pressure all increased as FI increased. Both primary and secondary outcomes increased as frailty severity increased. There was no interaction between frailty class and treatment effect of spironolactone. CONCLUSIONS Frailty was very common in TOPCAT HFpEF participants. Greater frailty was associated with a higher risk of cardiovascular outcomes and mortality. The benefit of spironolactone on outcomes in TOPCAT was not attenuated by frailty class.
-
prognostic importance of temporal changes in resting heart rate in heart failure and preserved ejection fraction from the topcat study
Jacc-Heart Failure, 2017Co-Authors: Ali Vazi, Sanjiv J Shah, Jerome L Fleg, James C Fang, Marc A Pfeffe, Ia Clagge, Nancy K Sweitze, Inde S Anand, Jea L Rouleau, Sco D SolomoAbstract:Abstract Objectives The aim of this study was to examine the relationship between baseline heart rate (HR), change in HR from a preceding visit, and time-updated HR with subsequent outcomes in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. Background Higher resting HR and increase in HR over time in patients with heart failure are associated with adverse outcomes. Whether these relationships between HR and prognosis are also observed in patients with HFpEF requires further assessment. Methods In 1,767 patients enrolled in the TOPCAT trial from the Americas, the associations between baseline resting HR and change in HR from the preceding visit and clinical outcomes were examined using Cox proportional hazards models, along with the association between HR at each visit and outcome. Results Both baseline HR (adjusted hazard ratio: 1.08; 95% confidence interval: 1.04 to 1.12) and change in HR from the preceding visit (adjusted hazard ratio: 1.09; 95% confidence interval: 1.05 to 1.14; p Conclusions Baseline resting HR and change in HR over time predict outcomes in patients with HFpEF, as does time-updated HR during follow-up. These data suggest that frequent outpatient monitoring of HR, possibly with remote technologies, may identify patients with HFpEF who may be at increased risk for rehospitalization or death.
Nancy K Sweitzer - One of the best experts on this subject based on the ideXlab platform.
-
influence of age on efficacy and safety of spironolactone in heart failure
Jacc-Heart Failure, 2019Co-Authors: Orly Vardeny, Brian Claggett, Sanjiv J Shah, Inder S Anand, Eileen Omeara, Muthiah Vaduganathan, Iris E Beldhuis, Jean L Rouleau, Nancy K SweitzerAbstract:Abstract Objectives The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Background Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. Methods TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories ( Results The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p Conclusions In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302 )
-
sex differences in outcomes and responses to spironolactone in heart failure with preserved ejection fraction a secondary analysis of topcat trial
Jacc-Heart Failure, 2019Co-Authors: Miranda Merrill, Joann Lindenfeld, Nancy K Sweitzer, David P KaoAbstract:Abstract Objectives This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF). Background HFpEF affects women more frequently than men. Sex differences in responses to effects of mineralocorticoid Antagonists have not been reported. Methods This was an exploratory, post hoc, non-pre-specified analysis of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Subjects with symptomatic HF and a left ventricular ejection fraction ≥45% were randomized to spironolactone or placebo therapy. Subjects enrolled from the Americas were analyzed. The primary outcome was a composite of cardiovascular (CV) death, cardiac arrest, or HF hospitalization. Secondary outcomes included all-cause mortality, CV, and non-CV mortality and CV, HF, and non-CV hospitalization. Sex differences in outcomes and treatment effects were determined using time-to-event analysis. Results In total, 882 of 1,767 subjects (49.9%) were women. Women were older with fewer comorbidities but worse patient-reported outcomes. There were no sex differences in outcomes in the placebo arm or in response to spironolactone for the primary outcome or its components. Spironolactone therapy was associated with reduced all-cause mortality in women (hazard ratio: 0.66; p = 0.01) but not in men (pinteraction = 0.02). Conclusions In TOPCAT, women and men presented with different clinical profiles and similar clinical outcomes. The interaction between spironolactone and sex in TOPCAT overall and in the present analysis was nonsignificant for the primary outcome, but there was a reduction in all-cause mortality associated with spironolactone therapy in women, with a significant interaction between sex and treatment arm. Prospective evaluation is needed to determine whether spironolactone therapy may be effective for treatment of HFpEF in women. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)
