SPC365

Predictors of Maximal Dose Titration of Sacubitril-valsartan

Session: CO 10 - Insuficiência cardíaca crónica
Speaker: Ana Beatriz Garcia

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: Ana Beatriz Garcia; Ana Margarida Martins; Catarina Oliveira; Joana Brito; Beatriz Silva; Pedro Alves da Silva; Sara Couto Pereira; Pedro Silvério António; Nelson Cunha; Tiago Rodrigues; Joana Rigueira; João Agostinho; Nuno Lousada; Fausto j. Pinto; Dulce Brito

<p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Introduction:&nbsp;</strong></span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Sacubitril-valsartan S/V demonstrated a reduction in all-cause mortality and heart failure (HF) admissions in patients (pts) with reduced ejection fraction (HFrEF). However, achievement the same doses used on clinical trials can be difficult in real world practice. Little information is available on predicting which pts will achieve higher S/V doses.</span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Objective</strong>: to identify predictors of sacubitril/valsartan titration to the maximal dose. </span></span></p>

<p><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Methods</strong>: Retrospective single-center study of consecutive pts with HFrEF followed at an Ambulatory Heart Failure Clinic. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to find predictors of achieving the S/V maximal dose (97/103 mmHg bid). </span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Results</strong>:&nbsp;&nbsp;</span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">One hundred seventy-two pts were included, 80% (n=137) males, mean age 67 <span style="font-family:&quot;Times New Roman&quot;,serif">&plusmn;</span> 12 years, mostly with ischemic heart disease (55%) or dilated cardiomyopathy (36%) and in NYHA functional class II (71%). The mean left ventricular ejection fraction was 28<span style="font-family:&quot;Times New Roman&quot;,serif">&plusmn;</span>7%. The mean follow-up time was 632&nbsp;<span style="font-family:&quot;Times New Roman&quot;,serif">&plusmn;</span> 313 days.&nbsp;</span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Sixty-three patients (37%) achieved maximal dose of S/V, but only 26% (n=44) maintained that dose. Younger age (OR 0.97; p=0.030), acute <em>&ldquo;de novo&rdquo;</em> HF (OR 7.14; p&lt;0.001) and higher NYHA functional class (OR 1.92; p=0.036) was associated with achieving the maximal dose.&nbsp;</span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">On multivariate analyses, after adjusting for age, functional class, eGFR, systolic blood pressure, previous dose of angiotensin receptor blockers or angiotensin converting enzyme inhibitors, and acute <em>&ldquo;de novo&rdquo;</em> HF was found to be the only independent predictor of attaining maximal dose of S/V (OR=7.1, 95%IC 2.12- 23.04 p&lt;0.001). </span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Dose reduction was needed in 36 patients (21%). Symptomatic hypotension was the most common reason to reduce the dose (15%; n=18) and to completely withdraw S/V (10%; n=12). The other reasons that led to dose reduction were acutely decompensated HF, worsening renal function, cough and economic insufficiency (3.3%, 2.4%, 2.4% and 1.6%, respectively). Hyperkalemia led to dose reduction in 1 pt and no S/V withdrawal was due to this adverse effect.</span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Conclusion</strong>:&nbsp;&nbsp;</span></span><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="background-color:white"><span style="color:#212121">Sacubitril-valsartan was well tolerated and uptitration to the maximal dose of sacubitril/valsartan was possible in up to 37% of a real-world HFrEF cohort. Initiation sacubitril/valsartan during acute &ldquo;de novo&rdquo; Heart Failure phase independently predicts maximal dose achieving. Consequently, this study suggests that patients may attain higher benefit on initiating sacubitril/valsartan early after symptoms presentation. </span></span></span></span></p>