ARNI reduces NT-proBNP, but does not improve functional capacity in HFpEF
Angiotensin receptor neprilysin inhibition compared with individualized medical therapy for comorbidities in patients with heart failure and preserved ejection fraction – the PARALLAX trial
Presented at ESC Congress 2020 by Burkert Pieske (Berlin, Germany)
Introduction and methods
Half of patients with heart failure have heart failure with preserved ejection fraction (HFpEF) or mid-range ejection fraction (HFmrEF). HFpEF and HFmrEF are associated with increased risk of morbidity and mortality. Guidelines recommend diuretics for symptom control and individualized management of comorbidities in these patients. There are no specific therapies that improves outcomes in this patient population. Results from the PARAGON-HF trial have suggested that may be benefit with sacubitril/valsartan (S/V) in patients with HFpEF.
The PARALLAX trial evaluated the effect of S/V on a marker of disease severity and prognosis, NT-proBNP, and the effect on exercise capacity (6MWT) when compared to individual medical therapy (IMT) in patients with HFpEF. In addition, the effect of S/V on quality of life (QoL), comorbidities and tolerability and safety were examined.
This was a prospective 24-week, randomized, active-controlled, parallel-group trial, that enrolled patients with NYHA class II-IV, LVEF >40%, evidence of LVH or LAE by echocardiography, elevated NT-proBNP and on optimized treatment of comorbidities. 2572 Patients were randomized to S/V or IMT in a 1:1 ratio. There were 3 strata: patients already on ACEi were randomized to S/V or enalapril, patients already on ARB were randomized to S/V or valsartan, and patients not on any RAAS inhibition were randomized to S/V or placebo. Mean baseline LVEF was 57% (SD 8.3) in the S/V group and 56% (8.0) in the IMT group.
- Change in NT-proBNP was greater in the S/V group compared to the IMT group (adjusted geometric mean ratio at week 12 [S/V vs. IMT]: 0.84 [0.80-0.88], P<0.0001).
- Change in 6MWD from baseline to week 24 was not different between the two groups (adjusted mean difference [S/V vs IMT]: -2.50 [-8.53 to 3.53] m, P=0.42).
- Change in KCCQ-CSS from baseline to week 24 was not different between the S/V group and the IMT group (LSM of difference [S/V vs. IMT] 0.52 [-0.93 to 1.97, P=0.48).
- Proportion of patients that improved NYHA class from baseline to week 24 was not different between the two treatment arms.
- Analysis of cardiac failure events leading to hospitalization and/or death documented as adverse events showed that first hospitalization due to HF was reduced in the S/V group compared to IMT (HR 0.49, 95%CI: 0.30-0.81, P=0.005) and also composite of time to death due to cardiac failure or HF hospitalization was reduced with S/V treatment compared to IMT (HR 0.64, 95%CI: 0.42-0.97, P=0.034).
Treatment with S/V in the PARALLAX trial showed a reduction in NT-proBNP at 12 weeks compared to IMT, but no improvement after 24 weeks with S/V was observed on 6MWD, NYHA class or QoL when compared to IMT.
- Our reporting is based on the information provided at the ESC congress -