Background: Based on the PARADIGM-HF study trial, sacubitril/valsartan (SV) was
approved by NICE in April 2016 (TA388) for patients with symptomatic heart
failure. SV is recommended in patients with a left ventricular ejection
fraction (LVEF) ≤35% despite a stable dose of ACE inhibitor (ACEi) or
angiotensin receptor blocker (ARB), and large numbers are potentially eligible
for this first-in-class drug. However, there is a lack of real world experience
of both drug tolerability and systems for initiation and monitoring in
overstretched heart failure services.
Methods: Suitable patients were identified and started on SV by heart failure
specialists. Dedicated, registrar-delivered monitoring and up titration clinics
were established. Patients were reviewed 2-4 weekly. Symptoms, vital signs,
biochemistry and hospital admissions were recorded at each visit. Once stable
on optimal doses, patients were discharged to primary care, as pre-arranged
with the District Prescribing Committee. Our initial 6-month experience has
been analysed.
Results: 69 patients (mean age 63.2±11.6 years) were commenced on SV. Mean LVEF
27.5±6.7%; mean baseline eGFR 66.1±21.9 ml/min/1.73m2. Prior to
initiation of SV, mean baseline ACEi/ARB dose was equivalent to 16.3±6.7 mg
enalapril daily. Overall 68/69 (98.6%) prescriptions of SV were NICE TA388
compliant (1 patient ACEi/ARB intolerant).
9 patients (13.0%)
stopped the medication due to adverse effects (PARADIGM-HF 17.8%), whilst
another 3 patients (4.3%) were down titrated to a tolerable lower dose. 15.9%
of all patients experienced symptomatic hypotension (PARADIGM-HF 14.0%). No
episodes of angioedema, nor significant deterioration in renal function (≥50%
reduction in eGFR) were observed. Only 1 (1.4%) patient was hospitalised with
decompensated heart failure symptoms, but 3 (4.3%) patients were admitted with
syncope secondary to orthostatic hypotension.
A total of 36
patients were discharged, with a median follow up time of 39 days (IQR 23) from
commencement to stable discharge dose – each requiring 1 initiation
consultation and a mean of 2.4±1.0 follow up consultations. The majority of
patients 25 (69.4%) were discharged at the highest dose - 97/103 mg BD. 23 (63.9%)
of those discharged reported a subjective improvement in symptoms and quality
of life.
Conclusions: Initiation of SV and dose optimisation in clinical practice represents
a significant burden of additional work for heart failure teams. Dedicated,
registrar-led outpatient clinics to monitor patients commenced on SV by heart
failure specialists can successfully address this.
Prescribing within NICE TA388 guidelines in real world
patients, there were similar drug tolerance and adverse event rates to those
reported in PARADIGM-HF. However, the lower mean age within this particular
population, who were carefully selected, may indicate that such findings are
not representative of the entire heart failure population.
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