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.
- Angiotensin Receptor-Neprilysin Inhibitor