Association Between Sacubitril/Valsartan Use and Risk of Major Adverse Cardiovascular Events in Patients With Durable Left Ventricular Assist Devices: A Multi‐Institutional Real‐World Cohort Study

Q: What are the key findings of this study?

Sacubitril/valsartan use after durable LVAD implantation was associated with a lower 1-year risk of major adverse cardiovascular events compared to no ARNI use (28.8% vs 35.9%; HR 0.71, p<0.001).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Advanced heart failure with durable left ventricular assist device (LVAD) (n=1846). Intervention: Sacubitril/valsartan (ARNI) vs. No angiotensin receptor-neprilysin inhibitor (ARNI) exposure. Primary outcome: 1-year major adverse cardiovascular events (MACE), defined as a composite of heart failure exacerbation (HFE) or all-cause mortality (HR 0.71, 95% CI 0.60-0.83, p=<0.001).

Q: What does this research mean for the field?

Sacubitril/valsartan use after durable left ventricular assist device implantation is associated with a lower risk of 1-year major adverse cardiovascular events, all-cause mortality, and major adverse kidney events. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the association between angiotensin receptor–neprilysin inhibitor therapy and the risk of major adverse cardiovascular events in patients with durable left ventricular assist devices.

Jheng‐Yan Wu; Keng-Wei Lee; S H. M. Huang; Yu‐Min Lin

doi:10.1161/jaha.125.048550

July 10, 2026Journal of the American Heart AssociationOpen Access

Association Between Sacubitril/Valsartan Use and Risk of Major Adverse Cardiovascular Events in Patients With Durable Left Ventricular Assist Devices: A Multi‐Institutional Real‐World Cohort Study

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Key result

Post-LVAD sacubitril/valsartan is linked to ~29% lower 1-year MACE risk vs. non-use.

HR 0.71
95% CI 0.60-0.83
P<0.001
n=1,846

Why the study?

Evidence on the prognostic association of ARNI therapy after durable left ventricular assist device implantation remains limited.

Is post-implant sacubitril/valsartan (ARNI) therapy associated with a lower 1-year risk of major adverse cardiovascular events compared with no ARNI therapy in adults with durable left ventricular assist devices?

Key Points

To evaluate the association between angiotensin receptor–neprilysin inhibitor therapy and the risk of major adverse cardiovascular events in patients with durable left ventricular assist devices.
Retrospective multicenter cohort study using the TriNetX Research Network including adults undergoing durable left ventricular assist device implantation between 2015 and 2025.
Patients receiving ARNI therapy were propensity score matched 1:1 with patients without ARNI exposure, yielding 923 patients in each group.
The primary outcome was 1-year major adverse cardiovascular events (composite of heart failure exacerbation or all-cause mortality), with secondary outcomes of all-cause mortality, heart failure exacerbation, and major adverse kidney events.
ARNI use was associated with significantly lower risk of 1-year major adverse cardiovascular events compared with controls (28.8% versus 35.9%; HR 0.71, 95% CI 0.60–0.83; P <0.001).
Patients receiving ARNI therapy showed significantly lower rates of all-cause mortality (6.7% versus 10.6%; HR 0.57, 95% CI 0.41–0.78; P <0.001) and heart failure exacerbation (26.0% versus 30.2%; HR 0.76, 95% CI 0.64–0.91; P =0.002).
Major adverse kidney events occurred in 5.1% of patients in the ARNI group compared with 10.4% in the control group (HR 0.45, 95% CI 0.32–0.64; P <0.001).

Study Design

Type

Cohort (n=1,846)

Multicenter

Yes

Structured PICO

Is post-implant sacubitril/valsartan (ARNI) therapy associated with a lower 1-year risk of major adverse cardiovascular events compared with no ARNI therapy in adults with durable left ventricular assist devices?

P

Population

1,846 propensity-score matched adults (mean age ~54.5 years, 23.2% female) with advanced heart failure who underwent durable LVAD implantation between 2015 and 2025 across 158 institutions in the TriNetX network, followed for 1 year.

E

Exposure

Post-implant exposure to sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI], RxNorm 1656328) identified via electronic health record prescriptions.

C

Comparator

No ARNI prescription (patients excluded if ARNI prescriptions were identified from 12 months before through 12 months after cohort entry; matched 1:1 on demographics, comorbidities, lab values, and background HF medications including beta-blockers, RAS agents, MRAs, and SGLT2is).

O

Outcome

1-year major adverse cardiovascular events (MACE), defined as a composite of heart failure exacerbation (acute pulmonary edema or injectable diuretics) or all-cause mortality, assessed from 30 days to 1 year after cohort entry.composite

Main Result

Hazard Ratio: 0.71 (95% CI 0.6–0.83)

Absolute Event Rate: 28.8% vs 35.9%

p-value: p=<0.001

Limitations

Retrospective observational design using routinely collected electronic health records introduces potential residual confounding, selection bias, and incomplete capture of clinical variables.
Identification of exposures, covariates, and outcomes relied on structured coding and prescription documentation, which may result in misclassification.
Detailed treatment information including ARNI dose, duration, adherence, discontinuation, and exact clinical timing was unavailable.
Important measures of heart failure severity and device status (INTERMACS profile, hemodynamic parameters, right ventricular function, LVAD model) were not captured.
Substantial evolution in clinical practice and LVAD technology over the 2015-2025 study period.
Different cohort entry definitions between groups may introduce bias related to treatment timing and survivor effects.
Proportional hazards assumption was not fully satisfied (p=0.012) and cause-specific mortality was unavailable.
Retrospective observational design using electronic health records with potential for residual confounding and selection bias
Reliance on structured coding and prescription records without confirmation of medication dose, adherence, or persistence
Lack of data on specific LVAD models (e.g., HeartMate 3 vs HVAD), INTERMACS profile, hemodynamics, and right ventricular function
Different cohort entry definitions between exposed (first ARNI prescription) and unexposed (LVAD implantation date) groups
Proportional hazards assumption was not fully satisfied (P=0.012) and cause-specific mortality was unavailable

Implication

In a large multicenter cohort of patients with durable LVAD support, sacubitril/valsartan therapy was associated with significantly lower 1-year risks of major adverse cardiovascular events, mortality, heart failure exacerbation, and major adverse kidney events.

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Discussion

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Cite This Study

Wu et al. (2026) conducted a cohort in Advanced heart failure with durable left ventricular assist device (LVAD) (n=1,846). Sacubitril/valsartan (ARNI) vs. No angiotensin receptor-neprilysin inhibitor (ARNI) exposure was evaluated on 1-year major adverse cardiovascular events (MACE), defined as a composite of heart failure exacerbation (HFE) or all-cause mortality (HR 0.71, 95% CI 0.60-0.83, p=<0.001). Sacubitril/valsartan use after durable LVAD implantation was associated with a lower 1-year risk of major adverse cardiovascular events compared to no ARNI use (28.8% vs 35.9%; HR 0.71, p<0.001).

synapsesocial.com/papers/6a534ff4985393734a594d21 https://doi.org/10.1161/jaha.125.048550

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Association Between Sacubitril/Valsartan Use and Risk of Major Adverse Cardiovascular Events in Patients With Durable Left Ventricular Assist Devices: A Multi‐Institutional Real‐World Cohort Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Association Between Sacubitril/Valsartan Use and Risk of Major Adverse Cardiovascular Events in Patients With Durable Left Ventricular Assist Devices: A Multi‐Institutional Real‐World Cohort Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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