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PubMed1984

[Hemodynamic study during 48 hours of delayed-release isosorbide dinitrate (repeated oral administration) in the acute phase of myocardial infarction complicated by left ventricular insufficiency].

The aim of this study was to evaluate the haemodynamic effects of slow release isosorbide dinitrate (IDN) 40 mg oral preparation over a 48 hour period in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (8 male, 6 female) were treated by repeat dose ISD (8 hourly) and the haemodynamic changes were recorded at 1 hr, 2 hrs, 6 hrs, 12 hrs, 24 hrs, and 48 hrs. After 48 hours treatment the heart rate was unchanged; mean arterial blood pressure fell from 109.5 +/- 5.6 mmHg to 93.5 +/- 6.2 mmHg (-15%) (p less than 0.01). Cardiac index rose from 2.4 +/- 0.57 1/min/m2 to 2.8 +/- 0.65 1/min/m2 (+16%) (NS); diastolic pulmonary artery pressure fell from 22.5 +/- 7.07 mmHg to 13.7 +/- 4.5 mmHg (-39%) (p less than 0.003); systolic pulmonary artery pressure fell from 40.5 +/- 12.2 mmHg to 28.6 +/- 11.6 mmHg (-30%) (NS). Systemic vascular resistance fell from 2 095.2 +/- 63 dynes/s/cm5 to 1 537 +/- 60 dynes/s/cm5 (-22.3%) (NS). Finally, total pulmonary resistance fell from 561.9 +/- 15 dynes/s/cm5 to 301.9 +/- 14.5 dynes/s/cm5 (-47%) (p less than 0.003). The most valuable effect was therefore the reduction in left ventricular filling pressures which was maximal after about 48 hours. Two groups of patients were identified according to the clinical outcome. The patients in Group I (11 cases) were improved by the fall in diastolic pulmonary artery pressure, the rise in cardiac index and the reduction of systemic valvular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Effects of nitric oxide donor, isosorbide dinitrate, on energy metabolism of rat reticulocytes.

Since nitric oxide (NO) in many cells is involved in energy metabolism, the aim of this study was to evaluate the role of isosorbide dinitrate (ISDN), a NO donor, in energy metabolism of rat reticulocytes, particularly due to their high content of hemoglobin--an effective scavenger of NO. Rat reticulocyte-rich red blood cell suspensions were aerobically incubated in the absence (control) or in the presence of different concentrations of ISDN. ISDN decreased total and coupled oxygen consumption (p<0.05) while increased uncoupled oxygen consumption (p<0.05) in a dose- and time-dependent manner. This was followed by enhancement of glycolysis, as measured by increased glucose consumption and lactate accumulation (p<0.05). Levels of all glycolytic intermediates in the presence of ISDN indicate only stimulation of pyruvate kinase activity. ISDN did not alter the concentration of ATP, while increased ADP and AMP levels (p>0.05). In rat reticulocytes under steady-state conditions, 95.4% of overall energy was produced by oxidative phosphorylation but only 4.6% by glycolysis. Due to a reduced coupled oxygen consumption in the presence of ISDN, ATP production via oxidative phosphorylation was significantly diminished. A simultaneous increase of glycolytic ATP production is not enough to ensure constant ATP production. The calculated mean ATP turnover time was prolonged by 199% in the presence of 1.5 mmol/l ISDN. In conclusion, ISDN a) inhibited total and coupled respiration but enhanced uncoupled respiration, b) stimulated glycolysis, c) decreased ATP production and d) prolonged ATP turnover time in rat reticulocytes. These effects were mediated by NO as the effector molecule.

Adenosine Diphosphate↗
PubMed1980

Radionuclide and hemodynamic assessment of left ventricular functional reserve in patients with left ventricular aneurysm and congestive cardiac failure. Response to exercise stress and isosorbide dinitrate.

The hemodynamic response to exercise stress was assessed in 17 patients with left ventricular (LV) aneurysm, demonstrated by contrast left ventriculography, and congestive cardiac failure (CCF) before and after sublingual isosorbide dinitrate (ISDN). Radionuclide ventriculography was performed at rest and during exercise in 14 patients. ISDN increased mean exercise LV stroke work index (LVSWI) from 31 to 39 g-m/m2 (p less than 0.001) and reduced mean exercise LV filling pressure from 38 to 25 mm Hg (p less than 0.001). Using the combined criteria of LVSWI and ejection fraction of the contractile section of the left ventricle (EFCS), no patient with rest EFCS of less than 40% achieved a good absolute response to exercise in LV performance with or without ISDN. Of the six patients with rest EFCS greater than or equal to 40% only three achieved a good response. While rest EFCS less than 40% indicates poor LV functional reserve, good LV functional reserve is not always indicated by rest EFCS greater than or equal to 40%.

