Publications by authors named "M 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.
Aims: Beta-blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho-inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta-blocker compared to those treated with a beta-blocker.
Methods And Results: We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta-blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM-HF.
Article Synopsis
- Heart failure events in cardiovascular trials are often evaluated through centralized review, but its impact on treatment effect accuracy (in terms of hazard ratios) is uncertain.
- In a study of seven trials, positive adjudication rates for heart failure events were generally lower than for cardiovascular deaths, affecting subsequent mortality risk.
- Overall, while central adjudication showed some correlation between event types, it didn’t significantly change the results, suggesting that the need for centralized review should be tailored to each trial's objectives.
Aims: Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit-to-visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well-characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF).
Methods And Results: PARADIGM-HF and PARAGON-HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF).
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.