Translation of clinical trial to real world practice: can sacubitril-valsartan be safely titrated to target dose, 97/103mg bi-daily, in clinical practice and what baseline characteristics predict successful titration?

Abstract

Background: Sacubitril-valsartan significantly improved clinical outcomes. Unfortunately real world data is lacking. We aimed to determine the feasibility of titrating sacubitril-valsartan to target dose and identify predictors of success.Methods: We performed a retrospective analysis of 235 consecutive patients prescribed sacubitril-valsartan between 08/2016 and 01/2018. Baseline characteristics and dose titration were compared to Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Logistic regression multivariable model was utilised to identify independent factors associated with successful titration.Results: At six months 235 patients (24% female) were titrated on sacubitril-valsartan, 120 patients (51%) reached target dose whilst 26 patients (11%) discontinued, primarily due to hypotension. Compared to PARADIGM-HF our patients were younger with lower baseline blood pressure and less ischaemic cardiomyopathy (all P-value <0.05). Several baseline characteristics predicted successful titration [Table 1].Conclusion: Sacubitril-valsartan can be titrated safely in clinical practice and achieve results comparable to PARADIGM-HF. Several baseline characteristics involving patient factors, markers of disease severity and systems of care are associated with successful titration to target dose.