SPC365

The effect of heart failure therapy in patients with mildly reduced ejection fraction: a network meta-analysis

Session: Comunicações Orais (Sessão 12) - Insuficiência Cardíaca 2 - Tratamento
Speaker: Marta Leite

Congress: CPC 2022
Topic: D. Heart Failure
Theme: 10. Chronic Heart Failure
Subtheme: 10.4 Chronic Heart Failure – Treatment
Session Type: Comunicações Orais
FP Number: ---
Authors: Marta Leite; Francisco Sampaio; Francisca A.Saraiva; Sílvia O.Diaz; António S.Barros; Ricardo Fontes-Carvalho
<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial"><u>Background:</u></span></span><span style="font-size:12pt"><span style="font-family:Arial"> Recent 2021 heart failure (HF) guidelines have renamed patients with left ventricular ejection fraction (LVEF) between 41%-49% as heart failure with mildly reduced ejection fraction (HFmrEF). HFmrEF treatment is often considered a gray zone as there are no RCTs conducted exclusively in these patients.</span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial"><span style="background-color:#ffffff">Network meta-analysis is a new statistical </span></span></span><span style="font-size:12pt"><span style="font-family:Arial"><span style="background-color:#ffffff">technique</span></span></span><span style="font-size:12pt"><span style="font-family:Arial"><span style="background-color:#ffffff"> </span></span></span><span style="font-size:12pt"><span style="font-family:Arial"><span style="background-color:#ffffff">that compares several interventions simultaneously in a single analysis by combining both direct and indirect evidence across a network of studies.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial"><u>Aim:</u></span></span><span style="font-size:12pt"><span style="font-family:Arial"> To evaluate and compare the relative efficacy of</span></span><span style="font-size:12pt"><span style="font-family:Arial"> spironolactone (MRA), candesartan (ARB), sacubitril-valsartan (ARNI), and beta-blockers (BB) </span></span><span style="font-size:12pt"><span style="font-family:Arial"><span style="background-color:#ffffff">in </span></span></span><span style="font-size:12pt"><span style="font-family:Arial">HFmrEF.</span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial"><u>Methods:</u></span></span><span style="font-size:12pt"><span style="font-family:Arial"> RCTs evaluating</span></span><span style="font-size:12pt"><span style="font-family:Arial"> </span></span><span style="font-size:12pt"><span style="font-family:Arial">the efficacy of pharmacological treatments in HF that included patients with LVEF between 40%-50% were searched. Hazard ratio (HR) was extracted from each subanalysis for intervention versus placebo. A fixed and random-effects network meta-analysis was performed using </span></span><span style="font-size:12pt"><span style="font-family:Arial"><em>R </em></span></span><span style="font-size:12pt"><span style="font-family:Arial">statistical software</span></span><span style="font-size:12pt"><span style="font-family:Arial"><em>. </em></span></span><span style="font-size:12pt"><span style="font-family:Arial">The three outcomes analyzed were a composite of cardiovascular death and HF hospitalizations, cardiovascular death, and HF hospitalizations.</span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial"><u>Results</u></span></span><span style="font-size:12pt"><span style="font-family:Arial">: From the literature, we found four RCTs with </span></span><span style="font-size:12pt"><span style="font-family:Arial">subgroup </span></span><span style="font-size:12pt"><span style="font-family:Arial">analysis according to participants&rsquo; ejection fraction (TOPCAT, CHARM, PARADIGM/PARAGON), and </span></span><span style="font-size:12pt"><span style="font-family:Arial"><span style="background-color:#ffffff">an individual patient-level analysis of double-blind randomized trials</span></span></span><span style="font-size:12pt"><span style="font-family:Arial"> of BB (BB-HCFG). A total of 3844 patients were included</span></span><span style="font-size:12pt"><span style="font-family:Arial">.&nbsp;</span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial">There is a significant reduction of events with pharmacological treatment compared with placebo in the composite endpoint (ARNI vs. placebo: HR 0.62, 95% CI 0.45-0.85; ARB vs. placebo: HR 0.76, 95% CI 0.61-0.94) and in HF hospitalizations (BB vs. placebo: HR 0.48, 95% CI 0.24-0.95).</span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial">We did not observe a statistically significant difference in any comparisons between treatments (indirect comparisons), which suggests a similar magnitude of effect. Nevertheless, there wa</span></span><span style="font-size:12pt"><span style="font-family:Arial">s </span></span><span style="font-size:12pt"><span style="font-family:Arial">a sound reduction of the composite endpoint with ARNI (HR vs. BB: 0.74, 95% CI 0.47-1.16; HR vs. MRA 0.86, 95% CI 0.53-1.38). Although BB w</span></span><span style="font-size:12pt"><span style="font-family:Arial">ere globally less beneficial in the</span></span><span style="font-size:12pt"><span style="font-family:Arial"> </span></span><span style="font-size:12pt"><span style="font-family:Arial">composite endpoint and cardiovascular death, they seemed to be more effective in reducing HF hospitalizations</span></span><span style="font-size:12pt"><span style="font-family:Arial"> </span></span><span style="font-size:12pt"><span style="font-family:Arial">(HR vs. ARB: 0.59, 95% CI 0.28-1.25; HR vs. MRA: 0.70, 95% CI 0.30-1.60; HR vs. ARNI: 0.62, 95% CI 0.28-1.40).&nbsp;</span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Arial"><u>Conclusion:</u></span></span><span style="font-size:12pt"><span style="font-family:Arial"> Pharmacological treatment recommended for reduced LVEF can also be effective in HFmrEF. This network meta-analysis did not show significant superiority of any pharmacological class compared to the others.</span></span></p>