SPC365

Sacubitril/valsartan in HFrEF patients with low NT-proBNP levels – any benefit?

Session: CO 08 - Insuficiência cardíaca crónica
Speaker: Beatriz Valente Silva

Congress: CPC 2021
Topic: D. Heart Failure
Theme: 10. Chronic Heart Failure
Subtheme: 10.4 Chronic Heart Failure – Treatment
Session Type: Comunicações Orais
FP Number: ---
Authors: Beatriz Silva ; João Agostinho; Tiago Rodrigues; Nelson Cunha; Pedro Silvério António; Sara Couto Pereira; Joana Brito; Pedro Alves da Silva; Joana Rigueira; Nuno Lousada; Doroteia Silva; Fausto J.Pinto; Dulce Brito
<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Introduction: </span></span></strong><span style="font-size:11.0pt"><span style="color:black">PARADIGM-HF trial included patients (pts) with symptomatic heart failure (HF) with reduced ejection fraction (HFrEF) and NTproBNP levels above &gt;600 pg/mL or &gt; 400 pg/mL if they had been hospitalized for HF within the previous 12 months. Data regarding therapy with sacubitril/valsartan (S/V) in pts with lower NTproBNP are lacking.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Purpose:</span></span></strong><span style="font-size:11.0pt"><span style="color:black"> To evaluate the clinical and prognostic effects of S/V in patients with HFrEF and low NTproBNP.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Methods: </span></span></strong><span style="font-size:11.0pt"><span style="color:black">Nested case-control study of pts with HFrEF followed in&nbsp; HF Clinic and medicated with S/V. The study group (SG) was composed of pts with </span></span><span style="font-size:11.0pt"><span style="color:black">NTproBNP &lt;600 pg/mL or &lt; 400 pg/mL if they had been admitted due to HF in the 12 months previous to</span></span><span style="font-size:11.0pt"><span style="color:black"> S/V initiation; the control group (CG) was composed of pts with higher levels of NTproBNP. Groups were matched for NYHA, left ventricular ejection fraction (LVEF), age, estimated glomerular filtration rate (eGFR) and HF etiology. A ratio of 2 control group pts to 1 study group pt was used. The 2 groups were compared regarding clinical and prognostic variables&nbsp;after a follow up of 20&nbsp;&plusmn; 12&nbsp;months.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Results:&nbsp;</span></span></strong></span></span><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">27 patients in a cohort of 191 HFrEF patients medicated with S/V met the </span></span><span style="font-size:11.0pt"><span style="color:black">SG</span></span><span style="font-size:11.0pt"><span style="color:black"> criteria; the </span></span><span style="font-size:11.0pt"><span style="color:black">CG</span></span><span style="font-size:11.0pt"><span style="color:black"> included 54 patients from the same cohort. At baseline, there were no differences regarding age, NYHA, LVEF, eGFR and HF etiology. Male gender was more prevalent in both groups (74&nbsp;and 76%), median age was 65 years (</span></span><span style="font-size:11.0pt">IQR </span><span style="font-size:11.0pt">55-71) and </span><span style="font-size:11.0pt"><span style="color:black">67 years (</span></span><span style="font-size:11.0pt">IQR </span><span style="font-size:11.0pt">57-74), respectively, and </span><span style="font-size:11.0pt"><span style="color:black">median LVEF was </span></span><span style="font-size:11.0pt">28%(IQR 22-34) in the SG, and 30%(IQR 22-35) in the CG. The most frequent HF etiology was ischemic disease (59% in both groups). Most pts were in NYHA II (78&nbsp;vs&nbsp;82%).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt">The median NTproBNP levels were 337 (IQR 238-396) pg/mL in the SG and 1845 (IQR 1074-3251) pg/mL in the CG (p&lt;0,001). &nbsp;</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">Although no patients from the SG died during the follow-up (vs 7 pts in the control group), there were no significant differences regarding hospitalization or mortality rates (p=NS). LVEF improved similarly in both groups (8&nbsp;&plusmn; 9% vs 9&plusmn; 13%; p=0.712).</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">There was a clinically significant improvement in NYHA functional class in both groups, but this improvement was more pronounced in the SG (48% of patients improved 1 NYHA functional class; 4% improved 2 classes) in comparison to the CG (28% of patients improved 1 class only) - p=0.013. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">The safety profile of S/V was similar in both groups, with no differences in drug withdrawal between groups. A trend for higher doses of S/V use in the study group was observed: 16 (59%) pts in the SG tolerated 49/51 mg vs&nbsp;20 (37%) pts in the CG, although the dose of 97/103 mg was attained similarly in both groups [5(19%) pts in the SG vs&nbsp;12(22%) pts in the CG]. &nbsp;&nbsp;</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Conclusion:&nbsp;</span></span></strong></span></span><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">This study suggests that in patients with HFrEF, low levels of NTproBNP should not be used to define an indication to start S/V. Although not included in the ancillary trial (PARADIGM-HF), pts with low levels of NTproBNP&nbsp;showed a better functional improvement and attained prognostic benefit similar to pts with higher levels.</span></span></span></span></p>