Angiotensin Receptor Neprilysin Inhibition Compared With Individualized Medical Therapy for Comorbidities in Patients With Heart Failure and Preserved Ejection Fraction - PARALLAX
Contribution To Literature:
The PARALLAX trial showed that sacubitril/valsartan was associated with a reduction in NT-proBNP; however, it did not improve 6-minute walk distance.
The goal of the trial was to evaluate angiotensin receptor neprilysin inhibition (sacubitril/valsartan) compared with individualized medical therapy among patients with preserved or mid-range ejection fraction.
Eligible patients were randomized to sacubitril/valsartan (n = 1,286) versus individualized medical therapy (n = 1,286). Patients were assigned to one of three strata: 1) sacubitril/valsartan 93/103 mg twice daily versus enalapril 10 mg twice daily, 2) sacubitril/valsartan 93/103 mg twice daily versus valsartan 160 mg twice daily, or 3) sacubitril/valsartan 93/103 mg twice daily versus placebo.
- Total number of enrollees: 2,572
- Duration of follow-up: 24 weeks
- Mean patient age: 73 years
- Percentage female: 50%
- Percentage with diabetes: 39%
- ≥45 years of age
- Left ventricular ejection fraction (LVEF) >40%
- New York Heart Association (NYHA) class II-IV requiring diuretics
- Left atrial enlargement and/or LV hypertrophy
- Patients treated with angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker for hypertension
- Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) <75
- N-terminal pro-B-type natriuretic peptide (NT-proBNP) >220 pg/ml if not in atrial fibrillation or >600 pg/ml if atrial fibrillation
- Acute decompensated heart failure
- Walk distance limited by noncardiac comorbidity
- Alternative diagnosis for symptoms such as chronic obstructive pulmonary disease
- Systolic blood pressure <110 mm Hg or ≥180 mm Hg
The primary co-outcome, NT-proBNP change from baseline to week 12, favored sacubitril/valsartan vs. individualized medical therapy (adjusted geometric mean ratio 0.84, p < 0.0001).
The primary co-outcome, 6-minute walk distance change from baseline to week 24, was similar between sacubitril/valsartan vs. individualized medical therapy (adjusted mean difference -2.5, p = 0.24).
- NYHA class change from baseline to week 24 was similar between sacubitril/valsartan vs. individualized medical therapy (odds ratio 1.01, p = 0.93).
- KCCQ-CSS change from baseline to week 24 was similar between sacubitril/valsartan vs. individualized medical therapy (least square mean of difference 0.52, p = 0.48).
- Patients with ≥1 serious adverse event: 14.5% with sacubitril/valsartan vs. 14.9% with individualized medical therapy.
- Change in eGFR: -1.47 ml/min/1.73 m2 with sacubitril/valsartan vs. -2.57 ml/min/1.73 m2 with individualized medical therapy (p = 0.016).
- Death due to cardiac failure or heart failure hospitalization: (hazard 0.64, p = 0.034, favoring sacubitril/valsartan vs. individualized medical therapy).
Among patients with heart failure due to preserved or mid-range ejection fraction, angiotensin receptor neprilysin inhibition compared with individualized medical therapy was associated with a reduction in NT-proBNP. However, angiotensin receptor neprilysin inhibition was not associated with improvements in 6-minute walk distance, KCCQ-CSS, or NYHA class. Sacubitril/valsartan compared with individualized medical therapy was associated with a reduction in death or heart failure hospitalization and slowed decline in renal function. Overall, with these mixed results, sacubitril/valsartan deserves further study in this patient population.
Presented by Dr. Burkert Pieske at the European Society of Cardiology Virtual Congress, August 30, 2020.
Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension
Keywords: ESC Congress, ESC20, Atrial Fibrillation, Diuretics, Geriatrics, Glomerular Filtration Rate, Heart Failure, Hypertension, Hypertrophy, Left Ventricular, Natriuretic Peptide, Brain, Natriuretic Peptides, Renal Insufficiency, Secondary Prevention, Stroke Volume
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