Adult↗
PubMed1980

[Fendiline and isosorbide dinitrate in coronary heart disease (author's transl)].

In a randomized cross-over double-blind study of 30 out-patients with true angina the efficacy of fendiline and isosorbide dinitrate (ISDN) was compared. In randomized order the patients daily took either 3 X 50 mg fendiline or 2 X 20 mg ISDN (plus 1 placebo tablet). Each treatment period lasted for six weeks. Ergometric tests were performed at the onset of the study and at intervals of three weeks. The main criterion for the efficacy of the treatment was a change in S-T segment (at 0.06 s after the QRS). With either drug there occurred a statistically significant reduction in S-T depression and in the frequency of anginal attacks during the first treatment period. But there was a difference between the two drugs: Whereas with ISDN a marked reduction in S-T segment depression was observed after three weeks, this effect slightly receded in the second part of the treatment period, while with fendiline the reduction in S-T depression continued over the entire treatment period. There was no significant difference between the two drugs as to side-effects or tolerance.

Adult↗
PubMed1984

Nitrate cross-tolerance: effect of sublingual isosorbide dinitrate and nitroglycerin during sustained nitrate therapy.

In a randomized, single-blind, crossover study, 10 patients with stable, exercise-induced angina pectoris were studied during sustained therapy with oral isosorbide dinitrate (ISDN). Circulatory changes and exercise performance were evaluated before and 6 hours after therapy with oral ISDN. One-half hour after this therapy, sublingual ISDN or nitroglycerin (NTG) was administered and exercise testing repeated. Treadmill walking time 6 hours after oral ISDN was similar to the control value. Subsequent administration of sublingual ISDN improved walking time from 429 +/- 156 to 513 +/- 166 seconds (p less than 0.005), whereas after NTG improved from 411 +/- 159 to 480 +/- 158 second (p less than 0.005). The improvement in walking time with ISDN (23%) and NTG (18%) and the absolute walking times were not different. The standing systolic blood pressure decreased from 124 +/- 23 to 112 +/- 22 mm Hg (p less than 0.02) after therapy with sublingual ISDN and 122 +/- 23 to 110 +/- 24 mm Hg (p less than 0.005) after administration of NTG. This study demonstrates that (1) during sustained ISDN therapy, walking time returns to control values by 6 hours; (2) administration of either sublingual ISDN or NTG results in significant circulatory changes and improvement in walking time; and (3) the changes in circulatory and exercise variables after administration of NTG in patients taking sustained ISDN therapy cannot be taken as evidence of an absence of cross-tolerance between these agents.

Aged↗
PubMed1986

[Hemodynamic and anti-angina effects of transdermal nitroglycerin after acute and chronic administration. Additive effect of sublingual isosorbide dinitrate].

To evaluate the acute and chronic anti-anginal efficacy of a Transdermal Therapeutic System, releasing 10 mg of nitroglycerin over 24 hours (TTS 10), and possible additional effects of isosorbide dinitrate 5 mg (ISDN) sublingually (s.l.), ten patients with stable exercise-induced angina pectoris and pathological coronary angiography were studied. The protocol of the trial consisted of an initial acute study, carried out in double-blind conditions and following a cross-over design, to compare TTS 10 and placebo. Cycloergometric exercise tests were performed on the first and second day, 3 hours after dosing. After a 30 minute rest period, a sublingual 5 mg dose of ISDN was given and 15 minutes later a further exercise test was carried out. Subsequently, patients received TTS 10 in single-blind conditions for 16 days. On the 15th and 16th day, stress test was repeated, 3 hours after the application of active plasters and, 30 minutes later, a further exercise test was performed, 15 minutes after a sublingual dose of ISDN 5 mg or placebo, given in double-blind conditions and in randomized sequence. After acute and chronic administration, TTS 10 significantly improved exercise tolerance in comparison with placebo. During the first acute study, ISDN 5 mg s.l., led to a significant reduction in systolic BP, a reflex increase in heart rate and a further improvement in exercise tolerance, whether patients were on placebo or TTS.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Enhancement of the efficacy of isosorbide dinitrate by captopril in stable angina pectoris.