-
the frailty syndrome and outcomes in the topcat trial
European Journal of Heart Failure, 2018Co-Authors: Natalie A Sanders, Scott D Solomon, Brian Claggett, Akshay S. Desai, Nancy K Sweitzer, Marc A Pfeffer, Eldrin F Lewis, Jiankang Liu, Mark A Supiano, James C FangAbstract:AIMS The impact of frailty on outcomes in randomized heart failure with preserved ejection fraction (HFpEF) trials has not been previously reported. This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND RESULTS Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was constructed at baseline using 39 clinical, laboratory, and self-reported variables. The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the mean FI at baseline was 0.37 ± 0.11. Four frailty classes were defined ranging from FI 0.21). Mean age was lowest for the most frail class (69 ± 9 years for Class 4; 73 ± 10 years for Class 1; P < 0.001). Body mass index, systolic blood pressure, and pulse pressure all increased as FI increased. Both primary and secondary outcomes increased as frailty severity increased. There was no interaction between frailty class and treatment effect of spironolactone. CONCLUSIONS Frailty was very common in TOPCAT HFpEF participants. Greater frailty was associated with a higher risk of cardiovascular outcomes and mortality. The benefit of spironolactone on outcomes in TOPCAT was not attenuated by frailty class.
-
atrial fibrillation in heart failure with preserved ejection fraction the topcat trial
Jacc-Heart Failure, 2018Co-Authors: Maja Cikes, Brian Claggett, Akshay S. Desai, Sanjiv J Shah, Inder S Anand, Eldrin F Lewis, Amil M Shah, Eileen Omeara, Jean L Rouleau, Nancy K SweitzerAbstract:Objectives This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p Conclusions AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302).
-
physical activity and prognosis in the topcat trial treatment of preserved cardiac function heart failure with an Aldosterone Antagonist
Circulation, 2017Co-Authors: Sheila M Hegde, Brian Claggett, Bertram Pitt, Sanjiv J Shah, Nancy K Sweitzer, Inder S Anand, Eldrin F Lewis, James C Fang, Amil M Shah, Marc A PfefferAbstract:Background:Physical activity (PA) is inversely associated with adverse cardiovascular outcomes in healthy populations, but the impact of physical activity in patients with heart failure (HF) with p...
Scott D Solomon - One of the best experts on this subject based on the ideXlab platform.
-
the frailty syndrome and outcomes in the topcat trial
European Journal of Heart Failure, 2018Co-Authors: Natalie A Sanders, Scott D Solomon, Brian Claggett, Akshay S. Desai, Nancy K Sweitzer, Marc A Pfeffer, Eldrin F Lewis, Jiankang Liu, Mark A Supiano, James C FangAbstract:AIMS The impact of frailty on outcomes in randomized heart failure with preserved ejection fraction (HFpEF) trials has not been previously reported. This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND RESULTS Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was constructed at baseline using 39 clinical, laboratory, and self-reported variables. The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the mean FI at baseline was 0.37 ± 0.11. Four frailty classes were defined ranging from FI 0.21). Mean age was lowest for the most frail class (69 ± 9 years for Class 4; 73 ± 10 years for Class 1; P < 0.001). Body mass index, systolic blood pressure, and pulse pressure all increased as FI increased. Both primary and secondary outcomes increased as frailty severity increased. There was no interaction between frailty class and treatment effect of spironolactone. CONCLUSIONS Frailty was very common in TOPCAT HFpEF participants. Greater frailty was associated with a higher risk of cardiovascular outcomes and mortality. The benefit of spironolactone on outcomes in TOPCAT was not attenuated by frailty class.
