PIONEER HF: Sacubitril/valsartan in African-American Patients with ADHF

11 Nov, 20

Introduction

The incidence of heart failure (HF) is highest among African patients. As compared to other racial and ethnic groups, African patients respond differently to treatment with angiotensin-converting enzyme inhibitors. Little is known about the response of African patients with acute decompensated heart failure (ADHF) to sacubitril/valsartan, (an angiotensin receptor–neprilysin inhibitor).

Aim

To compare the efficacy and safety of sacubitril/valsartan vs. enalapril in African-Americans and non-African-Americans with ADHF

Patient Profile

Patients (age ≥18 years; n=881) with reduced ejection fraction (EF) (left ventricular EF [LVEF] ≤40% and an N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥1600 pg/ml or a B-type natriuretic peptide (BNP) ≥ 400 pg/ml.
All patients had a primary diagnosis of ADHF, including signs and symptoms of fluid overload.
The enrollment period for patients ranged from no less than 24 hours up to 10 days after initial presentation to the hospital (median; 68 hours), while they were still hospitalized.
Patients were hemodynamically stable (defined as; maintenance of a systolic blood pressure of ≥100 mm Hg for the preceding 6 hours, with no increase in the dose of intravenous [IV] diuretics and no use of IV vasodilators during the preceding 6 hours and no use of IV inotropes during the preceding 24 hours) before randomization.

Methods

Study Design

A sub-group analysis of PIONEER-HF (Comparison of Sacubitril/Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute HF Episode) trial
PIONEER-HF was a multi-centre, double-blind, randomized, active-controlled clinical trial

Treatment Strategy

A washout period of 36 hours was ensured before initiating the sacubitril/valsartan treatment.
Patients were randomized as follows:

All the patients were monitored for a minimum of 6 hours after the administration of the third dose before discharge from the hospital.

Follow-up Visits

Week 1, 2 and every 2 weeks thereafter

Outcomes

Primary Efficacy Outcome

The time-averaged proportional change in the NT proBNP from baseline through weeks 4 and 8, according to race

Primary Safety Outcome

Worsening renal function (an increase in the serum creatinine concentration of ≥0.5 mg/dL and a decrease in the estimated glomerular filtration rate [eGFR] ≥25%)
Hyperkalemia (a serum potassium concentration of ≥5.5 mmol/L)
Symptomatic hypotension
Angioedema

Secondary Efficacy Outcome

The time-averaged proportional changes in the high-sensitivity troponin T (Hs-TnT) concentration

Results

Of the entire study population, 36% (n=316) were African-Americans, 58% (n=515) were White and 5.7% (n=50) were of other racial groups.
Treatment with sacubitril/valsartan was associated with a greater reduction in NT-proBNP concentration at weeks 4 and 8 as compared with enalapril in both African-Americans and non-African-American patients (Table 1).
Similarly, sacubitril/valsartan rather than enalapril treatment was associated with a greater reduction in Hs-TnT concentration irrespective of race (Table 1)

Table 1: Changes in biomarkers in the study groups as per the race

Biomarker	African-Americans		Non-African-Americans
Biomarker	Ratio for S/V Versus Enalapril (95% CI)	p Value	Ratio for S/V Versus Enalapril (95% CI)	p Value
NT-proBNP	0.71 (0.58–0.88)	0.002	0.71 (0.61–0.83)	<0.001
Hs-TNT	0.87 (0.74–1.03)	0.10	0.84 (0.74–0.95)	0.004

Compared with enalapril, sacubitril/valsartan treatment was also associated with 53% and 35% risk reduction for the pre-specified exploratory composite of cardiovascular death or HF rehospitalization in African-American and non-African-American patients, respectively (Fig 1)

Fig 1: Clinical outcomes in the study groups as per race

Race had no impact on any of the safety outcomes considered during this study.

Conclusions

Amongst African-American patients hospitalized for ADHF, the in-hospital initiation of sacubitril/valsartan was superior to enalapril in terms of reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization.
Initiation of sacubitril/valsartan was equally safe and effective in African-American and non-African-American patients with ADHF following hemodynamic stabilization.

J Am Coll Cardiol HF 2020;8:859–66.