This study was designed to assess whether the angiotensin-converting enzyme inhibitor captopril could potentiate the efficacy of a single dose of oral isosorbide dinitrate (ISDN) in patients with coronary artery disease. Fourteen men (mean age 53 years) with stable angina pectoris were studied. In each patient the efficacy of placebo, captopril (50 to 100 mg), ISDN (10 mg), and a combination of captopril (50 to 100 mg) and ISDN (10 mg) was assessed by repeated exercise treadmill tests performed before and 1, 2, 3 and 6 hours after administration of a single dose. A single-blind, randomized technique was applied. According to the mean data in the whole group of 14 patients, captopril alone produced no improvement in exercise duration to the onset of angina and to angina of moderate severity compared with placebo. The magnitude of ST-segment depression did not significantly change after captopril administration. ISDN alone significantly increased exercise duration to onset of angina and to angina of moderate severity (antianginal effect) and decreased the magnitude of ST-segment depression (antiischemic effect) 1 to 3 hours after administration. Combined administration of ISDN and captopril resulted in more expressed antianginal and antiischemic effects; at 2, 3 and 6 hours these effects with ISDN plus captopril were significantly more pronounced than those with ISDN alone. According to individual data, the most marked potentiation of ISDN efficacy was observed in patients who had poor response to ISDN alone. In all 6 patients in whom ISDN alone was ineffective, after the addition of captopril the desired antianginal effect was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1994

Release of isosorbide dinitrate from polymer film dosage forms and absorption of this drug through the oral mucosa of rats.

In vitro release tests and in vivo absorption measurements of oral cavity dosage forms of isosorbide dinitrate (ISDN) prepared from mixed polymer film systems were conducted. Hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose phthalate (HPMCP) were used to make the films, and the tests were conducted with films made from various ratios of these two polymers. The effects of the addition of the accelerator glycyrrhizic acid (GL), on dissolution and absorption were also examined. The mean dissolution time (MDT) in the in vitro dissolution tests varied with the nature of the polymers and drug, as well as with the pH of the testing solution. The MDT for the polymer film system with GL was smaller than that without GL. In the in vivo absorption tests using rats, the absorption of ISDN through the oral mucosa was observed in all the systems. In the mixed polymer film systems, the mean residence time (MRT) increased with increasing the ratio of HPMCP/HPC. The values of the area under the curve (AUC) for the systems with GL was larger than for those without GL. A good correlation was demonstrated between the absorption rate constant, ka and the dissolution rate constant, kd.

Absorption↗
PubMed1989

Biotransformation of glyceryl trinitrate and isosorbide dinitrate in vascular smooth muscle made tolerant to organic nitrates.

It has been proposed that organic nitrates are prodrugs and biotransformation to a pharmacologically active metabolite (i.e., nitric oxide) must occur before the onset of vasodilation. If this postulated mechanism is correct, tolerance to organic nitrate-induced vasodilation might involve decreased biotransformation of organic nitrates by vascular smooth muscle. In this study, biotransformation of isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN) was estimated by measuring isosorbide mononitrate (ISMN) and glyceryl dinitrate (GDN), respectively, rather than the nitrate anion, because of a more sensitive method for measurement of ISMN and GDN. To test this hypothesis, isolated rabbit aortic strips (RAS) were made tolerant in vitro by incubation with 500 microM GTN or ISDN for 1 h. After a washout period and submaximal contraction with phenylephrine, the tissues were incubated with either 2.0 microM [14C]ISDN or 0.5 microM [14C]GTN for 2 min. ISDN- or GTN-induced relaxation of RAS was monitored and tissue parent drug and metabolite contents were determined by thin-layer chromatography and liquid scintillation spectrometry. ISDN- and GTN-induced relaxation of RAS and the metabolite concentrations were significantly less for both GTN- and ISDN-tolerant tissue compared with nontolerant tissue. These results are consistent with the hypothesis that organic nitrate biotransformation is required for organic nitrate-induced vasodilation.

Animals↗
PubMed1984

Effects of sublingual isosorbide dinitrate on left ventricular performance during exercise in patients with myocardial infarction.

