DOCSLIB.ORG

Comparative Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Heart Failure: a Network Meta-Analysis of Randomized Controlled Trials

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparative Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Heart Failure: a Network Meta-Analysis of Randomized Controlled Trials Heart Failure Reviews (2019) 24:637–646 https://doi.org/10.1007/s10741-019-09790-5 Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials Pingping Yang 1 & Wen Shen1 & Xi Chen2 & Dan Zhu1 & Xiuxiu Xu1 & Tao Wu1 & Gaosi Xu3 & Qinghua Wu1 Published online: 27 April 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P <0.01). This network meta-analysis is the first to find that finerenone 7.5–10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%. Keywords Heart failure . Mineralocorticoid receptor antagonists . Hyperkalemia . Meta-analysis Introduction development of HF, in which aldosterone plays an important role in mediating endothelial dysfunction, accelerating myocar- Heart failure (HF) is a major public health problem that repre- dial fibrosis, and subsequent cardiac remodeling [3, 4]. sents one of the leading causes of death worldwide [1, 2]. A Although an angiotensin-converting enzyme inhibitor (ACEI) variety of mechanisms are involved in the pathophysiological may reduce aldosterone for a short time, with chronic therapy, there is a rapid return of aldosterone to levels similar to those Pingping Yang and Wen Shen contributed equally to this work. before ACEI therapy, described as Baldosterone breakthrough^ Electronic supplementary material The online version of this article [5]. In addition to ACEI, mineralocorticoid receptor antagonists (https://doi.org/10.1007/s10741-019-09790-5) contains supplementary (MRAs), which have shown effects on lowering aldosterone material, which is available to authorized users. levels, may have potential benefits for HF patients [5]. Recently, steroidal MRAs, including spironolactone and * Qinghua Wu eplerenone, have been shown to have beneficial effects in [email protected] reducing cardiovascular mortality and hospitalizations in HF patients with an ejection fraction of no more than 35% [6–9]. 1 Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Donghu Hence, steroidal MRA therapy is recommended in the District, Nanchang 330006, Jiangxi, People’s Republic of China American and European guidelines for the treatment of HF 2 Department of Neurology, Huashan Hospital, Fudan University, with reduced ejection fraction (HFrEF) patients [10, 11]. Shanghai, China However, the high risk of adverse events associated with the 3 Department of Nephrology, The Second Affiliated Hospital of use of steroidal MRAs including hyperkalemia and renal de- Nanchang University, Nanchang, Jiangxi, China terioration was the main cause for their suboptimal use in 638 Heart Fail Rev (2019) 24:637–646 clinical practice, particularly in patients with chronic kidney no more than 45%, (b) study design was an RCT of the treat- disease (CKD) or type 2 diabetes mellitus [12–14]. ment group (MRAs) and control group, (c) studies with out- As a novel nonsteroidal MRA, finerenone is characterized comes of Bdeath from cardiac causes,^ Bhospitalization for by higher selectivity towards the mineralocorticoid receptor cardiac causes,^ Bthe number of patients with a decrease in (MR) and stronger MR-binding affinity than steroidal MRAs plasma NT-proBNP level of > 30%,^ Bhyperkalemia,^ [15]. Moreover, basic trials revealed that finerenone was as- Bworsening renal function,^ and/or Badverse event.^ sociated with decreasing levels of N-terminal pro-B-type na- The criteria for exclusion were as follows: (a) studies such triuretic peptide (NT-proBNP) and improving cardiac function as systemic reviews, comments, case reports, conference ab- via the binding mode of dihydropyridine-based L-type calci- stracts, and editorials; (b) subjects with a serum potassium um channel blockers to antagonize the MR in chronic HF level exceeding 5.5 mmol/l; and (c) articles that had no data models [16, 17]. In recent years, clinical researchers have on HF patients with an ejection fraction. investigated the efficacy and safety of finerenone [18–21]. Included trials reported comparisons of nine interventions However, a debate continues as to whether finerenone is ef- (placebo, spironolactone 25–50 mg, eplerenone 25–50 mg, fective and the optimal dose that exerts beneficial effects with the initial dose of finerenone with 2.5 mg, 5 mg, 7.5 mg, respect to decreasing plasma levels of NT-proBNP, the inci- 10 mg, 15 mg, canrenone 25–50 mg). NMA integrates data dence of cardiovascular mortality, hospitalizations, from direct comparisons of treatments within trials and from hyperkalemia, worsening renal function, and adverse events indirect comparisons of interventions assessed against a com- in chronic HF patients [18–21]. mon comparator in separate trials to compare all investigated Network meta-analysis (NMA) offers the potential to