-
abstract 17827 impact of spironolactone on profibrotic markers in the treatment of preserved cardiac function heart failure with an Aldosterone Antagonist trial topcat
Circulation, 2016Co-Authors: Eileen Omeara, Scott D Solomon, Brian Claggett, Sanjiv J Shah, Inder S Anand, Simon De Denus, Michael R Zile, Martin G Sirois, Pitt Bertram, Marc A PfefferAbstract:Introduction: The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) reflects myocardial collagen turnover. Increases in collagen and Galectin-3 (Gal-3) are associated with cardiac fibrosis, a critical element in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Mineralocorticoid receptor Antagonists (MRAs) reduce myocardial fibrosis in HF with reduced EF, however their role in HFpEF remains uncertain. Hypothesis: Several biomarkers associated with myocardial fibrosis are activated in HFpEF and the MRA spironolactone modifies their levels. Methods: Biomarkers were measured at baseline (n=443) and 1-year (n=367) in serum samples obtained for TOPCAT. Changes in Gal-3, procollagen type III amino-terminal propeptide (PIIINP), procollagen type I carboxy-terminal peptide (PICP), carboxy-terminal telopeptide of collagen type I (CITP), MMPs 2 and 9, TIMP-1 and MMP-2, 9/TIMP-1 ratios were analyzed using ANCOVA models adjusted for baseline biomarker levels and relevant clinical characteristics (Table). All biomarker levels were log transformed (non-normal distributions). We also explored regional variations in the effect of spironolactone on biomarker levels. Results: Use of spironolactone was associated with reductions in MMP-2 and increases in MMP-9, while TIMP-1 remained unchanged. MMP-9/TIMP-1 ratio and Aldosterone increased significantly in all patients (Table). In North America, PICP levels were also significantly decreased (adjusted treatment effect -15%, P=0.015), but not in Russia. Gal-3, PIIINP and CITP levels were not affected by treatment in either region. Conclusions: The use of spironolactone in HFpEF is associated with significant changes in biomarkers that favor the degradation of collagen. Collagen type I (PICP, North America) appears most affected while collagen type III is unchanged (PIIINP); findings in agreement with a pressure overload model of HFpEF.
-
impact of spironolactone on longitudinal changes in health related quality of life in the treatment of preserved cardiac function heart failure with an Aldosterone Antagonist trial
Circulation-heart Failure, 2016Co-Authors: Eldrin F Lewis, Scott D Solomon, Brian Claggett, Akshay S. Desai, John F Heitner, Susan F Assmann, Haeyoung Kim, John A Spertus, Christopher T Kenwood, James C FangAbstract:Background—Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. Methods and Results—Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change...
-
prognostic importance of changes in cardiac structure and function in heart failure with preserved ejection fraction and the impact of spironolactone
Circulation-heart Failure, 2015Co-Authors: Amil M Shah, Brian Claggett, Bertram Pitt, Sanjiv J Shah, Nancy K Sweitzer, Inder S Anand, Jerome L Fleg, Marc A Pfeffer, Anita Deswal, Scott D SolomonAbstract:Background—Limited data exist regarding the impact of Aldosterone Antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction. Methods and Results—Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The impact of spironolactone therapy on measures of cardiac structure and function was assessed in the study population overall, and change in echocardiographic measures was associated with the subsequent occurrence of the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Spironola...
-
prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone
Circulation, 2015Co-Authors: Amil M Shah, Brian Claggett, Bertram Pitt, Sanjiv J Shah, Nancy K Sweitzer, Inder S Anand, Marc A Pfeffer, Li Liu, Scott D SolomonAbstract:Background—Impairment in left ventricular systolic function has been described in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether left ventricular longitudinal strain (LS) is predictive of cardiovascular outcomes in HFpEF beyond clinical and conventional echocardiographic measures. Methods and Results—LS was assessed by 2-dimensional speckle-tracking echocardiography at baseline in 447 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 years (interquartile range, 1.5–3.9 years), 115 patients experienced the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS <15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted hazard ratio, 2.14; 95% confidence interval, 1.26–3.66; P=0.005), cardiovascular dea...
Sanjiv J Shah - One of the best experts on this subject based on the ideXlab platform.