In order to investigate left ventricular performance during exercise in patients with myocardial infarction and evaluate the effects of sublingual isosorbide dinitrate (ISDN) on left ventricular performance, we performed a symptom-limited multigraded exercise test using a bicycle ergometer in supine position. Thirty-seven patients with myocardial infarction were evaluated in order to clarify the hemodynamic responses to exercise with and without sublingual ISDN. Patients were subdivided into 3 groups according to the level of pulmonary capillary pressure (PCP) and cardiac index (CI) at peak exercise as follows: Group I (14 patients); PCP less than 18 mmHg, CI greater than or equal to 5.0 or CI less than 5.0 L/min/m2, Group II (11 patients); PCP greater than or equal to 18 mmHg, CI greater than or equal to 5.0 L/min/m2, Group III (12 patients); PCP greater than or equal to 18 mmHg, CI less than 5.0 L/min/m2. Exercise capacity without ISDN (control study) was correlated with left ventricular performance during exercise. Although left ventricular performance in patients who complained of dyspnea or chest pain at peak exercise was worse than those who complained of leg fatigue, we could not predict hemodynamics during exercise from the level of hemodynamic parameters at rest in each patient. Determinant factors of left ventricular performance during exercise were age, previous history of myocardial infarction, the severity of coronary artery lesion and the extent of left ventricular wall motion abnormality which was estimated by left ventriculogram as an index of infarct size. After sublingual ISDN (ISDN study), exercise capacity was improved. No patient terminated exercise because of chest pain and only one did because of dyspnea.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

[Effect of the vasodilator isosorbide dinitrate on ocular circulation].

BACKGROUND: Vasodilator drugs are increasingly being discussed as possible antiglaucomatous substances. Aim of the present study is to evaluate, from a hemodynamic point of view, the vasodilator drug isosorbide dinitrate (ISDN) regarding its suitability for glaucoma therapy. METHODS: 20 healthy subjects (mean age: 28 yrs) volunteered to participate in the study. In randomized order, each subject received one tablet containing 40 mg ISDN (sequels) or--in a second trial--one tablet placebo (+500 mg of the analgetic metamizol, respectively, for prophylaxis of nitrate headache). 1 h before as well as 1, 3, 5, and 7 hrs after medication, the following variables were determined using oculo-oscillo-dynamography: systolic ophthalmic artery pressure (SOAP), systolic ocular perfusion pressure (SOPP), ocular pulsation amplitude (OPA) and the product OPA x heart rate (HR). Intraocular pressure (IOP) as well as systolic and diastolic brachial artery pressures (SBAP, DBAP) were also measured. RESULTS: After administration of ISDN (+analgetic), the variables SBAP, SOAP and SOPP were significantly (p = 0.01) lowered compared to placebo (+analgetic), and also the IOP tended to be lower (p = 0.08). The maximum reduction was found 3-5 hrs after medication: SBAP 10.9 mm Hg (9%), SOAP 12.5 mm Hg (14%), SOPP 11.3 mm Hg (14.5%), and IOP 1.5 mm Hg (12%). The relation SOAP vs. SBAP was significantly (p = 0.0004) linear, the correlation coefficient amounted to 0.39. DBAP remained unchanged, HR was increased by 4-7 beats/min (p = 0.08). OPA and the product OPA x HR showed highly significant decreases by maximum values of 44% and 40%, respectively. CONCLUSION: ISDN (+analgetic) caused a reduction of SOAP and SOPP, which can be accounted for by the reduced systolic systemic blood pressure. In addition, there was a decrease of OPA and of the product OPA x HR (a measure of pulsatile ocular blood flow), which finding may be explained by a cardiac stroke volume reduction that is typical for nitrates. Due to these hemodynamic effects and due to the only weak IOP reduction, ISDN does not appear to be suitable for glaucoma therapy.

Adult↗
PubMed1979

Effects of isosorbide dinitrate on pulmonary hypertension in chronic obstructive pulmonary disease.

Eighteen patients with chronic obstructive pulmonary disease with pulmonary hypertension were studied to assess the hemodynamic response to acute oxygen administration and to oral isosorbide dinitrate (ISDN). All 18 patients had baseline hemodynamic measurements and hemodynamic measurements during low-flow nasal oxygen. Following a second baseline measurement, patients received either oral ISDN (11 patients) or placebo (7 patients) in a randomized, double-blind protocol. Heart rate decreased with oxygen administration but there were no other significant hemodynamic changes. With oral ISDN, there was a significant fall in pulmonary artery and brachial artery pressure. Cardiac output, right atrial pressure, pulmonary wedge pressure, and pulmonary vascular resistance all fell but not significantly. We conclude that oral ISDN is effective in reducing pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Blood Pressure↗
PubMed1988

More rapid relief of pain with isosorbide dinitrate oral spray than with sublingual tablets in elderly patients with angina pectoris.