as- treatments. sess multiple therapeutic strategies simultaneously within a single framework and to rank treatments based on efficacy Data extraction and quality assessment and safety [22]. In the current paper, we conducted an NMA of randomized controlled trials (RCTs) for the first time to Two authors (Y-PP and S-W) extracted data and accessed explore the efficacy and safety of different doses of MRAs quality independently in an electronic database. The investi- in HF patients with an ejection fraction of no more than 45%. gators cross-checked the data and reached a consensus on any discrepancies through discussion. Disagreements were re- solved through discussions or referral to a third author (W- Methods QH). Reference lists of identified trials and review articles were manually scanned to identify related research references Data sources and search strategy at the same time as indicated in Fig. 1. The extracted data included the first author’s name, year of We conducted a systematic search of the period from January publication, kidney function, potassium level, sample size, 1, 1999, to December 1, 2018, without any language restric- doses of treatment, control, follow-up duration, the number tion, using PubMed, Embase, the Cochrane Library, and of patients, the outcomes of cardiovascular mortality, hospi- Clinicaltrials. We searched studies with key words and talizations, NT-proBNP level, hyperkalemia, worsening renal Medical Subject Headings that covered Bheart failure^ or function, and adverse events. Bsystolic heart failure^ or Bheart failure with reduced ejection fraction^ or BHF^ or BSHF^ or BHFrEF^ and Risk of bias assessment Bmineralocorticoid receptor antagonist^,orBMRA^ or Baldosterone receptor antagonist^ or Bspironolactone^ or Two independent reviewers (Y-PP and S-W) assessed the Bcanrenone^ or Beplerenone^ or Bfinerenone^ or BBAY 94- methodological quality of included trials using a slightly 8862.^ We also reviewed the corresponding reference list of adapted version of the risk of bias approach by using each retrieved article to identify any relevant studies that may Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) be neglected. The meta-analysis was conducted and reported risk of bias tool including four sections: selection, perfor- according to the Preferred Reporting Items of Systematic mance, detection, attrition, reporting, and other biases. The Reviews and Meta-Analyses (PRISMA) guidelines [23]. publication bias assessment was performed via Deek’sfunnel plot asymmetry. Selection criteria Statistical analysis We collected all RCTs to compare the therapeutic effects of differentMRAsinsystolicHFpatientswithanejectionfrac- The data were abstracted and analyzed by R software using tion ≤ 45% in this meta-analysis. Inclusion criteria of the stud- the Bgemtc^ package, STATA (version 14.0, Stata MP) and ies were as follows: (a) HF patients with an ejection fraction of WinBUGS (version 1.4.3, MRC Biostatistics Unit, Heart Fail Rev (2019) 24:637–646 639 Fig. 1 PRISMA diagram of the study selection process for the meta-analysis Cambridge, UK). The odds ratios (ORs) and their corre- Results
Load more

Recommended publications
  • Optumrx Brand Pipeline Forecast
    RxOutlook® 1st Quarter 2019 OptumRx brand pipeline forecast Route of Regulatory Estimated Specialty Orphan Drug name Generic name Company Drug class Therapeutic use administration status release date drug drug 2019 Possible launch date Ophthalmological DS-300 DS-300 Eton undisclosed SC Filed NDA 2019 unknown N disease anti-sclerostin Evenity romosozumab Amgen Osteoporosis SC Filed NDA 2/2019 Y N monoclonal antibody tetrahydrofolate iclaprim iclaprim Motif Bio Bacterial infections IV Filed NDA 2/13/2019 Y Y dehydrogenase inhibitor tazarotene/ IDP-118 Valeant retinoid/ corticosteroid Psoriasis TOP Filed NDA 2/15/2019 N N halobetasol adenosine deaminase Mavenclad cladribine Merck/ Teva resistant Multiple sclerosis PO Filed NDA 2/15/2019 Y N deoxyadenosine analog Lotemax Gel loteprednol Valeant corticosteroid Ocular inflammation OP Filed NDA 2/25/2019 N N Nex Gen etabonate turoctocog alfa glyco-PEGylated factor NN-7088 Novo Nordisk Hemophilia IV/SC Filed BLA 2/27/2019 Y N pegol VIII derivative selective sphingosine-1 BAF-312 siponimod Novartis phosphate receptor Multiple sclerosis PO Filed NDA 3/1/2019 Y N agonist midazolam midazolam UCB benzodiazepine Seizures Intranasal Filed NDA 3/1/2019 N Y (USL-261) XeriSol glucagon Xeris glucagon analog Diabetes mellitus SC Filed NDA 3/1/2019 N N Glucagon optum.com/optumrx 1 RxOutlook® 1st Quarter 2019 Route of Regulatory Estimated Specialty Orphan Drug name Generic name Company Drug class Therapeutic use administration status release date drug drug dopamine receptor JZP-507 sodium oxybate Jazz Narcolepsy
    [Show full text]
  • COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone During SARS-Cov-2 Infection
