Abstract 16477: Sacubitril/valsartan as a Treatment for Resistant Hypertension in Patients With Heart Failure and Preserved Ejection Fraction

Abstract

Objective: Heart failure with preserved ejection fraction (HFpEF) is typically a hypertensive phenotype and many HFpEF patients have difficult to control hypertension. We examined the effect of neprilysin inhibition on resistant hypertension in HFpEF patients in the PARAGON-HF trial. Patients entered a 1 to 4-week valsartan run-in (target dose 80mg bd), followed by sacubitril/valsartan run-in, before randomization to valsartan or sacubitril/valsartan (target doses 160mg bd or 200mg bd respectively). Design and methods: Patients were examined according to different definitions of resistant hypertension using systolic blood pressure (SBP) at the end of valsartan run-in. Group 1: SBP≥140mmHg (≥135mmHg if diabetes) despite treatment with a calcium channel blocker (CCB), diuretic and valsartan, Group 2: SBP≥130mmHg despite treatment with a CCB, diuretic and valsartan, or SBP<130mmHg despite treatment with a CCB, diuretic, mineralocorticoid receptor antagonist (MRA) and valsartan, and Group 3: SBP≥140mmHg (≥135mmHg if diabetes) despite treatment with a CCB, diuretic, MRA and valsartan (≥4 classes of SBP-reducing therapy, including MRA). We examined reduction in SBP from end of valsartan run-in to weeks 4 and 16 after randomization and the proportion of patients with controlled SBP at week 16 on sacubitril/valsartan vs valsartan. Results: Of 4796 patients randomized, criteria for resistant hypertension were fulfilled in 726 (15%) using the Group 1 definition, 1146 (24%) using the Group 2 definition and 132 (3%) in the third group. The combination of neprilysin inhibitor, angiotensin receptor blocker, CCB and diuretic (+/-MRA) reduced SBP and significantly increased the proportion of patients with controlled SBP (Table). Conclusion: Sacubitril/valsartan may be useful in treating resistant hypertension in patients with HFpEF, even in those who continue to have an elevated SBP despite treatment with at least 4 antihypertensive drug classes, including an MRA.