To evaluate the possibility of improving clinical practice in the treatment of angina pectoris, the duration of relief of pain with isosorbide dinitrate (ISDN) oral spray and sublingual tablets were compared in elderly patients with chronic stable angina pectoris. Nine patients (mean age 67 years) were studied in a randomized crossover trial. The patients underwent bicycle ergometry, which resulted in typical chest pain associated with electrocardiographic ST-segment depression in all 9. The patients received ISDN oral spray or sublingual tablets immediately on termination of exercise. At least 6 hours later another ergometry test was performed and the patients were crossed over to the other drug. ISDN spray relieved pain in all patients at a mean duration of 61.6 +/- 24.4 seconds after administration, whereas the duration of relief of pain by ISDN sublingual tablets was 112.4 +/- 70 seconds. The difference was highly significant (p less than 0.0005). It is concluded that clinical practice of treatment of angina pectoris in the elderly can be improved by using ISDN oral spray rather than sublingual tablets. The spray is effective at twice the rapidity of the sublingual tablet.

Administration, Oral↗
PubMed1977

[Effect of sublingual isosorbide dinitrate on hemodynamics in coronary patients with and without congestive heart failure (author's transl)].

In 17 patients with coronary heart disease, hemodynamic measurements were performed before and after sublingual application of 10 mg isosorbide dinitrate (ISDN). 10 patients showed signs of heart failure with pulmonary congestion and a left ventricular filling pressure above 15 mmHg, resting hemodynamics were normal in 7 patients. Eight of the patients with left ventricular failure had sustained acute myocardial infarctions the size of which was assessed by serial determinations of serum creatine phosphokinase. Application of ISDN resulted in a significant decrease of systemic and pulmonary artery pressures and pulmonary capillary wedge and right atrial pressures of patients both with and without left ventricular failure. Cardiac index and stroke index as well as systemic and pulmonary resistances did not change significantly. ISDN did not affect left ventricular stroke work in patients with elevated filling pressures; however, a decrease of normal filling pressures was associated with a decrease of stroke work. Thus, in coronary patients with chronic congestive heart failure, sublingual application of nitrates results in a beneficial hemodynamic unloading. However, if the acute infarct size is taken into account, it can be demonstrated that hemodynamic improvement after ISDN--judged by the relation stroke work/filling pressure--becomes less pronounced with increasing infarct size.

Adult↗
PubMed2004

Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction.

OBJECTIVE: To compare the effects of nicorandil (a hybrid ATP sensitive potassium channel (K+(ATP) channel) opener/nitric oxide donor) with those of isosorbide dinitrate (ISDN) on myocardial microcirculation and cardiac function in patients with acute myocardial infarction (AMI) who had undergone reperfusion treatment by direct balloon angioplasty. DESIGN: Double blind randomised study. PATIENTS: 60 patients with AMI in Killip class I. INTERVENTIONS: Patients were assigned into two treatment groups: a nicorandil group (n = 30) and an ISDN group (n = 30). Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission and was administered directly to the treated coronary artery immediately after angioplasty. RESULTS: Compared with ISDN, nicorandil more frequently caused recovery of ST segment elevation just after reperfusion (15 of 27 (55.5%) in the nicorandil group v 5 of 26 (19.2%) in the ISDN group, p = 0.006). The nicorandil group had higher values of averaged peak velocity 40 minutes after reperfusion (mean (SD) 24.8 (13.3) cm/s v 16.0 (11.1) cm/s, p = 0.045) and higher values of regional wall motion of the infarcted area three weeks after onset of AMI (-1.78 (1.11) v -2.50 (1.04) SD/chord, p = 0.046). CONCLUSIONS: A combination of nicorandil drip infusion starting before reperfusion and intracoronary injection immediately after reperfusion is more effective than a similarly performed infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI area. The nicorandil regimen resulted in better left ventricular regional wall motion.

Angioplasty, Balloon↗
PubMed1993

Influence of isosorbide dinitrate (ISDN) on compliance of the pulmonary venous system.