    pharmaceuticals Review COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection Katarzyna Kotfis 1,* , Kacper Lechowicz 1 , Sylwester Drozd˙ zal˙ 2 , Paulina Nied´zwiedzka-Rystwej 3 , Tomasz K. Wojdacz 4, Ewelina Grywalska 5 , Jowita Biernawska 6, Magda Wi´sniewska 7 and Miłosz Parczewski 8 1 Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland; [email protected] 2 Department of Pharmacokinetics and Monitored Therapy, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] 3 Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland; [email protected] 4 Independent Clinical Epigenetics Laboratory, Pomeranian Medical University, 71-252 Szczecin, Poland; [email protected] 5 Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] 6 Department of Anesthesiology and Intensive Therapy, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland; [email protected] 7 Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] 8 Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, 71-455 Szczecin, Poland; [email protected] * Correspondence: katarzyna.kotfi[email protected]; Tel.: +48-91-466-11-44 Abstract: In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared Citation: Kotfis, K.; Lechowicz, K.; a global pandemic by the World Health Organization (WHO). The clinical course of the disease is Drozd˙ zal,˙ S.; Nied´zwiedzka-Rystwej, unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to P.; Wojdacz, T.K.; Grywalska, E.; acute respiratory distress syndrome (ARDS).
    [Show full text]
  • Oregon Medicaid PA Criteria for Fee-For-Service Prescriptions
    Oregon Medicaid Pharmaceutical Services Prior Authorization Criteria HEALTH SYSTEMS DIVISION Prior authorization (PA) criteria for fee-for-service prescriptions for Oregon Health Plan clients March 29, 2017 Contents Contents ................................................................................................................................................................ 2 Introduction........................................................................................................................................................... 6 About this guide ......................................................................................................................................... 6 How to use this guide ................................................................................................................................. 6 Administrative rules and supplemental information .................................................................................. 6 Update information .............................................................................................................................................. 7 Effective March 29, 2017 .......................................................................................................................... 7 Substantive updates and new criteria ............................................................................................. 7 Clerical changes ............................................................................................................................
    [Show full text]
  • Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic Paradigm
    Kidney360 Publish Ahead of Print, published on July 23, 2020 as doi:10.34067/KID.0000922020 Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic Paradigm Michael R Lattanzio(1), Matthew R Weir(2) (1) Division of Nephrology, Department of Medicine, The Chester County Hospital/University of Pennsylvania Health System (2) Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD Correspondence: Matthew R Weir University of Maryland Medical Center Division of Nephrology 22 S. Greene St. Room N3W143 Baltimore, Maryland 21201 [email protected] 1 Copyright 2020 by American Society of Nephrology. Abbreviations PA=Primary Hyperaldosteronism CVD=Cardiovascular Disease PAPY=Primary Aldosteronism Prevalence in Hypertension APA=Aldosterone-Producing Adenoma BAH=Bilateral Adrenal Hyperplasia ARR=Aldosterone Renin Ratio AF=Atrial Fibrillation OSA=Obstructive Sleep Apnea OR=Odds Ratio AHI=Apnea Hypopnea Index ABP=Ambulatory Blood Pressure AVS=Adrenal Vein Sampling CT=Computerized Tomography MRI=Magnetic Resonance Imaging SIT=Sodium Infusion Test FST=Fludrocortisone Suppression Test CCT=Captopril Challenge Test PAC=Plasma Aldosterone Concentration PRA=Plasma Renin Activity MRA=Mineralocorticoid Receptor Antagonist MR=Mineralocorticoid Receptor 2 Abstract Nearly seven decades have elapsed since the clinical and biochemical features of Primary Hyperaldosteronism (PA) were described by Conn. PA is now widely recognized as the most common form of secondary hypertension. PA has a strong correlation with cardiovascular disease and failure to recognize and/or properly diagnose this condition has profound health consequences. With proper identification and management, PA has the potential to be surgically cured in a proportion of affected individuals. The diagnostic pursuit for PA is not a simplistic endeavor, particularly since an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm.
