Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF

Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. URL: https://clinicaltrials.gov Unique Identifier: NCT01920711

Effects of serelaxin in patients with acute heart failure

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. Results: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. Conclusions: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.

Are all biopsies created equal? comparison of extended sextant prostate biopsies performed with and without MRI-TRUS fusion biopsy system.

117 Background: Extended sextant systematic prostate biopsies have the inherent risk of under-sampling prostate cancer. Fusion guided multiparametric magnetic resonance imaging (mpMRI) biopsies have been employed to better represent the disease and guide treatment. We sought to determine if due to heightened suspicion of cancer and/or visualization of mpMRI there were any discrepancies between systematic biopsies done with a Fusion System as compared to those done without (TRUS alone). Methods: From a prospectively collected database, we performed a review collecting age, race, clinical stage, PSA, and time until repeat systematic biopsy as part of fusion guided biopsy (IB). We also collected pathology results reported as Gleason Score (GS), for both the patients’ OB and our IB. Patients were stratified into groups based on time between OB and IB/fusion biopsy ( &lt; 6 months, &lt; 1 year and &lt; 2 years). Results: 69 patients with a previous OB underwent combined fusion and IB within our designated time intervals. Cancer detection rates between the OB and IB results were similar at 6 months, 1 year and 2 years (80 vs 90%, 87.5 vs 87.5% and 65 vs 69%). Detection rates of GS ≥ 3+4 were higher with IB within 12 months compared with IB from 12-24 months (72.7 vs 40.9%, p = 0.03 OR 3.85 (1.09-13.66). Of the patients who were upgraded (n = 24), 54.2% (n = 13) went from benign pathology to a diagnosis of prostate adenocarcinoma. Of all OB GS 3+3 (n = 31), 29% were restaged to higher risk disease on IB. Rates of IB upgrading were similar within 6 months, 1 year and 2 year, 40%, 33.33% and 31.91%). Patients who were upgraded on IB compared to those who were not upgraded were of similar age (67.0 ± 6.53 vs 66.50 ± 6.47), race (17.4% African-American vs 13%), PSA (7.60 ± 5.61 vs 7.50 ± 4.39) and prostate volume on MRI (51.30 ± 26.87 vs 59.26 ± 38.52). Conclusions: A systematic biopsy at our referral center during a mpMRI fusion biopsy was over 3.5 times more likely to detect GS ≥ 3+4 when done within 1 year of the outside biopsy. There continued to be a risk, 34.7% overall, of disease upgrading in all time periods. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH </jats:p