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The New England Journal of Medicine Nov 2004We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy.
METHODS
A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life.
RESULTS
The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1+/-1.9 vs. -0.5+/-2.0, P=0.01; range of possible values, -6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6+/-20.6 vs. -2.7+/-21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]).
CONCLUSIONS
The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.
Topics: Adult; Aged; Black People; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Nitric Oxide Donors; Quality of Life; Survival Analysis; Treatment Outcome; Vasodilator Agents
PubMed: 15533851
DOI: 10.1056/NEJMoa042934 -
PLoS Neglected Tropical Diseases Sep 2018Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders, including megaesophagus. Treatment focuses on improving symptoms, and isosorbide and nifedipine may be used for this purpose.
METHODOLOGY
We conducted a systematic review to evaluate the effectiveness of pharmacological treatment for Chagas' megaesophagus. We searched MEDLINE, Embase and LILACS databases up to January 2018. We included both observational studies and RCTs evaluating the effects of isosorbide or nifedipine in adult patients with Chagas' megaesophagus. Two reviewers screened titles and abstracts, selected eligible studies and extracted data. We assessed the risk of bias using NIH 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group' and RoB 2.0 tool. Overall quality of evidence was assessed using GRADE.
PRINCIPAL FINDINGS
We included eight studies (four crossover RCTs, four before-after studies). Three studies evaluated the effect of isosorbide on lower esophageal sphincter pressure (LESP), showing a significant reduction (mean difference -10.52mmHg, 95%CI -13.57 to-7.47, very low quality of evidence). Three studies reported the effect of isosorbide on esophageal emptying, showing a decrease in esophageal retention rates (mean difference -22.16%, 95%CI -29.94 to -14.38, low quality of evidence). In one study, patients on isosorbide reported improvement in the frequency and severity of dysphagia (moderate quality of evidence). Studies evaluating nifedipine observed a decrease in LESP but no effect on esophageal emptying (very low and low quality of evidence, respectively). Isosorbide had a higher incidence of headache as a side effect than nifedipine.
CONCLUSIONS
Although limited, available evidence shows that both isosorbide and nifedipine are effective in reducing esophageal symptoms. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile.
TRIAL REGISTRATION
PROSPERO CRD42017055143. ClinicalTrials.gov CRD42017055143.
Topics: Adolescent; Adult; Aged; Chagas Disease; Esophageal Achalasia; Female; Humans; Isosorbide; Male; Middle Aged; Nifedipine; Treatment Outcome; Young Adult
PubMed: 30265663
DOI: 10.1371/journal.pntd.0006836 -
American Family Physician Aug 2016Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects... (Review)
Review
Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.
Topics: Administration, Topical; Amines; Amitriptyline; Analgesics; Analgesics, Opioid; Anesthetics, Local; Capsaicin; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; Humans; Isosorbide Dinitrate; Lidocaine; Phenols; Pregabalin; Sensory System Agents; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Tapentadol; Tramadol; Transcutaneous Electric Nerve Stimulation; Vasodilator Agents; Venlafaxine Hydrochloride; gamma-Aminobutyric Acid
PubMed: 27479625
DOI: No ID Found -
Journal of Comparative Effectiveness... Apr 2020The cost-effectiveness of isosorbide-5-mononitrate (5-ISMN) and isosorbide dinitrate (ISDN) in real-world use in patients with coronary heart disease (CHD; either... (Comparative Study)
Comparative Study