    [Show full text]
  • TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
    US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage .
    [Show full text]
  • Eplerenone Prevented Obesity- Induced Inflammasome Activation and Glucose Intolerance
    235 3 T WADA and others Eplerenone attenuates 235:3 179–191 Research chronic inflammation Eplerenone prevented obesity- induced inflammasome activation and glucose intolerance Tsutomu Wada1, Akari Ishikawa1, Eri Watanabe1, Yuto Nakamura1, Yusuke Aruga1, Hayate Hasegawa1, Yasuhiro Onogi1, Hiroe Honda2,3, Yoshinori Nagai2,4, Kiyoshi Takatsu2,3, Yoko Ishii5, Masakiyo Sasahara5, Daisuke Koya6, Hiroshi Tsuneki1 and Toshiyasu Sasaoka1 1Department of Clinical Pharmacology, University of Toyama, Toyama, Japan 2Department of Immunobiology and Pharmacological Genetics, University of Toyama, Toyama, Japan Correspondence 3Toyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan should be addressed 4JST, PRESTO, Saitama, Japan T Sasaoka or T Wada 5Department of Pathology, University of Toyama, Toyama, Japan Email 6Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan [email protected] or [email protected] Abstract Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated Key Words in the pathogenesis of insulin resistance; however, influences of mineralocorticoid f Endocrinology renin-angiotensin system of receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti- f glucose metabolism inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, f mineralocorticoid in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive receptor Journal body weight gain and fat accumulation, ameliorated glucose intolerance and insulin f NLRP3 inflammasome, adipose tissue macrophage resistance and enhanced energy metabolism. In the epididymal white adipose tissue (eWAT), eplerenone prevented obesity-induced accumulation of F4/80+CD11c+CD206−- M1-adipose tissue macrophage (ATM) and reduction of F4/80+CD11c−CD206+-M2-ATM. Interestingly, M1-macrophage exhibited lower expression levels of MR, compared with M2-macrophage, in the ATM of eWAT and in vitro-polarized bone marrow-derived macrophages (BMDM).
    [Show full text]
  • Cytochrome P450 3A Time-Dependent Inhibition Assays
    DMD Fast Forward. Published on April 2, 2021 as DOI: 10.1124/dmd.121.000356 This article has not been copyedited and formatted. The final version may differ from this version. Cytochrome P450 3A Time-Dependent Inhibition Assays are Too Sensitive for Identification of Drugs Causing Clinically Significant Drug-Drug Interactions: A Comparison of Human Liver Microsomes and Hepatocytes and Definition of Boundaries for Inactivation Rate Constants Heather Eng, Elaine Tseng, Matthew A. Cerny, Theunis C. Goosen, and R. Scott Obach Medicine Design, Pfizer Inc., Groton, Connecticut Downloaded from dmd.aspetjournals.org at ASPET Journals on September 27, 2021 Page 1 of 36 DMD Fast Forward. Published on April 2, 2021 as DOI: 10.1124/dmd.121.000356 This article has not been copyedited and formatted. The final version may differ from this version. Running title: Sensitivity of CYP3A Time-Dependent Inhibition Assays Corresponding authors: Heather Eng; Pfizer Inc., Eastern Point Road, Groton, CT 06340; [email protected]. R. Scott Obach; Pfizer Inc., Eastern Point Road, Groton, CT 06340; [email protected]. Number of text pages: 17 Number of tables: 2 Downloaded from Number of figures: 5 dmd.aspetjournals.org Number of references: 86 Number of words in Abstract: 217 Number of words in Introduction: 1289 at ASPET Journals on September 27, 2021 Number of words in Discussion: 1658 List of nonstandard abbreviations: ADME, absorption, distribution, metabolism, and excretion; AUCR, area under the plasma concentration-time curve ratio; CYP, cytochrome P450; DDI, drug-drug interaction; HHEP, human hepatocyte; HLM, human liver microsome; KI, inhibition constant; kinact, maximal rate of enzyme inactivation; kobs, rate constant for inhibition; LC-MS/MS, tandem liquid chromatography-mass spectrometry; M-I, metabolite-intermediate; m/z, mass to charge ratio; PBPK, physiologically based pharmacokinetic modeling; TDI, time-dependent inhibition; v/v, volume per volume ratio Page 2 of 36 DMD Fast Forward.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Randomized, Placebo-Controlled Trial of the Effects of Drospirenone
