Association Between Sacubitril/Valsartan Use and Risk of Major Adverse Cardiovascular Events in Patients With Durable...

Durable left ventricular assist devices improve survival in patients with advanced heart failure (HF), yet long-term outcomes remain limited by recurrent decompensation and end-organ dysfunction. Evidence on the prognostic association of angiotensin receptor-neprilysin inhibitor (ARNI) therapy after left ventricular assist device implantation remains limited.

We conducted a retrospective multicenter cohort study using the TriNetX Research Network. Adults undergoing durable left ventricular assist device implantation between 2015 and 2025 were identified. Patients receiving ARNI therapy were propensity score matched 1:1 with patients without ARNI exposure. The primary outcome was 1-year major adverse cardiovascular events, defined as a composite of heart failure exacerbation or all-cause mortality. Secondary outcomes included all-cause mortality, heart failure exacerbation, and major adverse kidney events hazards models estimated hazard ratios (HRs) with 95% CIs.

After matching, 923 patients were included in each group. ARNI use was associated with significantly lower risks of major adverse cardiovascular events (28.8% versus 35.9%; HR 0.71, 95% CI 0.60-0.83; P<0.001), all-cause mortality (6.7% versus 10.6%; HR 0.57, 95% CI 0.41-0.78; P<0.001), heart failure exacerbation (26.0% versus 30.2%; HR 0.76, 95% CI 0.64-0.91; P=0.002), and major adverse kidney events (5.1% versus 10.4%; HR 0.45, 95% CI 0.32-0.64; P<0.001). Results were consistent across prespecified subgroups and supported by negative control and E-value analyses.

Among patients with durable left ventricular assist devices support, ARNI therapy was associated with lower cardiovascular and renal event risk. Given the observational design, these findings should be interpreted cautiously and require confirmation in prospective studies.