Timing of treatment optimisation after left ventricular assist device implantation: Insights from the ENVAD-HF trial
N Jakus, I Planinc, J J Brugts, B Claggett, U P Jorde, D Milicic, F Ruschitzka, N Uriel, P Rubis, L W Van Laake, I Rudez, M Hegarova, M R Mehra, S D Solomon, M CikesAbstract
Background
While guidelines suggest extension of heart failure-specific therapies after durable left ventricular assist device (LVAD) implantation, there are existing concerns of such interventions in the early postimplantation period. With this subanalysis of the ENVAD-HF trial, we aimed to examine the outcomes of patients depending on the timing of enrolment to the trial.
Methods
ENVAD-HF was a multinational, prospective, randomised, open-label trial, designed to explore the safety and the effect of sacubitril/valsartan (sac/val) on blood pressure management in LVAD carriers compared to standard of care. The primary endpoint was a composite of time to all-cause death, deterioration in renal function, hyperkalaemia or symptomatic hypotension. For this analysis, baseline data and outcomes were compared relative to the time of enrolment: recently implanted patients, enrolled during the LVAD implantation hospitalization (Recent) versus those enrolled after discharge, but within the first year after implantation (Chronic).
Results
Of the 60 randomized patients (mean age 57±12 years, 17% women), 20 (33%) were in the Recent and 40 (67%) in the Chronic group. In the Recent group, a larger proportion of patients were in higher INTERMACS profiles, without significant difference in the allocation to sac/val between groups (Table 1). The crude event rate of the primary outcome was higher in the Recent group: 24.0 (9.0-64.0) vs. 8.0 (2.6-24.9) per 100 person-years, without reaching statistical significance (HR 3.11, 95% CI 0.69-13.95, p=0.14) (Figure 1), and without quantifiable modification of the treatment effect of sac/val. A significant decrease of NT-proBNP from baseline to 8 weeks was noted in both groups (Recent: -55% (-72% to -27%), p=0.003; Chronic: -19% (-31% to -4%), p=0.015), with a 42% greater reduction in NT-proBNP in Recent vs. Chronic (ratio of 0.58 [95% CI: 0.39-0.87]; p=0.01), consistent after 6 months (ratio of 0.38 [95% CI: 0.24-0.60]; p<0.001) and 12 months (ratio of 0.60 [95% CI: 0.36-1.01]; p=0.056). A greater reduction in eGFR from baseline to month 12 was noted in the Recent vs. Chronic group (difference: -11.77 [95% CI -24.12 to 0.57], p=0.06), as well as a greater increase in the KCCQ-TSS from baseline to month 12 (difference: 7.85 [95% CI -0.73 to 16.42], p=0.07). Time of enrolment did not modify the treatment effect of sac/val on any of the tested outcomes (all interaction P values ≥0.35).
Conclusion
Recently implanted patients, who are at higher baseline risk, show higher crude event rates and larger biomarker shifts - a significantly greater reduction in NT-proBNP values vs. those enrolled as outpatients, without modification of the treatment effect of sac/val. Limited by natural post-implant trajectories and a small sample size, this post-hoc analysis suggests safety of early therapy optimisation.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.