    Menopause: The Journal of The North American Menopause Society Vol. 14, No. 3, pp. 408/414 DOI: 10.1097/01.gme.0000243572.63322.f7 * 2007 by The North American Menopause Society Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide Richard A. Preston, MD, MSPH,1 Paul M. Norris, MD,2 Alberto B. Alonso, MD, PA,1 Pingping Ni, PhD,3 Vladimir Hanes, MD,3 and Adel H. Karara, PhD, FCP3 Abstract Objective: Drospirenone (DRSP), a spironolactone analog with aldosterone antagonist activity, is a novel progestogen developed for use as hormone therapy in postmenopausal women in combination with 17A-estradiol (E2). DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal women or when administered concomitantly with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. DRSP/E2 has not been studied in combination with the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when added to existing therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension. Design: This was a single-center, double-blind, randomized, placebo-controlled, two-treatment, two 4-week treatment period crossover study in 36 postmenopausal women with stage I hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring. Safety monitoring included serum potassium (mEq/L) and adverse events. Results: Mean systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were reduced significantly, by j7.2 and j4.5 mm Hg, respectively, with DRSP/E2 as compared with placebo.
    [Show full text]
  • The Use of a Novel Non-Steroidal Mineralocorticoid Receptor
    ® Systematic Review and Meta-Analysis Medicine OPEN The use of a novel non-steroidal mineralocorticoid receptor antagonist finerenone for the treatment of chronic heart failure A systematic review and meta-analysis ∗ Hui Pei, PhDa,d, Wei Wang, MDb, Di Zhao, MDc, Lei Wang, MDd, Guo-Hai Su, MDd, Zhuo Zhao, MDd, Abstract Background: The non-steroidal mineralocorticoid receptor antagonist finerenone (BAY 94–8862) has been used to treat chronic heart failure (CHF) with reduced ejection fraction (HFrEF). However, conflicting results were reported for its efficacy and safety. The study aimed to compare the efficacy and safety of finerenone versus spironolactone or eplerenone in patients with chronic heart failure. Methods: Electronic databases including MEDLINE, EMBASE, and CENTRAL were searched from inception to December 2017 for randomized controlled trials assessing finerenone treatment in patients with chronic heart failure. Data concerning the study’s design, patients’ characteristics, and outcomes were extracted. Risk ratio (RR) and mean differences (MD) were calculated using either fixed or random effects models. Results: Three trials with 1520 CHF patients were included in the systematic review. In terms of anti-ventricular remodeling, we calculated the effective number of cases with a 30% reduction in NT-proBNP. Finerenone was equivalent to the existing steroidal mineralocorticoid antagonist (P<.05). However, the efficacy of finerenone appeared to be dose-dependent. At a dose of 10mg/d finerenone was found to be marginally better than that of steroidal mineralocorticoid receptor antagonists (MRAs) (RR =1.18, 95% confidence interval [CI] 0.88, 1.57, P>.05). The incidence of treatment-related adverse events (TEAEs) of finerenone at 10mg/d was significantly lower than 25 to 50mg/d of steroidal MRAs (RR =0.81, 95% CI=0.66–0.99, P=.04).
