Angiotensin Receptor Neprilysin Inhibition Compared With Individualized Medical Therapy for Comorbidities in Patients With Heart Failure and Preserved Ejection Fraction - PARALLAX

Aug 30, 2020
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC, MBA
Date Presented:
08/30/2020
Date Updated:
08/30/2020
Original Posted Date:
08/30/2020
References

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.

Description:

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.


Study Design

  • Randomized
  • Parallel
  • Double-blind
  • Stratification

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%

Inclusion criteria:

  • ≥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

Exclusion criteria:

  • 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

Principal Findings:

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).

Secondary outcomes:

  • 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).

Interpretation:

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.

References:

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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