-
influence of age on efficacy and safety of spironolactone in heart failure
Jacc-Heart Failure, 2019Co-Authors: Orly Vardeny, Brian Claggett, Sanjiv J Shah, Inder S Anand, Eileen Omeara, Muthiah Vaduganathan, Iris E Beldhuis, Jean L Rouleau, Nancy K SweitzerAbstract:Abstract Objectives The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Background Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. Methods TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories ( Results The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p Conclusions In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302 )
-
atrial fibrillation in heart failure with preserved ejection fraction the topcat trial
Jacc-Heart Failure, 2018Co-Authors: Maja Cikes, Brian Claggett, Akshay S. Desai, Sanjiv J Shah, Inder S Anand, Eldrin F Lewis, Amil M Shah, Eileen Omeara, Jean L Rouleau, Nancy K SweitzerAbstract:Objectives This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p Conclusions AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302).
-
incident hyperkalemia hypokalemia and clinical outcomes during spironolactone treatment of heart failure with preserved ejection fraction analysis of the topcat trial
Journal of Cardiac Failure, 2018Co-Authors: Akshay S. Desai, Sanjiv J Shah, Jerome L Fleg, Sonja M Mckinlay, Jiankang Liu, Marc A Pfeffe, Ia Clagge, Eldri F Lewis, Eilee Omeara, Nancy K SweitzeAbstract:Abstract Background In patients with heart failure and preserved ejection fraction (HF-PEF) randomized in the Americas as part of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, treatment with spironolactone enhanced the risk of hyperkalemia but reduced the risk of hypokalemia. We examined the clinical correlates and prognostic implications of incident hypo- and hyperkalemia during study follow-up. Methods We defined the region-specific incidence of hypokalemia (potassium [K+] Results In the Americas, assignment to spironolactone increased risk for hyperkalemia (hazard ratio 3.21, 95% confidence interval 2.46–4.20, P Conclusions Both hyperkalemia and hypokalemia are associated with heightened risk for mortality in HF-PEF. Use of spironolactone in this population requires careful laboratory surveillance of K+ and creatinine, particularly in high-risk groups.
-
prognostic importance of temporal changes in resting heart rate in heart failure and preserved ejection fraction from the topcat study
Jacc-Heart Failure, 2017Co-Authors: Ali Vazi, Sanjiv J Shah, Jerome L Fleg, James C Fang, Marc A Pfeffe, Ia Clagge, Nancy K Sweitze, Inde S Anand, Jea L Rouleau, Sco D SolomoAbstract:Abstract Objectives The aim of this study was to examine the relationship between baseline heart rate (HR), change in HR from a preceding visit, and time-updated HR with subsequent outcomes in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. Background Higher resting HR and increase in HR over time in patients with heart failure are associated with adverse outcomes. Whether these relationships between HR and prognosis are also observed in patients with HFpEF requires further assessment. Methods In 1,767 patients enrolled in the TOPCAT trial from the Americas, the associations between baseline resting HR and change in HR from the preceding visit and clinical outcomes were examined using Cox proportional hazards models, along with the association between HR at each visit and outcome. Results Both baseline HR (adjusted hazard ratio: 1.08; 95% confidence interval: 1.04 to 1.12) and change in HR from the preceding visit (adjusted hazard ratio: 1.09; 95% confidence interval: 1.05 to 1.14; p Conclusions Baseline resting HR and change in HR over time predict outcomes in patients with HFpEF, as does time-updated HR during follow-up. These data suggest that frequent outpatient monitoring of HR, possibly with remote technologies, may identify patients with HFpEF who may be at increased risk for rehospitalization or death.
-
physical activity and prognosis in the topcat trial treatment of preserved cardiac function heart failure with an Aldosterone Antagonist
Circulation, 2017Co-Authors: Sheila M Hegde, Brian Claggett, Bertram Pitt, Sanjiv J Shah, Nancy K Sweitzer, Inder S Anand, Eldrin F Lewis, James C Fang, Amil M Shah, Marc A PfefferAbstract:Background:Physical activity (PA) is inversely associated with adverse cardiovascular outcomes in healthy populations, but the impact of physical activity in patients with heart failure (HF) with p...