Publications by authors named "Martin P Lefkowitz"
Background: Lower estimated glomerular filtration rate (eGFR) may be one of the major reasons for hesitation or failure to initiate potentially beneficial therapies in patients with heart failure (HF).
Objectives: This study sought to assess if the effects of sacubitril/valsartan (vs valsartan) on cardiovascular outcomes differ according to baseline kidney function in patients with HF with preserved ejection fraction.
Methods: The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial was global clinical trial of 4,796 patients with chronic HF and left ventricular ejection fraction (LVEF) ≥45% randomly assigned to sacubitril/valsartan or valsartan.
Background: Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood.
Methods: We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks.
Article Synopsis
- The study investigated the impact of hypotension on heart failure outcomes using data from the PARADIGM-HF trial, focusing on the differences between asymptomatic and symptomatic hypotension.
- Out of 8,399 patients, 16% had only asymptomatic hypotension, while 11.1% experienced symptomatic hypotension, with those having symptomatic hypotension being older and having more cardiovascular issues.
- Despite the risks associated with either type of hypotension, the heart failure medication sacubitril/valsartan showed consistent effectiveness and safety compared to enalapril across all patient groups.
Background: Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S.
View Article and Find Full Text PDFArticle Synopsis
- - The study investigated whether the heart failure medication sacubitril/valsartan could lead to cognitive impairment, as it affects enzymes that degrade amyloid-β peptides, which are linked to Alzheimer's disease.
- - Researchers used the Mini-Mental State Examination (MMSE) to assess cognitive function changes over 96 weeks in a subset of heart failure patients from the PARAGON-HF trial, comparing those on sacubitril/valsartan to those on valsartan alone.
- - Results showed no significant difference in cognitive decline between the two groups, with both medications resulting in nearly identical changes in MMSE scores, suggesting sacubitril/valsartan does not have a negative effect on cognitive function in these patients. *
Background: The Kidney Disease Improving Global Outcomes (KDIGO) classification integrates both estimated glomerular filtration rate and urine-albumin-creatinine ratio to stratify risk more comprehensively in patients with chronic kidney disease. There are limited data assessing whether this classification system is associated with prognosis and treatment response in heart failure populations.
Objectives: The aim of this study was to evaluate the relative treatment effects of sacubitril/valsartan across the KDIGO risk categories in patients with HFrEF.
Aim: Blood urea nitrogen (BUN) to creatinine ratio is associated with worse outcomes in acute heart failure (HF) but little is known about its importance in chronic HF.
Methods And Results: We combined individual patient data from clinical trials (HF with reduced ejection fraction [HFrEF]: PARADIGM-HF, ATMOSPHERE and DAPA-HF, and HF with preserved ejection fraction [HFpEF]: PARAGON-HF and I-PRESERVE). The primary outcome examined was a composite time to first HF hospitalization or cardiovascular death; its components and all-cause death were also examined.
Article Synopsis
- * In the PARAGON-HF study, patients with left ventricular ejection fraction of ≥45% were analyzed, showing that higher RDW levels were linked to worse clinical outcomes, including increased hospitalizations and cardiovascular deaths.
- * The study found that sacubitril/valsartan reduced RDW more effectively than valsartan over 48 weeks, adding valuable prognostic information to existing predictors without changing the effects based on initial RDW levels.
Background: Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia.
Objectives: The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure).
Aims: It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure.
Methods And Results: Aldosterone, cystatin C, high-sensitivity troponin T (hs-TnT), galectin-3, growth differentiation factor-15 (GDF-15), kidney injury molecule-1, matrix metalloproteinase-2 and -9, soluble suppression of tumourigenicity-2, tissue inhibitor of metalloproteinase-1 (TIMP-1) and urinary albumin to creatinine ratio were measured in 1559 of PARADIGM-HF participants. We tested whether these biomarkers, individually or collectively, improved the performance of the PREDICT-HF prognostic model, which includes clinical, routine laboratory, and natriuretic peptide data, for the primary endpoint and cardiovascular and all-cause mortality.
Aims: The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) compared to the creatinine-only equation.
Methods And Results: CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creatinine) equation in a subpopulation of Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF). Patients were categorized according to difference in eGFR using the two equations: Group 1 (<-10 mL/min/1.
Background: The ratio of ucGMP (urinary cyclic guanosine monophosphate) to BNP (B-type natriuretic peptide) is thought to reflect the responsiveness of tissues to natriuretic peptides.
Methods: We examined the relationship between ucGMP/BNP ratio and clinical outcomes, the effect of sacubitril/valsartan, compared with enalapril, on the ucGMP/BNP ratio, and the efficacy of sacubitril/valsartan on clinical outcomes according to baseline ucGMP/BNP ratio in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). ucGMP/BNP ratio was available at baseline (N=2031), 1 month (N=1959), and 8 months after randomization (N=1746).
Aim: PARADISE-MI examined the efficacy of sacubitril/valsartan in acute myocardial infarction (AMI) complicated by reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both. We sought to assess the trajectory of pulmonary congestion using lung ultrasound (LUS) and its association with cardiac structure and function in a pre-specified substudy.
Methods And Results: Patients without prior heart failure (HF) underwent eight-zone LUS and echocardiography at baseline (±2 days of randomization) and after 8 months.
Aims: Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).
Methods And Results: Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified.
Aims: Heart failure (HF) is associated with poor health-related quality of life (HRQL). Patients with HF with preserved ejection fraction (HFpEF) have similar HRQL impairment as those with reduced ejection fraction. This study describes the impact of sacubitril/valsartan on HRQL in patients with HFpEF enrolled in the PARAGON-HF trial.
View Article and Find Full Text PDFBackground: Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients.
Objectives: This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.
Methods: Frailty was measured by using the Rockwood cumulative deficit approach.
Effects of sacubitril/valsartan versus valsartan on renal function in patients with and without diabetes and heart failure with preserved ejection fraction: insights from PARAGON-HF.
Eur J Heart Fail
May 2022
Aims: Diabetes is associated with a faster rate of renal function decline in patients with heart failure (HF). Sacubitril/valsartan attenuates the deterioration of renal function to a greater extent in patients with diabetes and HF with reduced ejection fraction compared with renin-angiotensin system inhibitors alone. We assessed whether the same may be true in HF with preserved ejection fraction (HFpEF).
View Article and Find Full Text PDFAims: Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin-neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF.
Methods And Results: We combined data from PARADIGM-HF (EF ≤40%; n = 8399) and PARAGON-HF (EF ≥45%; n = 4796) in a pre-specified pooled analysis.
Aims: Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias.
View Article and Find Full Text PDFAim: There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.
Methods And Results: Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible.
Background Little is known about the impact of chronic obstructive pulmonary disease (COPD) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We examined outcomes in patients with heart failure with preserved ejection fraction, according to COPD status, in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and cardiovascular death.
View Article and Find Full Text PDFAims: Sacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline-directed medical therapy for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β-blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial.
View Article and Find Full Text PDFBackground Dyslipidemia is common in heart failure with preserved ejection fraction. Sacubitril/valsartan improves glycemic control and augments natriuretic peptide signaling, providing mechanisms by which sacubitril/valsartan may affect serum lipids. However, empiric data on these effects are lacking.
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