The cost-effectiveness of isosorbide-5-mononitrate (5-ISMN) and isosorbide dinitrate (ISDN) in real-world use in patients with coronary heart disease (CHD; either angina pectoris or myocardial infarction) was retrospectively compared. In this retrospective real-world evaluation, patients with established CHD satisfying the following criteria were selected from information system of two tertiary hospitals in China: with pharmacy claiming for at least one injection of 5-ISMN or ISDN between July 2008 and May 2017; and, CHD patients. By using propensity score matching (PSM), we compared clinical aspects of efficacy, safety, length of hospital stay and cost during hospitalization between 5-ISMN and ISDN group. All data were processed by R statistical package v.2.13.1 (R Foundation for Statistical Computing, Vienna, Austria). Of 5609 patients selected, 4047 received 5-ISMN and 1562 received ISDN. After PSM, we acquired 1555 pairs based on balancing of age, sex, insurance and comorbidities on admission. The frequency (4.2 ± 6.6-times vs 6.5 ± 9.5-times; p < 0.05) and total dosage (47.5 ± 153.4 vs 136.4 ± 261.0 mg; p < 0.05) of sublingual nitroglycerin use decreased and hypotension incidence lowered (8.0 vs 13.0%; p < 0.05) in 5-ISMN group compared with ISDN group. Hospital stay (16.0 ± 11.3 days vs 17.7 ± 13.2; p < 0.05) and hospitalization expenditure ([the ratio of cost in the study to the average hospitalization cost in the city] [odds ratio: 2.5 vs 2.6; p < 0.05]) were reduced in 5-ISMN group as with that of ISDN group. Moreover, the main component of hospitalization cost was medical consumables and medications in both the groups. In the present retrospective real-world evaluation, by using PSM analysis, we found that newer injection agent of 5-ISMN was associated with fewer use of sublingual nitroglycerin, less hypotension incidence, shorter length of hospital stay and less hospitalization expenditure related to its comparator ISDN in patients with established CHD. Further evaluation and clinical experience are need in different circumference for the usage of ISDN.
Topics: Administration, Sublingual; Aged; Aged, 80 and over; China; Coronary Disease; Cost-Benefit Analysis; Female; Health Care Costs; Humans; Hypotension; Incidence; Isosorbide; Isosorbide Dinitrate; Length of Stay; Male; Middle Aged; Nitric Oxide Donors; Nitroglycerin; Pragmatic Clinical Trials as Topic; Propensity Score; Retrospective Studies; Vasodilator Agents
PubMed: 32301331
DOI: 10.2217/cer-2019-0099 -
JACC. Heart Failure Sep 2017
Topics: Black or African American; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Treatment Outcome
PubMed: 28711448
DOI: 10.1016/j.jchf.2017.05.005 -
Stroke Jan 2022Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke.
METHODS
Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication.
RESULTS
Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (β=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (β=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (β=0.021%/mm Hg [95% CI, 0.005-0.037]).
CONCLUSIONS
While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.
Topics: Aged; Cerebral Small Vessel Diseases; Cilostazol; Female; Hemodynamics; Humans; Isosorbide Dinitrate; Lipoproteins; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome; Vasodilator Agents
PubMed: 34847709
DOI: 10.1161/STROKEAHA.121.034866 -
British Medical Journal Sep 1978
Topics: Adrenergic beta-Antagonists; Angina Pectoris; Humans; Isosorbide Dinitrate; Nifedipine; Nitroglycerin; Perhexiline
PubMed: 30515
DOI: 10.1136/bmj.2.6142.939 -
Polymers Apr 2023Thermoplastic starch (TPS) has emerged as an essential alternative to produce environmentally friendly packaging; however, retrogradation is a disadvantage that affects...
Thermoplastic starch (TPS) has emerged as an essential alternative to produce environmentally friendly packaging; however, retrogradation is a disadvantage that affects its shelf life. This study analyzed the co-plasticizing effect of isosorbide on the mechanical, thermal, physicochemical, and microstructural properties and the retrogradation of films obtained by blown film extrusion from thermoplasticized starch with mixtures of glycerol and isosorbide in different ratios (3:0, 2:1, 1:2, and 0:3, respectively). The results showed that the higher concentration of isosorbide significantly increased the tensile strength; however, it reduced the elongation. Retrogradation modeled using the Avrami equation showed that the presence of isosorbide reduced the retrogradation rate (k) and modified the recrystallization mechanism (n). The relative crystallinity in the plasticized TPS films was reduced to 89%, and the adsorption significantly decreased. Isosorbide was very important in reducing the retrogradation of TPS. The best performance was obtained with the 2:1 ratio of glycerol/isosorbide due to the synergistic effect between the plasticizers. The results would allow tuning the properties of TPS films by combining glycerol/isosorbide in different ratios, which enables the design of materials tailored to potential application requirements.
