Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction: protocol for a randomized controlled trial
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ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1000 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Background and purposePrevious studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI.MethodsIn a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge).ResultsWe evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05).ConclusionsSacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.
| S-EPMC10513241 | biostudies-literature
Project description:BackgroundNatriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and recommended.ObjectivesThe purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan.MethodsBNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF.ResultsMedian BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively).ConclusionsCirculating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).
| S-EPMC7955687 | biostudies-literature
Project description:High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the time of myocardial infarction (MI) are strong predictors of prognosis. However, whether their premorbid (before MI occurrence) levels are associated with prognosis after incident MI is unknown.MethodsIn 1,054 participants from the Atherosclerosis Risk in Communities Study with incident MI, we evaluated premorbid levels of hs-cTnT and NT-proBNP measured on median 5.8 (interquartile interval 3.0-11.5 [mean 5.5]) years prior to incident MI and their associations with subsequent composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI, heart failure, and stroke.ResultsDuring a median follow-up of 3.0 years after MI, 801 participants developed the composite outcome. Both hs-cTnT and NT-proBNP were independently associated with the composite outcome after incident MI. Among individual outcomes, all-cause mortality, cardiovascular mortality, and heart failure showed significant associations with both cardiac markers. Overall, NT-proBNP demonstrated a more evident relationship than hs-cTnT. Indeed, the addition of premorbid NT-proBNP alone, but not hs-cTnT alone, to conventional predictors at incident MI significantly improved risk prediction of the composite outcome after incident MI (Δc-statistic 0.013 [95% CI 0.005-0.022] from 0.691 with conventional predictors).ConclusionsPremorbid levels of hs-cTnT and NT-proBNP assessed on average 6 years prior to incident MI were associated with adverse outcomes after incident MI. These results further highlight the importance of cardiac health at an earlier stage of life.
| S-EPMC6842707 | biostudies-literature
Project description:BackgroundB-type natriuretic peptide (BNP) immunoassays (BNPia) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32.Methods and resultsWe developed a MS assay with immediate protease inhibition to quantify BNP1-32 over a linear range, using labeled recombinant BNP standard. In 4 healthy volunteers, BNP1-32 by MS (BNPMS) increased from below the 5 pg/mL detection limit to 228 pg/mL after nesiritide. In patients with HF, BNPMS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan treatment. BNPMS was 4.4-fold lower than BNPia in patients with HF. Among patients not taking sacubitril/valsartan and without end-stage renal disease, BNPMS correlated with BNPia (rs = 0.77, P < .001) and NT-proBNP (rs = 0.74, P < .001). After a median of 8 weeks on sacubitril/valsartan, active BNPMS levels decreased by 50% (interquartile range -98.3% to 41.7%, n = 22, P = .048) and correlated with NT-proBNP (rs = 0.64, P < .001), but not with BNPia (rs = 0.46, P = .057).ConclusionsActive BNP measured by MS accounts for only a small amount of BNP measured by immunoassays. Although decreased BNP production was anticipated to be masked by inhibition of degradation, levels of active BNP decreased during chronic sacubitril/valsartan treatment.
| S-EPMC8578199 | biostudies-literature
Project description:BackgroundDiffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD.MethodsRole of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan.DiscussionREVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.
| S-EPMC10478086 | biostudies-literature
Project description:Angiotensin-converting enzyme inhibitors and the angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI). Based on previous clinical trials, a maximum clinical dose is recommended in practical guidelines. Yet, has not been clearly demonstrated whether the recommended dose is more efficacious compared to the lower dose that is commonly used in clinical practice.Valsartan in post-MI remodeling (VALID) is a randomized, open-label, single-blinded multicenter study designed to compare the efficacy of different clinical dose of valsartan on the post-MI ventricular remodeling. This study also aims to assess neurohormone change and clinical parameters of patients during the post-infarct period. A total of 1116 patients with left ventricular dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to a maximal tolerable dose (up to 320 mg/day) or usual dose (80 mg/day) of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling is to be conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times.VALID is a multicenter collaborative study to evaluate the impact of dose of valsartan on the post-MI ventricular remodeling. The results of the study provide information about optimal dosing of the drug in the management of patients after MI. The results will be available by 2012.NCT01340326.
| S-EPMC3247852 | biostudies-literature
Project description:Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile. This review article will discuss the NPS, the failure of early drugs which targeted the NPS as therapies for HF, and the sequence of events which led to the development of sacubitril plus valsartan (Entresto; LCZ696; Novartis). LCZ696 has been shown to be superior to the standard of care available for treatment of HFrEF in several substantial hard endpoints including heart failure hospitalizations, cardiovascular mortality, and all-cause mortality.
| S-EPMC5575222 | biostudies-literature
Project description:BACKGROUND:Elevated postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are predictive for cardiac adverse events in noncardiac surgery. Studies indicate that supplemental oxygen decreases sympathetic nerve activity and might, therefore, improve cardiovascular function. Thus, we will test the effect of perioperative supplemental oxygen administration on NT-proBNP release after surgery. METHODS/DESIGN:We will conduct a single-center, double-blinded, randomized trial at the Medical University of Vienna, including 260 patients with increased cardiac risk factors undergoing moderate- to high-risk noncardiac surgery. Patients will be randomly assigned to receive 80% versus 30% oxygen during surgery and for 2?h postoperatively. The primary outcome will be the difference in maximum NT-proBNP release after surgery. As secondary outcomes we will assess the effect of supplemental oxygen on postoperative maximum troponin T concentration, oxidation-reduction potential, von Willebrand factor concentration and perioperative fluid requirements. We will perform outcome measurements 2?h after surgery, on postoperative day 1 and on postoperative day 3. The NT-proBNP concentration and the oxidation-reduction potential will also be measured within 72?h before discharge. DISCUSSION:Our trial should determine whether perioperative supplemental oxygen administration will reduce the postoperative release of NT-proBNP in patients with preoperative increased cardiovascular risk factors undergoing noncardiac surgery. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT03366857. Registered on 8th December 2017.
| S-EPMC7218565 | biostudies-literature
Project description:HIV-infected participants are at a higher risk for cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population and is associated with mortality in HIV.The 96-week Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial randomized 147 patients on stable antiretroviral therapy with low-density lipoprotein-cholesterol level lower than 130?mg/dl and without overt heart failure to 10?mg daily rosuvastatin or placebo. We measured NT-proBNP levels by enzyme-linked immunosorbent assay (ELISA). Baseline and changes in NT-proBNP were compared between groups. Spearman correlation was used to explore relationships between baseline NT-proBNP, inflammation, and CVD risk markers. Multivariable analyses were conducted to assess associations with NT-proBNP levels.Median age was 46 years, 80% were men, 69% were African American, and 46% were on protease inhibitors. At baseline, median (Q1, Q3) NT-proBNP was higher in the rosuvastatin group than placebo [41 (20, 66.5) versus 25?pg/ml (11, 56), P?=?0.012)]. Baseline NT-proBNP correlated with bulb and common carotid artery intima-media thickness, coronary calcium score, interleukin 6, and cystatin C. After 96 weeks, median NT-proBNP decreased significantly in the rosuvastatin group versus placebo (-1.50 versus +4.50?pg/ml, P?=?0.041). Within the rosuvastatin group, changes in NT-proBNP were negatively correlated with changes in insulin resistance and total limb fat.Rosuvastatin reduces plasma NT-proBNP in HIV-infected participants on antiretroviral therapy. NT-proBNP correlated with several measures of CVD risk, independent of inflammation markers.
| S-EPMC4405026 | biostudies-literature