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Background and Aims Neprilysin inhibition (NEPi) combined with a renin-angiotensin system (RAS) blocker has been shown to play an important role among patients with heart failure (HF), whose main cause of inpatient admission is congestion, reducing effectively HF hospitalization and cardiovascular death. These benefits stem from NEPi being a natriuresis and diuresis factor while RAS, which activates subsequently, staying blocked. Thanks to this, sacubitril/valsartan is a promising tool targeting patients with chronic kidney disease (CKD) and HF, which frequently coexist and lead one to the other, challenging their management. There is evidence NEPi-RASb may be beneficial in this population but long-term outcome still lacks. The primary aim is to analyse potential improvement in HF and advanced CKD. Secondary, to evaluate the tolerability and safety profile in this population. Method A prospective observational study, conducted from October 2016 to December 2020. Twenty-five patients were included meeting the following criteria: diagnosis of HF plus reduced left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class of II-IV with indication of sacubitril/valsartan, and CKD stages 3-4. All of them were followed periodically by a Nephrologist at our Department. Results The male:women ratio was 4:21, with a mean age of 73.2 ± 5.9 years. All patients had diagnosed hypertension, 32% type 2 diabetes, and 92% dyslipidemia. By December 2020, seven patients had completed three-year follow-up, whereas 17 were followed successfully through one year of treatment. Six patients died during the study (50% due to cardiovascular event, none due to renal malfunction), another discontinued treatment due to hypotension, and no patient started renal replacement therapy. The median of the studied time of treatment was 31 months (IQR 23.5 - 35). Cardiac and renal characteristics are listed in Table 1. At first year a significant improvement in LVEF was found (p=0.018). Although it is observed a tendency to this enhancement at second and third years, statistical analysis was not significative, arguably because a limited sample. Nonetheless, the number of visits to the Emergency Department (ED) regarding congestion symptoms were significantly reduced at these periods. More interesting, kidney function improved at first year when comparing serum creatinine (p=0.043) and eGFR (p=0.008), and this improvement stays in the long term at second and third years (p=0.019, p=0.046 respectively). There were no significant changes in potassium nor in blood pressure, still urine protein excretion was significantly higher at third year (p=0.043), understandable possibly due to hyperfiltration mechanisms and diabetic nephropathy progression. Conclusion Sacubitril/valsartan showed a long-term improvement in cardiac and kidney function, explaining a reduction in the number of visits to ED due to congestion and eventually a better quality of life. Besides, the improvement in kidney function cannot be totally understood in the context of enhanced LVEF at first year as this effect fades with time. Future research should explore this line.

BACKGROUND AND AIMS Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV), partly due to the vascular inflammation itself, the associated organic damage and the treatment [1]. AAV has been associated with traditional risk factors, such as hypertension (HTN), diabetes mellitus (DM) or impared renal function [2], which also contribute to accelerated atherosclerosis. However, there are not specific recommendations about CVD treatment in AAV patients [3], and the vascular risk scores used for general population have not been extrapolated yet. Our objective is to assess the frequency of cardiovascular events (CVE) and mortality in AAV patients and to explore the possible vascular risk factors (VRF) and the therapeutic intervention on them. METHOD A descriptive and retrospective study of a multidisciplinary cohort of AAV patients followed prospectively was performed in 12 hospitals of the 8 provinces of Autonomous Community of Andalusia. Factors that presumably may influence in CVD and mortality were collected. Two CV risk scores were measured [4, 5]. The presence of a strategy carried out by clinicians on CV risk was analysed according guides ESC/ESH and KDIGO guides. Data was analysed using Chi-square, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval. RESULTS A multicentre cohort of 220 AAV patients followed up from 1979 until June 2020 was studied, during a mean ± standard deviation follow-up of 96.79 ± 75.83 months. The mean age at diagnosis was 59.92 ± 16.25 years, 45% were female and all but one caucasians. Sociodemographic and clinical characteristics are shown in Table 1. After AAV diagnosis, 30/224 (13%) patients presented at least one CVE (Figure 1A and B), 37% IHD, 43% CVA and 50% PVD. Independent prognostic factors of CVE were age (HR 1.042, P = .005) and the presence of hypertension (HTN) 6 months after diagnosis (HR 4.641, P = .01). Regarding classic VRFs, 81% had HTN [33% already presented it before diagnosis and 48% after (35% in the first 6 months)]. Thirty-four patients presented DM at the end of following [12% already presented it before diagnosis and 22% presented it after (16% in the first 6 months)]. The independent predictor for HTN at 6 months was renal involvement at BVAS baseline, and DM in the first 6 months for HTN at the end of following. Attending to the ESC Vascular Risk scale, 8.4% presented low risk, 16.9% moderate, 29.8 high and 44.4% very high risk. According to the REGICOR scale, the mean value of suffering a CV event in the next 10 years was 4.6%±3.32%, with 59%, 34% and 7% of patients presenting low, moderate and high risk, respectively. Regarding VRF management strategies, just 14% of hypertensive patients, 16.2% of those that needed dyslipidemia treatment, and 8.6% of diabetic patients were not within the target guidelines recommendations. Fifty-one patients (23%) died (Figure 1C and D), 23.5% due to infectuous disease, 19.6% to cancer, 17.6% to CVD,13.7% to AAV relapse and 13 due to organic deficit, other or an unknown cause. In our final model of multivariate analysis, just age and renal function at baseline were independent predictors of mortality. Independent prognostic factors of mortality were age (HR 1.083, P = .00) and baseline creatinine (HR 4.41, P = .01). CONCLUSION Age and early HTN are risk factors for having a CVE, and age and renal function are predictors of mortality. HTN are more frecuent in AAV patients than in general population. CVD screening in AAV patients is demanded. The REGICOR and ESC scores could be extrapolated as a predictor of cardiovascular risk in AAV patients.