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ahajournals.org
Introduction and methods
Treatment with sacubitril/valsartan has resulted in improved outcomes in HFrEF patients. Although therapies that improve prognosis in HFrEF usually result in reverse cardiac remodeling [1], mechanisms of benefit by sacubitril/valsartan remain elusive. The PROVE-HF trial demonstrated that treatment with sacubitril/valsartan resulted in significant reduction of NT-proBNP and that both magnitude and speed of NT-proBNP reduction were associated with reverse modeling [2].
This analysis of PROVE-HF examined whether achievement of an above-average rate of change in NT-proBNP at 3 months and LV end-systolic volume index (LVESVi), which is a key index of remodeling, at 6 months was associated with outcomes between 6 and 12 months.
Participants without events at 6 months and with echocardiograms at baseline and 6 months were included (n=638). Outcomes of interest were HF hospitalization and death. Patients were grouped based on extent of change in each measure (above vs. at/below 95% CI lower bound for the linear slope).
Main results
- Event rates from month 6 to 12 were lower in patients with above-average reduction for NT-proBNP and LVESVi, intermediate for those with above-average reduction for at least 1 measure and events were highest in those with at/below-average reduction of NT-proBNP and LVESVi.
- After adjustment for demographics, outcomes were significantly higher for patients at/below-average linear slopes for both measures compared to patients above-average linear slopes for both measures (OD 2.03, 95%CI:1.25-3.30, P<0.001).
Conclusion
Achieving at/below reduction of measures of reverse cardiac remodeling with sacubitril/valsartan was associated with increased risk of outcomes in HFrEF patients compared to those patients who achieved above-average reduction of measures. These results indicate that more rapid and robust reduction of NT-proBNP and LVESVi might identify patients with reverse cardiac remodeling and thus more likely to benefit from therapy with sacubitril/valsartan.
References
1. Kramer DG, Trikalinos TA, Kent DM, et al. Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a meta-analytic approach. J Am Coll Cardiol. 2010;56:392–406. doi: 10.1016/j.jacc. 2010.05.011
2. Januzzi JL Jr, Prescott MF, Butler J,et al. Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril/valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA. 2019;322:1–11. doi:
10.1001/jama.2019.12821
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