- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Decongestion and Outcomes in Patients Hospitalized for Acute Heart (Pubmed Central) - Dec 1, 2024
P3
Among patients with AHF who were still hospitalized at day 5, residual congestion was common and independently associated with worse outcome. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778).
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Distinct Comorbidity Clusters in Patients With Acute Heart (Pubmed Central) - Oct 9, 2024
Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.
- |||||||||| Review, Journal: Clinical Management of Primary Aldosteronism: An Update. (Pubmed Central) - Aug 14, 2024
Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Atherothrombosis Intervention in High-Risk Patients Using Serelaxin), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal: Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue. (Pubmed Central) - Apr 22, 2024
(IL-1?), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date. (Pubmed Central) - Feb 23, 2024
A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Cardiovascular effects of relaxin-2: therapeutic potential and future perspectives. (Pubmed Central) - Sep 18, 2023
However, evidence from past clinical trials has been inconsistent and further research is needed to fully understand the potential applications of relaxin-2. This review provides an overview of serelaxin use in clinical trials and discusses future directions in the development of relaxin-2 mimetics, which may offer new therapeutic options for patients with heart failure.
- |||||||||| Reasanz (serelaxin) / Novartis
Presentation, clinical course and outcomes of women and men hospitalized with acute heart failure: insights from RELAX-AHF 2 trial (Moderated ePosters 1) - Feb 28, 2023 - Abstract #HEARTFAILURE2023HEART_FAILURE_697;
Purpose We sought to characterize the clinical phenotype, patient journey, and outcome of men and women with AHF enrolled in a large contemporary, multinational AHF trial, RELAX-AHF 2, the second seRELAXin in Acute Heart Failure trial...During hospital stay, women received lower doses of loop diuretics (120 vs 160 mg furosemide equivalent total intravenous cumulative diuretic dose through day 5, and 243 versus 280 mg furosemide equivalent total oral cumulative diuretic dose through day 5, both p 0.1) as compared to men...However, early incident WRF was more frequent in women and was associated with worse clinical outcomes, that were not observed in men or in women with no WRF through day 5. More studies are warranted to investigate sex differences in renal outcomes in AHF.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal, Combination therapy: Simultaneous late-gadolinium enhancement and T1 mapping of fibrosis and a novel cell-based combination therapy in hypertensive mice. (Pubmed Central) - Dec 13, 2022
This study thus, determined whether the anti-fibrotic drug, serelaxin (RLX), could enhance the therapeutic effects of BM-MSCs or BM-MSC-derived exosomes (BM-MSC-EXO) in hypertensive mice...On day 14 post-injury, subgroups of 1 K/DOCA/salt-hypertensive mice were treated with RLX alone or in combination with BM-MSCs or BM-MSC-EXO; or the mineralocorticoid receptor antagonist, spironolactone...It was concluded that the MP2RAGE sequence enhanced the non-invasive CMRI detection of LV fibrosis. Furthermore, combining RLX and BM-MSCs may represent a promising treatment option for hypertensive cardiorenal syndrome.
- |||||||||| Ventavis (iloprost) / Bayer, J&J, University of Copenhagen, Reasanz (serelaxin) / Novartis
Preclinical, Journal: In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions. (Pubmed Central) - Dec 13, 2022
Prostacyclin-mediated relaxation was evaluated by cumulative administration of iloprost (10-10M), a prostacyclin analog...Serelaxin exerts different effects via different mechanism on endothelium-dependent responses depending on the dose and duration of exposure. Therefore, proper timing and dosing of serelaxin administration in the penile tissue need to be investigated in further studies in diabetic animal models.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal: Optimization of an Ex-Vivo Human Skin/Vein Model for Long-Term Wound Healing Studies: Ground Preparatory Activities for the 'Suture in Space' Experiment Onboard the International Space Station. (Pubmed Central) - Nov 27, 2022
We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation...As a further clue about cell viability, some typical events associated with wound repair were observed in the tissue areas close to the wound, namely remodeling of collagen fibers in the papillary dermis and of elastic fibers in the vein wall, proliferation of keratinocyte stem cells, and expression of the endothelial functional markers eNOS and FGF-2. These findings validate the suitability of this new ex vivo organ culture system for wound healing studies, not only for the scheduled space experiment but also for applications on Earth, such as drug discovery purposes.