PubMed: 37177247
DOI: 10.3390/polym15092104 -
ESC Heart Failure Jun 2019Population data indicate that one in 25 persons of African ancestry has heart failure, a condition with relatively high mortality of around 50% in 5 years. Combined...
AIMS
Population data indicate that one in 25 persons of African ancestry has heart failure, a condition with relatively high mortality of around 50% in 5 years. Combined hydralazine and isosorbide dinitrate added to conventional therapy in African ancestry patients with heart failure and reduced ejection fraction improves quality of life and reduces the rate of first hospitalization for heart failure by 33% and annual mortality by 43%. The objectives of this study were to quantify the use of this guideline-recommended therapy in Europe and the potential effect of implementation gaps on mortality.
METHODS AND RESULTS
Prescription drug registration and utilization databases and population statistics were analysed in a cross-European survey without language restriction. Main outcomes were the number of unique patients prescribed the fixed combination hydralazine-isosorbide dinitrate (primary) or both drugs (secondary) in Europe in 2015, and the excess mortality related to prescribing practices was estimated. The survey indicates that around 12 million persons of African ancestry live in Europe. It is estimated that 480 000 persons of this population group have heart failure, with 120 000 eligible for hydralazine and isosorbide dinitrate therapy. However, single-pill hydralazine-isosorbide dinitrate is not authorized and therefore not dispensed in Europe in 2015. Out of the 25 European nations surveyed, the UK and the Netherlands are the only countries with major African ancestry populations where both hydralazine and isosorbide dinitrate are available for oral use, aside Norway, Sweden, and Finland. Hydralazine and isosorbide dinitrate are prescribed to <500 European patients in 2015. Thus, despite the recommendations of the European Society of Cardiology, the large majority of African-European patients with heart failure do not receive this drug combination, potentially resulting in 4800 to 5800 excess deaths yearly.
CONCLUSIONS
The life-saving, guideline-recommended, adjunctive therapy for heart failure in African ancestry patients with hydralazine and isosorbide dinitrate is rarely used in Europe. This major evidence-practice gap should urgently be overcome to reduce excess mortality in African-European patients with heart failure.
Topics: Black People; Cardiovascular Agents; Cross-Sectional Studies; Databases, Pharmaceutical; Drug Combinations; Drug Prescriptions; Europe; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate
PubMed: 30892835
DOI: 10.1002/ehf2.12421 -
Journal of Nanobiotechnology Nov 2022Ovarian cancer is a highly fatal gynecologic malignancy worldwide. Chemotherapy remains the primary modality both for primary and maintenance treatments of ovarian...
Ovarian cancer is a highly fatal gynecologic malignancy worldwide. Chemotherapy remains the primary modality both for primary and maintenance treatments of ovarian cancer. However, the progress in developing chemotherapeutic agents for ovarian cancer has been slow in the past 20 years. Thus, new and effective chemotherapeutic drugs are urgently needed for ovarian cancer treatment. A reduction-responsive synergetic delivery strategy (PSSP@ART-ISMN) with co-delivery of artesunate and isosorbide 5-mononitrate was investigated in this research study. PSSP@ART-ISMN had various effects on tumor cells, such as (i) inducing the production of reactive oxygen species (ROS), which contributes to mitochondrial damage; (ii) providing nitric oxide and ROS for the tumor cells, which further react to generate highly toxic reactive nitrogen species (RNS) and cause DNA damage; and (iii) arresting cell cycle at the G0/G1 phase and inducing apoptosis. PSSP@ART-ISMN also demonstrated excellent antitumor activity with good biocompatibility in vivo. Taken together, the results of this work provide a potential delivery strategy for chemotherapy in ovarian cancer.
Topics: Female; Humans; Artesunate; Reactive Oxygen Species; Polymers; Isosorbide Dinitrate; Ovarian Neoplasms; Nanoparticles
PubMed: 36335352
DOI: 10.1186/s12951-022-01676-3