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Background Most clinical data regarding the use of sacubitril-valsartan (SV) in patients with heart failure with reduce EF (HFrEF) come from clinical trials, while observational studies in real life are scarce. Purpose To analyse the efficacy, safety and tolerability of SV in patients with HFrEF in real life. Methods An analysis of the SAVE-RLife (SV Evidence in Real Life) study was performed. This is an observational and ambispective study that included all patients with HFrEF who started SV between SEP2016 and DEC2018. Results A total of 291 patients were included in the study with a median follow-up of 326 (169; 523). Mean age 66.16±11.8, 71 were women (24.4%), 209 patients started treatment at office (71.8%) and 82 during the admission (28.2%). The main aetiologies were ischemic heart disease (51.5%) and idiopathic dilated cardiomyopathy (35.4%). Comorbidities included: 71.5% hypertensive, 55.3% dyslipidemic, 37.1% AF and 44% T2DM. Baseline treatment included 85.9% beta-blockers, 87.2% ACEI or ARA-II, 65.6% MRA and 17.5% iSGLT2. After treatment start with SV, baseline and follow-up analytical parameters such as GFR, K+ levels and NT-BNP, and echo parameters of LV reverse remodeling were evaluated (Table 1). Improvement of the functional NYHA class (Figure 1) and reduction in the incidence of hospital admission or visits to emergency room (ER) were observed. Side effects were 16.2% acute renal failure, 9.3% symptomatic hypotension, 9.7% asymptomatic hypotension and 15.9% hyperkalemia. In 31 patients (11%) the drug was discontinued, one patient due to angioedema. 7.9% of patients died during follow-up, 7 of them due to HF (2.4%). Table 1 Before SV After SV P value Analytical data GFR (ml/min) 70.25±24.95 68.27±24.62 0.008 Serum K+(mEq/L) 4.53±0.50 4.71±0.456 <0.001 NT-proBNP (pg/ml) 2201 (846; 4664) 1146 (436; 2564) <0.001 Echocardiographic data LVEF (%) (n=84) 30.60±7.16 38.30±12.22 <0.001 LVED (mm) (n=72) 65.22±7.82 60.81±8.37 <0.001 PAPs (mmHg) (n=48) 44.48±13.03 37.52±12.25 0.002 MR (grade 1–4) (n=71) 1.83±0.91 1.38±0.90 <0.001 Clinical outcomes HF Hospital/ER Admission the year before (mean± SD) 0.79±1.09 0.41±0.963 <0.001 Predictors of clinical improvement Conclusions SV has shown to improve morbidity and mortality in patients with HFrEF by improving functional class, decreasing NT-proBNP levels and reducing admissions due to HF, without significant side effects. In our study SV improved LVEF and reverse remodeling echocardiographic parameters too.

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Background. Interferon alfa (IFN a) induces complete cytogenetic response (CCR) in small proportion of CML patients, with almost all of these patients still presenting BCR-ABL transcript at the molecular level, even after prolonged period of CCR. Imatinib mesylate induces CCR in a 60–80% of patients but a high percentage of these still show residual disease as detectable by RT-PCR, and can be at risk of disease relapse. Thus combining synergistic drugs might be required to eliminate the disease effectively. Methods. We treated with imatinib 16 CML patients (8 M and 8 F) who were in very late CP and in stable CCR achieved with IFNa, but still were persistently positive at molecular level by RT-PCR. According to Sokal’s score, 11 patients were low risk (LR) and 5 were intermediate risk (IR). Median time from diagnosis was 125 mos.(r. 52–202), median duration of stable CCR was 79 mo.s (r.9–148). Imatinib was administered at the standard dose of 400 mg/die, after stopping IFN for 1 week. The level of residual disease was then monitored on BM cells at planned intervals ( baseline, 3, 6, 12 mo.s), by assaying BCR-ABL transcript at nested PCR and real-time quantitative RT-PCR; ABL was used as an internal control and results expressed as a ratio of BCR-ABL/ABL transcripts on a log scale. Results. The median transcript levels, as measured at various time points, appeared to progressively and consistently decrease in all patients with respect to the baseline values. In particular, BCR-ABL transcript undectectability was observed in 6/15 patients with evaluable analyses at 3 mo.s, in 9/16 patients analysed at 6 mo.s, and in 5/8 with available results also at 12 mo.s; of these latter patients, 4 were already negative in previous analyses and one become negative at 12 mo.s. Thus, altogether, 10/16 (62.5%) patients with at least two examinations within 12 mo.s had at least one negative molecular result. Correlations between degree of transcript reduction and clinical/biological factors detected at diagnosis and during follow-up, evidenced not significant results for age, type of transcript (either b2a3 or b3a3), baseline transcript level pre-imatinib, duration of disease and of stable CCR prior imatinib, while a trend was apparent for a higher rate of LR vs IR score among the 10 patients reaching transcript undetectability (8/10 LR vs 2/10 IR) with respect to the 6 persistently positive subjects(3 LR vs 3 IR). In present cases, imatinib was well tolerated and no side effects required drug dose reduction or discontinuation. At a median follow-up of 13 months (8–16) from start imatinib, all 16 patients are alive in CCR with progressively improving molecular response, 10 of whom with persistent transcript undetectability. Conclusion. Albeit obtained in a series of very selected patients, present results represent a further evidence stressing on the efficacy of combining imatinib and IFN a; through different, possibly complementary, mode of action, these two drugs might mutually potentiate their effect while reducing the emergence of drug resistance. The additive toxicity caused by their concurrent use might be overcome by a sequential combination; this could also be applied to patients reaching stable CCR on imatinib but still maintaining detectable residual disease.