Irreversible poor pulmonary venous compliance can worsen the natural course of patients with high pulmonary capillary wedge pressure, especially those with mitral stenosis, but nitrates (isosorbide dinitrate--ISDN), which have venodilatory properties, could increase this compliance in most patients. The aim of this study was to assess the hemodynamic effects of ISDN in patients with mitral stenosis, with special emphasis on the pulmonary venous compliance. Pulmonary venous compliance was estimated according to the Hirakawa equation (dV/dp = 0.4 x k2 x sV/(v-d)) in 39 patients with mitral stenosis during preoperative right heart catheterization with Vygon 5155-180 thermodilution catheters at rest and during exercise (25 W) in the supine position. This procedure was repeated after the application of 3.75 mg of Iso-Mack spray. Overall, ISDN increased pulmonary venous compliance significantly both at rest and during exercise (6.0 to 7.5 ml/mmHg and 6.0 to 7.6 ml/mmHg, respectively). The patients were divided into two groups according to their level of ISDN response; those with a good response of an increase of 15% or more in pulmonary venous compliance (Group I), and those with an increase of less than 15% (Group II). There were significant differences between these two groups in stroke volume index and heart rate. In Group I, while the mean right atrial pressure, mean pulmonary artery pressure and mean pulmonary wedge pressure all decreased significantly, there was a simultaneous insignificant decrease in the stroke volume index and an also insignificant increase in the heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function, Right↗
PubMedDate not supplied

Nisoldipine versus isosorbide dinitrate in coronary heart disease: results of a double-masked study.

The efficacy and tolerability of a twice-daily dose of 5 mg of nisoldipine versus 40 mg of sustained-release isosorbide dinitrate (ISDN) were compared in a randomized, double-masked study in 91 patients. During the 21-day treatment period, the mean time taken during bicycle ergometry to the appearance of an ST segment depression of at least 0.1 mV compared with the resting value increased from 287 +/- 129 seconds to 391 +/- 150 seconds in the nisoldipine group and from 254 +/- 140 seconds to 350 +/- 191 seconds in the ISDN group. The mean value at the end of treatment calculated by using analysis of covariance was 383 seconds in both groups. The difference between the two treatment groups was not statistically significant. The mean ST segment depression at individually maximal workload decreased from 0.19 +/- 0.07 mV to 0.12 +/- 0.08 mV in the nisoldipine group and from 0.18 +/- 0.07 mV to 0.14 +/- 0.08 mV in the ISDN group. The mean total duration of exercise increased from 420 +/- 161 seconds to 497 +/- 140 seconds in the nisoldipine group and from 425 +/- 167 seconds to 456 +/- 168 seconds in the ISDN group. In the nisoldipine group, 9 patients reported 12 adverse events that were considered to be possibly or probably related to the test medication; in the ISDN group, 13 patients reported 26 adverse events. Although the anti-ischemic effect of the two treatments was comparable, nisoldipine was descriptively superior to ISDN in terms of tolerability.

Aged↗
PubMedDate not supplied

BiDil (isosorbide dinitrate and hydralazine): a new fixed-dose combination of two older medications for the treatment of heart failure in black patients.

BiDil is a new fixed-dose combination of 2 older medications, isosorbide dinitrate (ISDN) and hydralazine. ISDN is an organic nitrate that is biotransformed into nitric oxide, a potent vasodilator. Hydralazine is believed to have both vasodilatory properties specific to the arteries and antioxidant properties, which address both the biochemical alterations in the failing cardiovascular system as well as the issue of nitrate tolerance. A drug regimen combining an NO stimulator (ISDN) with an antioxidant (hydralazine) favorably influences the nitroso-redox balance. Retrospective analyses of previous heart failure (HF) clinical trials comparing the combination of ISDN and hydralazine with placebo and enalapril, respectively, demonstrated a benefit in the black population, setting the precedent for a race-based therapeutic study, the African-American Heart Failure Trial (A-HeFT). A-HeFT examined the use of BiDil added to standard HF therapy in blacks with New York Heart Association functional class III and IV HF. BiDil demonstrated a 43% reduction in mortality when compared with placebo. As a result, current evidence-based treatment guidelines recommend that the addition of ISDN and hydralazine in black patients with moderate to severe HF optimized on standard therapy be considered. BiDil is currently indicated for the treatment of HF as an adjunct to standard therapy in black patients. The use of BiDil for black patients with mild disease or in nonblack patients with HF has not been studied. Future clinical trials involving an ethnically and clinically diverse population of patients would further define the role of combined ISDN and hydralazine in the treatment of HF.

Black People↗