- |||||||||| TRV027 / Trevena, Reasanz (serelaxin) / Novartis
Biomarker, Journal: Neutrophil-to-Lymphocyte Ratio and Outcomes in Patients Admitted for Acute Heart Failure (As Seen in the BLAST-AHF, Pre-RELAX-AHF, and RELAX-AHF Studies). (Pubmed Central) - Sep 10, 2022
NLR was an independent predictor of 30-day all-cause mortality (adjusted hazard ratio [HR] per log NLR increment: 1.66 [1.22 to 2.25], p = 0.001), 60-day HF/renal failure rehospitalizations or CV death: 1.33 [1.12 to 1.57], p = 0.001), 180-day all-cause mortality (adjusted HR 1.27 [1.08 to 1.50], p = 0.003), and 180-day CV death (adjusted HR 1.24 [1.04 to 1.49], p = 0.018). NLR, a readily available inflammatory biomarker, was associated with independent risk for short- and long-term adverse outcomes in acute HF, surpassing traditional markers, such as natriuretic peptides.
- |||||||||| Reasanz (serelaxin) / Novartis
Biomarker, Review, Journal: Relaxin-2 as a Potential Biomarker in Cardiovascular Diseases. (Pubmed Central) - Jul 29, 2022
Furthermore, relaxin-2 has been proposed as a promising biomarker of cardiovascular health and disease. In this review, we emphasize the relevance of the endogenous hormone relaxin-2 as a useful diagnostic biomarker in different backgrounds of cardiovascular pathology, such as heart failure, atrial fibrillation, myocardial infarction, ischemic heart disease, aortic valve disease, hypertension, and atherosclerosis, which could be relevant in daily clinical practice and could contribute to comprehending the specific role of relaxin-2 in cardiovascular diseases.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Review, Journal: Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model. (Pubmed Central) - Jul 15, 2022
In this review, we emphasize the relevance of the endogenous hormone relaxin-2 as a useful diagnostic biomarker in different backgrounds of cardiovascular pathology, such as heart failure, atrial fibrillation, myocardial infarction, ischemic heart disease, aortic valve disease, hypertension, and atherosclerosis, which could be relevant in daily clinical practice and could contribute to comprehending the specific role of relaxin-2 in cardiovascular diseases. This new model, resulting from a combination of chronic and acute MI, and volume and pressure overload, was able to reproduce all the typical clinical signs occurring during ADHF in a consistent and reproducible manner.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Relaxin/serelaxin for cardiac dysfunction and heart failure in hypertension. (Pubmed Central) - Jun 8, 2022
We will also present evidence from pre-clinical animal studies that demonstrate the potential benefits of relaxin therapy, as well as discussing the results from clinical trials. Finally, we will discuss possible reasons for the failure of these clinical trials as well as steps being taken to potentially improve relaxin therapy for heart failure.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Human Recombinant Relaxin (Serelaxin) as Anti-fibrotic Agent: Pharmacology, Limitations and Actual Perspectives. (Pubmed Central) - Apr 13, 2022
In this review, we have summarized the molecular mechanisms of fibrosis, highlighting those which can be effectively targeted by relaxin. Then, we have performed a critical reappraisal of the clinical trials performed to-date with relaxin as anti-fibrotic drug, in order to highlight their key points of strength and weakness and to identify some future opportunities for the therapeutic use of relaxin, or its analogues, in fibrotic diseases and pathologic scarring which, in our opinion, deserve to be investigated.
