C-reactive protein reduction with sacubitril-valsartan treatment in heart failure patients

摘要

Objective: C-Reactive Protein (CRP) has emerged as an accessible measured product of inflammation. Whether systemic inflammation, a common feature of Heart Failure (HF), can be reduced by HF treatments in not well established. Sacubitril/Valsartan had prognosis benefit demonstrated in the PARADIGM-HF trial and was able to reduce proinflammatory cytokines in preclinical animal studies. However, no human studies evaluated if the benefits of this therapy are mediated by anti-inflammatory effects too. The aim of this study was to prospectively compare CRP values before and six months after Sacubitril-Valsartan therapy. Methods: Prospective evaluation of chronic HF patients with left ventricular ejection fraction ≤ 40% despite optimized standard of care therapy, in which Sacubitril/Valsartan therapy was started and no additional HF treatment was expected to change. Clinical, laboratorial (including CRP values), electrocardiographic, transthoracic echocardiography and cardiopulmonary exercise test (CPET) data were gathered in the week before starting Sacubitril/Valsartan therapy and six months thereafter. Results: There were 42 patients with a mean age of 59 ± 11 years, of which 35 completed the six months of follow-up, since 2 patients died and 5 discontinued treatment for adverse events. Patients with baseline CRP values above the median ( 2.5 mg/L) had a significantly higher percentage of New York Heart Association class ≥ III (65% vs. 33%, P=0.028) and a reduced exercise time in CPET (361 ± 297 vs. 575 ± 265 seconds, P=0.034). After 6 months of Sacubitril-Valsartan therapy, 24 (69%) patients had an improvement in CRP values with a significantly reduction as compared to baseline (median 2.5 mg/L (Interquartile range (IQR) 1.3-5.0) vs. 2.2 mg/L (IQR 0.9-4.0), P=0.014 in the Wilcoxon test). In the group of 17 (49%) patients with at least 25% improvement in CRP values with Sacubitril/Valsartan therapy, the benefit of several clinical, CPET and echocardiographic parameters were not significantly different from the benefit of patients with no improvement or an improvement inferior to 25% in CRP values. Conclusion: Sacubitril/Valsartan therapy was able to reduce CRP values in a chronic HF population. Whether this reduction was only a consequence of clinical improvement with Sacubitril/Valsartan or an anti-inflammatory effect is also present should be further evaluated.