SPC365

Effectiveness and safety of sacubitril/valsartan in patients with stage 4 chronic kidney disease in a real-world population

Session: Posters - D. Heart Failure
Speaker: Sara Couto Pereira

Congress: CPC 2021
Topic: D. Heart Failure
Theme: 10. Chronic Heart Failure
Subtheme: 10.4 Chronic Heart Failure – Treatment
Session Type: Posters
FP Number: ---
Authors: Sara Couto Pereira; João r. Agostinho; Tiago Rodrigues; Pedro Silvério António; Nelson Cunha; Joana Brito; Pedro Alves da Silva; Ana Margarida Martins; Joana Rigueira; Rafael Santos; Nuno Lousada; Fausto j. Pinto; Dulce Brito
<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="font-size:11pt"><span style="color:black">Introduction:&nbsp;</span></span></strong><span style="font-size:11pt"><span style="color:black">The PARADIGM-HF Trial showed that Sacubitril/valsartan (S/V) reduced mortality and hospital admissions when compared to enalapril in patients (pts) with heart failure with reduced ejection fraction (HFrEF). However, pts with estimated glomerular filtration rate (eGFR) &lt;30mL/min/1.73m<sup>2</sup>&nbsp;were excluded from the trial and data regarding effectiveness and safety of S/V in this subgroup of pts is scarce.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="font-size:11pt"><span style="color:black">Purpose:</span></span></strong><span style="font-size:11pt"><span style="color:black">&nbsp;To evaluate the effectiveness and safety of S/V in pts with CKD stage 4 in a HFrEF real-world population. </span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="font-size:11pt"><span style="color:black">Methods:</span></span></strong><span style="font-size:11pt"><span style="color:black">&nbsp;&nbsp;Nested case control study of HFrEF pts on S/V followed in a Heart Failure Clinic. The study group (SG) was composed of pts with eGFR&lt;30mL/min/1.73m<sup>2</sup>&nbsp;before starting S/V and the control group (CG) was composed of pts with eGFR&gt;30mL/min/1.73m<sup>2</sup> at the same time frame, matched for NYHA functional class, left ventricular ejection fraction (LVEF), age, NT-proBNP and HFrEF etiology. A ratio of 2 CG pts to 1 SG pt was used.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="font-size:11pt"><span style="color:black">Pts with CKD stage 5 (&lt;15 mL/min/1.73m<sup>2</sup>) were excluded. Effectiveness was evaluated by improvement in NYHA class, LVEF and HF admissions and death rates reduction. Follow up time was 617 (279-855) days. The safety outcome was defined by any adverse event leading to drug discontinuation.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="background-color:white"><strong><span style="font-size:11pt"><span style="color:black">Results:&nbsp;</span></span></strong><span style="font-size:11pt"><span style="color:#222222">From a cohort of 191 HFrEF pts on S/V, </span></span><span style="font-size:11pt"><span style="color:black">13 pts with eGFR&lt;30 and &gt;15mL/min/1.73m<sup>2</sup>&nbsp;were identified (76.9% men; median age 71 IQR 67.5-77; 53.8% NYHA II; median LVEF 28% IQR 21-30.5). The CG had 26 pts (92.3% men; median age 69.5 IQR 66-77.5; 57.7% NYHA II; median LVEF 30% IQR 25-34; 50% had CKD stage 3). There were no significant differences regarding </span></span><span style="font-size:11pt"><span style="color:black">NYHA class, LVEF, age, NT-proBNP or HFrEF etiology</span></span><span style="font-size:11pt"><span style="color:black"> (p=NS). </span></span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="background-color:white"><span style="font-size:11pt"><span style="color:black">There was a similar LVEF</span></span><span style="font-size:11pt"><span style="color:black"> and NYHA class</span></span><span style="font-size:11pt"><span style="color:black"> improvement</span></span> <span style="font-size:11pt"><span style="color:black">in both groups (p=NS)</span></span><span style="font-size:11pt"><span style="color:black">. There were no differences regarding acute HF or all-cause hospital admissions (p=0.676) or mortality (2 SG pts died vs. 3; p=0.691).</span></span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="font-size:11pt"><span style="color:black">During follow-up, there were significantly higher rates of S/V withdrawal in the SG (5 (38.5%) vs. 2 pts (7.7%); p=0.018). The most common S/V drug withdrawal cause in the SG was symptomatic hypotension (4&nbsp;vs. 0 pts). However, there were no significant differences between the 2 groups (p=NS) regarding systolic blood pressure either at baseline, after S/V initiation or after achieving S/V maximum tolerated dose. Interestingly, only 1 pt in the SG withdrew S/V therapy due to worsening renal function. Hyperkalemia was not the cause of S/V discontinuation in neither group.&nbsp;</span></span></span></span></span><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="font-size:11pt"><span style="color:black">Maximum tolerated doses of S/V were significantly lower in the SG (5 pts (38.5%) with 24/26 mg vs. 11 pts (42.3%) with 49/51 mg in CG; p=0.012).&nbsp;</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="font-size:11pt"><span style="color:black">Conclusion:&nbsp;</span></span></strong></span></span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">In this small real-life study, we found that S/V seems to be effective and may be safe to use in pts with CKD stage 4 if rigorous monitoring of potential adverse effects is secured. Although there was more drug utilization limiting adverse effects in these pts, there were no differences in prognostic impactful events. Larger studies are needed to confirm these results.</span></span></span></p>