- |||||||||| Reasanz (serelaxin) / Novartis
Distinct comorbidity clusters in patients with acute heart failure: data from RELAX-AHF-2 (ROOM 4) - Mar 12, 2022 - Abstract #HEARTFAILURE2022HEART_FAILURE_1011;
Treatment allocation (placebo or Serelaxin) modified the associations of multimorbidity groups with clinical outcome (Pinteraction< 0.001)...Comorbidities naturally clustered in 5 distinct patterns in RELAX-AHF-2, which show differences in clinical outcomes. These data highlight that the unique combination of comorbidities can drive adverse outcomes and treatment response in patients with AHF.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Relaxin as an anti-fibrotic treatment: perspectives, challenges and future directions. (Pubmed Central) - Mar 3, 2022
An emerging therapy that meets several criteria of an effective anti-fibrotic treatment, is the recombinant drug-based form of the human hormone, relaxin (also referred to as serelaxin, which is bioactive in several other species)...Studies that have compared and/or combined these therapeutic effects of relaxin with currently standard of care medication have also been discussed, along with the main challenges that have hindered the translation of the anti-fibrotic efficacy of relaxin to the clinic. The review then outlines the future directions as to where scientists and several pharmaceutical companies that have recognized the therapeutic potential of relaxin are working towards, to progress its development as a treatment for human patients suffering from various fibrotic diseases.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Cardioprotection Achieved Through Overexpression of Relaxin Receptors. (Pubmed Central) - Feb 8, 2022
The review then outlines the future directions as to where scientists and several pharmaceutical companies that have recognized the therapeutic potential of relaxin are working towards, to progress its development as a treatment for human patients suffering from various fibrotic diseases. No abstract available
- |||||||||| spironolactone / Generic mfg.
Preclinical, Journal: Comparing the renoprotective effects of BM-MSCs versus BM-MSC-exosomes, when combined with an anti-fibrotic drug, in hypertensive mice. (Pubmed Central) - Jan 27, 2022
To address this, we demonstrated that combining BM-MSCs with the anti-fibrotic drug, serelaxin (RLX), enhanced BM-MSC-induced renoprotection in preclinical CKD models...Subgroups of 1K/DOCA/salt-hypertensive mice were then treated with either RLX (0.5 mg/kg/day) or BM-MSC-EXO (25 μg/mouse; equivalent to 1-2 × 10 BM-MSCs/mouse) alone; combinations of RLX and BM-MSC-EXO or BM-MSCs (1 × 10/mouse); or the mineralocorticoid receptor antagonist, spironolactone (20 mg/kg/day), from days 14-21...Only RLX and BM-MSCs, but not RLX and/or BM-MSC-EXO, also attenuated the 1K/DOCA/salt-induced hypertension. Hence, although RLX improved the renoprotective effects of BM-MSC-EXO, combining RLX with BM-MSCs provided a better therapeutic option for hypertensive CKD.
- |||||||||| Reasanz (serelaxin) / Novartis, Esbriet (pirfenidone) / Shionogi, Roche
Journal: Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies. (Pubmed Central) - Nov 17, 2021
Among the anti-fibrotic compounds assessed, trichostatin A (inhibitors of histone deacetylases); serelaxin and pirfenidone (pleiotropic inhibitors of fibrotic activation); and soluble TGFβ receptor trap (inhibitor of TGFβ signalling) resulted in the highest decrease of collagen type I deposition (even higher than triamcinolone acetonide, the gold standard in clinical practice). This study further advocates the potential of macromolecular crowding in the development of in vitro pathophysiology models.
- |||||||||| Reasanz (serelaxin) / Novartis
Clinical, Journal: Cause of Death in Patients With Acute Heart Failure: Insights From RELAX-AHF-2. (Pubmed Central) - Sep 19, 2021
P3
Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778).
- |||||||||| Natrecor (nesiritide) / J&J, Reasanz (serelaxin) / Novartis
Review, Journal: Role of Vasodilator Therapy in Acute Heart Failure. (Pubmed Central) - Sep 18, 2021
These four trials have evaluated the efficacy of different types of vasodilators such as nesiritide, ulatritide, and serelaxin in the setting of AHF. Also, we compared comprehensive vasodilator therapy versus standard therapy to see if there is any effect on mortality and re-hospitalization.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Relaxin in hepatic fibrosis: What is known and where to head? (Pubmed Central) - Aug 7, 2021
Serelaxin, a recombinant human RLX-2 treatment has reduced hepatic fibrosis and portal hypertension in experimental models due to its vasodilation properties by inducing intrahepatic nitric oxide level...Though RLX has natural antifibrotic activity, its antifibrotic molecular mechanisms especially in hepatic fibrosis condition are not reported. This review exclusively focuses antifibrotic effect of RLX on hepatic fibrosis.
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