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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 -
Pediatric Cardiology Apr 2023After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher...
After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.
PubMed: 37084132
DOI: 10.1007/s00246-023-03156-3 -
Annals of Hepato-biliary-pancreatic... Aug 2020Acute pancreatitis is the most widespread complication of endoscopic retrograde cholangiopancreatography. Here, we investigated the efficacy of rectal suppository...
BACKGROUNDS/AIMS
Acute pancreatitis is the most widespread complication of endoscopic retrograde cholangiopancreatography. Here, we investigated the efficacy of rectal suppository naproxen, sublingual isosorbide dinitrate and their co-administration in the prevention of post-ERCP pancreatitis.
METHODS
This double-blind randomized clinical trial carried out from June 2015 to February 2016 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 585 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients divided into three groups. Group A received 500 mg naproxen, group B took 5 mg isosorbide dinitrate, and group C was co-administrated both agents before ERCP. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and increase of serum amylase activity more than 3 times over the upper normal limit (60-100 IU/L) within first the 24 h post-ERCP.
RESULTS
Totally, 80 patients developed PEP included 29 (4.9%), 24 (4.1%), and 27 (4.6%) patients in groups A, B, and C, respectively (=0.845). Longer ERCP time (=0.041), using diazepam (=0.033), a higher number of pancreatic ducts cannulation (<0.001), pancreatic duct injection (=0.013), and using pancreatic stent (=0.004) were the predisposing factors for PEP.
CONCLUSIONS
Our findings indicated that prophylactic naproxen suppository or isosorbide dinitrate sublingually or co-administration had no significant difference in the prevention and severity of PEP, however, enhancing the endoscopist's skills can be effective. Departments and educational hospitals should develop their assessment and quality assurance measures for the training of fellows' not only technical training but also an understanding of the diagnostic and therapeutic roles of the procedure.
PubMed: 32843590
DOI: 10.14701/ahbps.2020.24.3.259 -
Kidney360 Dec 2020Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown.
METHODS
Single-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD/HY in maintenance HD. Participants were randomized to placebo or combination ISD/HY. Dose was escalated over 3 weeks from ISD 10 mg/HY 10 mg to ISD 40 mg/HY 75 mg three times per day with the maximum tolerated dose maintained for the subsequent 21 weeks. Primary endpoints included adverse events, adverse events precluding further treatment with study medication, serious hypotension (., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E' velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography.
RESULTS
A total of 17 individuals were randomized to ISD/HY (=7) or placebo (=10). All participants assigned to ISD/HY completed dose escalation to 40/75 mg, but dose reductions were required in two participants. No participants discontinued therapy. There were no serious hypotension events. Recurrent intradialytic hypotension was less frequent with ISD/HY (0.47 events/patient-year) than placebo (1.83 events/patient-year, =0.04). In contrast, nausea (ISD/HY, 1.90 events/patient-year; placebo, 0.50 events/patient-year, =0.03) was significantly more frequent, and headache and diarrhea were numerically but not significantly more frequent with ISD/HY. Adverse events were more frequent with ISD/HY (11.4 events/patient-year) than placebo (6.31 events/patient-year). We did not detect between-group differences in the change in E' (=0.34); ISD/HY showed a mean increase of 0.6 cm/s (SD 1.1), and placebo showed a mean decrease of 0.04 cm/s (SD 0.9). Changes in coronary flow reserve were minimal, -0.3 (0.2) with ISD/HY and -0.03 (0.5) in the placebo group, =0.19.
CONCLUSIONS
ISD/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD/HY compared with placebo.
Topics: Humans; Hydralazine; Isosorbide Dinitrate; Kidney Failure, Chronic; Pilot Projects; Renal Dialysis; Tomography, X-Ray Computed
PubMed: 35372900
DOI: 10.34067/KID.0004342020 -
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 -
RSC Advances Aug 2021Isosorbide dinitrate (ISD) and hydralazine hydrochloride (HDZ) are critical drugs for the treatment of heart failure. Currently, no available analytical method for the...
Isosorbide dinitrate (ISD) and hydralazine hydrochloride (HDZ) are critical drugs for the treatment of heart failure. Currently, no available analytical method for the determination of ISD and HDZ exists as per the literature that combines UPLC and Green Analytical Quality by Design, which is critical for designing a method that is sustainable for long-term use. This study proposes an eco-friendly determination of isosorbide dinitrate (ISD) and hydralazine hydrochloride (HDZ) using a Green Analytical Quality by Design-based UPLC Method. The developed technique is capable of separating ISD and HDZ, as well as their degradation products, using a Phenomenex C18 (50 × 2.1 mm, 2 μm) column containing ethanol and 0.1% trifluoroacetic acid (60 : 40% v/v) at a flow rate of 0.5 mL min. This technique was validated and established a linearity range of 10-60 μg mL and 18.75-112.5 μg mL, with of 0.9998 and 0.9992 for ISD and HDZ, respectively along with accuracy, reproducibility, and selectivity. The new approach was further evaluated using five different assessment techniques such as National Environmental Methods Index, Analytical Eco-Scale, Green Analytical Procedure Index, Analytical Method Greenness Score, and Analytical GREEnness Metrics, and was determined to be environmentally benign. Based on these results, we have concluded that the developed UPLC technique with the combined approach of Green Analytical Quality by Design for determining stability might benefit in the creation of novel pharmaceutical products such as isosorbide dinitrate and hydralazine.
PubMed: 35480770
DOI: 10.1039/d1ra04843k -
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 -
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 -
Diabetes & Vascular Disease Research Jul 2018To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot... (Comparative Study)
Comparative Study Randomized Controlled Trial
Efficacy and safety of the combination of isosorbide dinitrate spray and chitosan gel for the treatment of diabetic foot ulcers: A double-blind, randomized, clinical trial.
AIM
To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot ulcers.
METHODS
In a randomized, placebo-controlled, double-blinded clinical trial, 68 patients were divided into four groups: Group 1: treated with chitosan gel; Group 2: isosorbide dinitrate spray; Group 3: combination of isosorbide dinitrate spray and chitosan gel; Group 4: placebo.
RESULTS
Histological analyses showed a significant regeneration in all groups ( p < 0.001). On the final assessment of the ulcer, using the combination was found a wound closure percentage of 71 ± 30, 70 ± 27 using isosorbide dinitrate, 58 ± 30 with chitosan and 50 ± 16 with placebo. The number of patients who achieved complete ulcer closure was six using the combination, four with isosorbide dinitrate, three with chitosan and one with placebo. The progression in the healing process of the ulcer showed marked inmunohistochemical differences of Von Willebrand Factor, desmin, vascular endothelial growth factor-A and α-smooth muscle actin in all groups ( p < 0.001), but without notable differences between them.
CONCLUSION
The combination was better than placebo to reduce the dimensions of the ulcer, accelerate healing and increase the number of patients who achieved complete closure of the ulcer, but the combination was not better than chitosan or isosorbide dinitrate used separately.
Topics: Administration, Cutaneous; Aerosols; Bandages; Biomarkers; Chitosan; Diabetic Foot; Double-Blind Method; Drug Therapy, Combination; Female; Gels; Humans; Isosorbide Dinitrate; Male; Mexico; Skin; Time Factors; Treatment Outcome; Vasodilator Agents; Wound Healing
PubMed: 29682995
DOI: 10.1177/1479164118769528