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Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD

Phase 4
Withdrawn
Conditions
Congestive Heart Failure
Hypertension
Interventions
Registration Number
NCT03279861
Lead Sponsor
University of Maryland, Baltimore
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
EntrestoEntrestoFirst-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily
Usual medsEntrestoFirst-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily
Usual medsValsartanFirst-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily
EntrestoValsartanFirst-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily
Primary Outcome Measures
NameTimeMethod
Time spent with MAP < 85 mmHg2 months

Daily mean arterial pressure (MAP) \< 85 mmHg

Secondary Outcome Measures
NameTimeMethod
Number of drugs2 months

Number of anti-hypertensive drugs needed to achieve MAP \< 85 mmHg

Pump flow2 months

Correlation of pump flow with daily MAP

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