    [Show full text]
  • Interactions with HBV Treatment
    www.hep-druginteractions.org Interactions with HBV Treatment Charts revised September 2021. Full information available at www.hep-druginteractions.org Page 1 of 6 Please note that if a drug is not listed it cannot automatically be assumed it is safe to coadminister. ADV, Adefovir; ETV, Entecavir; LAM, Lamivudine; PEG IFN, Peginterferon; RBV, Ribavirin; TBV, Telbivudine; TAF, Tenofovir alafenamide; TDF, Tenofovir-DF. ADV ETV LAM PEG PEG RBV TBV TAF TDF ADV ETV LAM PEG PEG RBV TBV TAF TDF IFN IFN IFN IFN alfa-2a alfa-2b alfa-2a alfa-2b Anaesthetics & Muscle Relaxants Antibacterials (continued) Bupivacaine ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Cloxacillin ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Cisatracurium ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Dapsone ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Isoflurane ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Delamanid ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Ketamine ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Ertapenem ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Nitrous oxide ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Erythromycin ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Propofol ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Ethambutol ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Thiopental ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Flucloxacillin ◆ ◆ ◆ ◆ ◆ ◆ Tizanidine ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Gentamicin ◆ ◆ ◆ ◆ ◆ ◆ Analgesics Imipenem ◆ ◆ ◆ ◆ ◆ ◆ ◆ Aceclofenac ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Isoniazid ◆ ◆ ◆ ◆ ◆ ◆ Alfentanil ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Levofloxacin ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Aspirin ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Linezolid ◆ ◆ ◆ ◆ ◆ ◆ Buprenorphine ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Lymecycline ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Celecoxib ◆ ◆ ◆ ◆ ◆ ◆ ◆ Meropenem ◆ ◆ ◆ ◆ ◆ ◆ Codeine ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ for distribution. for Methenamine ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Dexketoprofen ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Metronidazole ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Dextropropoxyphene ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ Moxifloxacin ◆ ◆ ◆
    [Show full text]
  • New Mesh Headings for 2019 Listed in Alphabetical Order with Heading, Scope Note, Annotation (AN), Previous Indexing (PI), and Tree Locations
    New MeSH Headings for 2019 Listed in alphabetical order with Heading, Scope Note, Annotation (AN), Previous Indexing (PI), and Tree Locations 17 alpha-Hydroxyprogesterone Caproate Hydroxyprogesterone derivative that acts as a PROGESTIN and is used to reduce the risk of recurrent MISCARRIAGE and of PREMATURE BIRTH. It is also used in combination with ESTROGEN in the management of MENSTRUATION DISORDERS. Tree locations: 17-alpha-Hydroxyprogesterone D04.210.500.745.745.654.829.395.400.500 D06.472.334.851.687.750.478.400.250 2-Methoxyestradiol A metabolite of estradiol that lacks estrogenic activity and inhibits TUBULIN polymerization. It has antineoplastic properties, including inhibition of angiogenesis and induction of APOPTOSIS. Tree locations: Estradiol D04.210.500.365.415.248.830 D06.472.334.851.437.500.750 5-Methoxypsoralen A linear furanocoumarin that has phototoxic and anti-inflammatory properties, with effects similar to METHOXSALEN. It is used in PUVA THERAPY for the treatment of PSORIASIS. Tree locations: Furocoumarins D03.383.663.283.446.794.688 D03.633.100.150.446.794.688 D03.633.300.770.688 Abciximab A Fab fragment of the chimeric monoclonal antibody 7E3 that binds to the glycoprotein IIb-IIIa receptor of human platelets, and blocks PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX, potently inhibiting PLATELET AGGREGATION. It is used in treatment of refractory unstable angina, and for prevention of ischemic complications in patients undergoing percutaneous coronary procedures such as ANGIOPLASTY; ATHERECTOMY; or stenting. Tree locations: Antibodies, Monoclonal, Humanized D12.776.124.486.485.114.224.060.125 D12.776.124.790.651.114.224.060.125 D12.776.377.715.548.114.224.200.125 Immunoglobulin Fab Fragments D12.644.541.500.650.125 D12.776.124.486.485.680.650.125 D12.776.124.790.651.680.650.125 D12.776.377.715.548.680.650.125 Acamprosate Structural analog of taurine that is used for the prevention of relapse in individuals with ALCOHOLISM.
    [Show full text]