Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD

University of Maryland Baltimore (UMB)

Status and phase: Withdrawn; Phase 4

Conditions: Hypertension; Congestive Heart Failure

Treatments: Drug: Entresto; Drug: Valsartan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03279861

HP-00076889

Details and patient eligibility

About

This pilot, feasibility study evaluates the efficacy of sacubitril-valsartan (Entresto) versus usual anti-hypertensive medications in patients with left ventricular assist devices (LVAD). It also measures diurnal blood pressure variations in the context of continuous flow physiology.

Full description

Left ventricular assist devices (LVAD) have become a life-saving therapy for patients with ACC/AHA stage D congestive heart failure (CHF). Despite longevity and improved quality of life, LVAD-supported patients are plagued with adverse events, the most debilitating of all is stroke. Ischemic and hemorrhagic strokes have been associated with hypertension (mean arterial pressure, or MAP > 90 mmHg) in addition to out-of-range INR and aspirin doses. Strict blood pressure control has been shown in a recent randomized trial to confer a significant decline in stroke rates of patients implanted with the Heartware LVAD. Patients with poorly controlled hypertension are also at risk for inadequate left-ventricular unloading and worsening CHF due to the exquisite sensitivity to afterload of the continuous flow LVAD.

There are no guidelines for the use of anti-hypertensives in LVAD patients. Most are started on standard CHF therapies, though this practice varies greatly across LVAD centers. The angiotensin receptor blocker-neprilysin inhibitor sacubitril-valsartan (Entresto) is a potent anti-hypertensive mediation that was recently approved by the Food and Drug Administration for the treatment of patients with heart failure and low ejection fraction. We aim to randomly assign patients to receive Entresto or usual anti-hypertensive therapy for blood pressure control, then crossover to the other arm after 30 days. Daily blood pressure measurements will be performed and correlated with LVAD pump flows and waveform analysis.

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• More than 30 days after LVAD implant
• Ambulatory
• MAP > 85 mmHg requiring initiation of anti-hypertensive medications

Exclusion criteria

• Allergy to ACEI or ARB
• eGFR < 30 mL/min/1.73m2
• K > 5.4 mmol/L
• MAP < 60
• Inability to check blood pressure at home
• Lack of prescription coverage
• Frequent hospitalizations (monthly)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Entresto

Active Comparator group

Description:

First-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily

Treatment:

Drug: Valsartan

Drug: Entresto

Usual meds

Active Comparator group

Description:

First-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily

Treatment:

Drug: Valsartan

Drug: Entresto