Although sacubitril/valsartan was associated with significant reductions in N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure with preserved ejection fraction (HFpEF) compared with individual RAAS blockade at 12 weeks, no significant difference in 6-minute walk distance or secondary endpoints were found in the phase 3 PARALLAX study [1].
Previously, the PARAGON-HF trial showed that sacubitril/valsartan improves morbidity and mortality outcomes of patients with HFpEF [2]. The PARALLAX study aimed to build on these previous clinical data by assessing the effects of sacubitril/valsartan in heart failure patients (n=2,572) with an ejection fraction >40%, evidence of left ventricular hypertrophy or left atrial enlargement, elevated NT-proBNP, and optimised treatment of comorbidities [1]. The PARALLAX study also compared sacubitril/valsartan to individualised therapy but with a different co-primary endpoint. While PARAGON-HF assessed a composite of hospitalisation for heart failure and cardiovascular death, PARALLAX assessed the biomarker NT-proBNP and 6-minute walk test, since loss of exercise capacity is a key indicator of heart failure.
Results of the PARALLAX study were presented by principal investigator Prof. Burkert Pieske (Charité University Medicine Berlin, Germany). At 12 weeks, sacubitril/valsartan was associated with a 16% greater reduction in NT-proBNP level compared with individualised medical therapy, including the angiotensin-converting enzyme (ACE) inhibitor enalapril, the angiotensin receptor blocker valsartan, or placebo (adjusted geometric mean ratio 0.84; P<0.0001; see Figure). At week 24, no significant difference was observed in the second co-primary endpoint, the 6-minute walk distance (adjusted mean difference -2.5 m; P=0.42). In accordance with this, there was also no significant difference in secondary endpoints, i.e. change of Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary scores (least square means difference 0.52; P=0.48) or NYHA class (OR 1.01; P=0.93), between the study arms at week 24.
Figure: Primary outcomes of PARALLAX [1]
IMT, individualised medical therapy; NT-proBNP, N-terminal pro-b-type natriuretic peptide; S/V, sacubitril/valsartan.
Post-hoc and exploratory analyses
A post-hoc analysis of the PARALLAX trial, comparing data from the study drug and placebo groups, showed that patients in the sacubitril/valsartan group had a 51% reduced risk of first hospitalisation due to heart failure at 24 weeks (HR 0.49; P=0.005). Also, the composite endpoint of time to death due to heart failure or heart failure hospitalisation in days was in favour of the study drug (HR 0.64; P=0.034).
However, a prespecified exploratory analysis of renal impact suggested sacubitril/valsartan was associated with a decline in estimated glomerular filtration rate (eGFR) compared with individualised medical therapy over 24 weeks (adjusted mean difference 1.10 mL/min/1.73 m2).
- Pieske B. PARALLAX: Sacubitril/valsartan versus individualized RAAS blockade in patients with HFpEF. Hot Line 2 session, ESC Congress 2020, 30 Aug.
- Solomon SD, et al. N Engl J Med 2019; 381:1609-1620.
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Table of Contents: ESC 2020
Featured articles
2020 ESC Clinical Practice Guidelines
2020 Atrial Fibrillation Guidelines
2020 Non-ST-Segment Elevation Acute Coronary Syndromes Guidelines
2020 Sports Cardiology and Exercise in Cardiovascular Patients Guidelines
2020 Adult Congenital Heart Disease Guidelines
Hot Line Presentations
SGLT2 inhibitor improves cardiovascular outcomes in heart failure patients
First-in-class cardiac myosin inhibitor effective in obstructive hypertrophic cardiomyopathy
Reduced cardiovascular outcomes with early rhythm control
Trimetazidine after successful PCI not associated with fewer cardiac events
POPular TAVI: Aspirin-only antiplatelet strategy?
Reduced NT-proBNP in HFpEF with sacubitril/valsartan
DAPA-CKD: Dapagliflozin improves CKD survival ± diabetes
Low-dose colchicine reduces CV death and ischaemic events in coronary disease
Similar outcomes sPESI and HESTIA for pulmonary embolism triage
Antihypertensives also reduce CV risk in people with normal blood pressure
COVID-19: Continuing versus suspending ACE inhibitors and ARBs
Drug initiation strategy not associated with increased use of oral anticoagulants
Restrictive blood transfusion non-inferior and cost-effective strategy
Late-Breaking Science
Increased mortality with colchicine in patients with ACS
Rivaroxaban protects limbs and ischaemic events in CAD-PAD patients
Antisense APOC3 oligonucleotide lowers triglyceride and atherogenic lipoproteins
Antisense ANGPTL3 lowers triglycerides
Reduced progression of coronary atherosclerosis with icosapent ethyl
Digoxin improves symptoms in stable patients with permanent AF
SGLT2 inhibitor ertugliflozin shows similar mortality but fewer HF hospitalisations
COVID and Cardiovascular Disease
Risk factors for thromboembolism and bleeding in COVID-19: lessons from Wuhan
The Yale COVID-19 Cardiovascular Registry
COVID-19 treatments and the importance of randomised trials
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