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Careful volume assessment appears to be the critical factor in achieving clinical trial dose of sacubitril/valsartan in the community.

Session Poster Session 2

Speaker Maria Ferre-Vallverdu

Event : Heart Failure 2019

  • Topic : heart failure
  • Sub-topic : Pharmacotherapy
  • Session type : Poster Session

Authors : M Ferre-Vallverdu (Dublin,IE), RB Pharithi (Dublin,IE), E O'connell (Dublin,IE), M Walshe (Dublin,IE), J Barton (Dublin,IE), D O'hare (Dublin,IE), M Ledwidge (Dublin,IE), J Gallagher (Dublin,IE), K Mcdonald (Dublin,IE)

M Ferre-Vallverdu1 , RB Pharithi1 , E O'connell1 , M Walshe1 , J Barton1 , D O'hare1 , M Ledwidge1 , J Gallagher1 , K Mcdonald1 , 1St Vincent's University Hospital, Heart Failure Unit - Dublin - Ireland ,

Chronic Heart Failure: Pharmacotherapy

Introduction: In the PARADIGM-HF trial, sacubitril/valsartan (S/V) has been shown to improve morbidity and life expectancy in HF-REF patients. Real world data, while limited, indicate a similar clinical response. However, achievement of clinical trial dose (CTD; 97/103 mg BD) of S/V appears to be a challenge with only one data set to date reporting CTD in >50% of their cohort. Early data indicate that CTD may be more effective in improving important metrics such as LVEF. Therefore, identifying methods of facilitating achievement of CTD would be of importance. 

Methods: 322 HF-REF patients were switched from ACEi/ARB to S/V between May 2016 and August 2018. Patients still on the titration process (n=25) were excluded. Baseline and follow-up clinical characteristics were collected. Univariate and multivariate test were used to analyze predictors of achieving CTD.

Results: 12.4% patients have not tolerated S/V as a result of symptomatic hypotension (52.4%), impairment of renal function (23.6%), gastrointestinal symptoms (13.5%) and hyperkalaemia (10.5%). Of the 257 patients successfully started on this agent, CTD has been achieved in 75.5% patients, 11.4% patients have been maintained on 49/51mg BD and 8.1% patients on 24/26mg BD. Symptomatic hypotension (73.6%) has been the main impediment to achieve CTD, followed by renal deterioration (12.2%) and then hyperkalaemia and gastro-intestinal symptoms (5.3% each). Multivariate analysis of variables related to achieving CTD showed that down-titration of loop diuretic was the most important predictor (Table 1). Reduction in diuretic has been required in 37.2% of patients with a mean reduction in diuretic need of 10mg furosemide equivalent/patient.

In conclusion, achievement of CTD with S/V is achievable in the majority of community population. Hypotension being the major barrier to achieving maximum dose and the need to down titrate diuretic in a large percentage of the population strongly underline the need to pay close clinical attention to volume status during the titration process.



OR (95%CI)

p value


p value


0.99 (0.97-1.01)


1.02 (0.99-1.05)



1.04 (0.61-1.78)


0.78 (0.4-1.54)


Diuretic dose decrease

1.77 (1.05-2.97)


2.05 (1.14-3.68)


Baseline log-NTproBNP

0.81 (0.66-1.01)


0.82 (0.64-1.05)


Baseline eGFR

1.02 (1.01-1.03)


1.02 (1-1.04)


Baseline haemoglobin

1.21 (1.04-1.4)


1.15 (0.96-1.38)


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