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PubMed1984

Treatment of coronary heart disease with isosorbide mononitrate ('Elantan' 20): a multi-centre study in hospital and general practice.

An open, multi-centre clinical trial was carried out in 537 hospital patients and 2138 general practice patients to evaluate the efficacy and tolerance of isosorbide 5-mononitrate in the treatment of angina pectoris. Prior to entry into the trial, angina attack frequency and acute glyceryl trinitrate consumption were assessed during previous, in most cases unsatisfactory, anti-anginal therapy. After a treatment-free washout period of 3 days, graded multi-stage exercise testing was performed and then treatment started with 20 mg isosorbide mononitrate 3-times per day. Exercise testing was repeated after 14 days' therapy and, in the case of the hospital patients, also 4 to 5 hours after the first dose of isosorbide mononitrate. At the end of the 14-day treatment period, angina attack frequency and glyceryl trinitrate consumption were again assessed. Similar results were obtained for both hospital and general practice patients. Changing to isosorbide mononitrate resulted in a marked reduction in angina frequency, with complete elimination of angina attacks in approximately half of the patients; nocturnal angina, present in approximately 20% of the patients during previous therapy, virtually disappeared during isosorbide mononitrate therapy. Exercise tolerance and performance improved in the majority of patients, with a marked increase in the number of patients able to exercise to the level at which some symptom other than angina pectoris caused them to stop. ST-depression during exercise and exercise-induced arrhythmias also showed clear reductions during isosorbide mononitrate therapy. Tolerance to isosorbide mononitrate was good, the expected 'nitrate headaches' being the only common side-effect reported. The results were such that continuation of treatment with isosorbide mononitrate after the trial was recommended by the attending physician in 77% of the hospital patients and 87% of the general practice patients.

Adult↗

PubMed1976

Hemodynamic effects of isosorbide dinitrate vs nitroglycerin in patients with unstable angina.

The hemodynamic response to nitroglycerin administration, to sublingual or oral administration of isosorbide dinitrate, or to a placebo was evaluated and compared in 37 patients with unstable angina pectoris under resting, pain-free conditions. Patients with congestive heart failure were not included in this study. Serial measurements of mean arterial blood pressure (MAP), pulmonary arterial end-diastolic pressure (PAEDP), cardiac index (CI), and heart rate (HR) were obtained for one hour following nitroglycerin administration and for four hours following sublingual or oral administration of isosorbide dinitrate. Echocardiographic end-diastolic volume (EDV) measurements were obtained for the groups receiving isosorbide dinitrate or placebo. There was a significant (P less than 0.05 or less than 0.1) reduction of the MAP (5 to 10 mm Hg) that persisted for more than four hours following both sublingual and oral administration of isosorbide dinitrate. The changes in the PAEDP, HR, and CI following sublingual or oral administration of isosorbide dinitrate were small and not significant. In the group receiving isosorbide dinitrate sublingually, the EDV was reduced by more than 30 ml below the placebo group (P less than 0.1) for up to four hours. The effects of nitroglycerin administration were similar in magnitude but of much shorter duration (three to four hours for sublingual and oral administration of isosorbide dinitrate vs 15 to 30 minutes for nitroglycerin). These data demonstrate that the duration of the hemodynamic effects of sublingually and orally administered isosorbide dinitrate in patients with unstable angina pectoris and normal resting hemodynamics is 8 to 12 times longer than that of nitroglycerin.

Administration, Oral↗

PubMed2000

Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: a review. DUMQOL (DUtch Mononitrate Quality of Life) Study Group.

Since the first publication of isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation in 1985, a considerable body of literature concerning its clinical efficacy and safety has become available. Theoretically, the formulation has the advantage over conventional isosorbide mononitrate or dinitrate (ISMN/ISDN) that it has a simpler and more predictable pharmacokinetic profile. The objectives of this paper are to review published data so far and to see whether the theoretical advantages translate into better clinical effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a rapid onset of action (30 minutes), and effects are evident for up to 17 hours. 2. The antianginal effects of once-daily isosorbide mononitrate IR-SR increased with increasing dosages, were generally larger than those of either placebo or equipotent doses of conventional ISMN/ISDN, and were somewhat larger than those of the beta blocker bupranolol. The effects were generally similar to those of sustained release nifedipine. 3. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate IR-SR than with twice or three times daily regimens of conventional ISMN/ISDN. This was particularly so with mobility, psychological distress, and life satisfaction indices. 4. Tolerance did not develop after 13 months of once daily isosorbide dinitrate IR-SR. No rebound increase in incidence of ischemic episodes was observed after discontinuation of treatment. 5. Long-term efficacy data both of isosorbide mononitrate IR-SR and of conventional ISMN/ISDN are limited so far. Large studies in patients with angina pectoris and patients with heart failure addressing long-term effects are ongoing, and some of the data will be completed within the next months. Isosorbide mononitrate IR-SR has a rapid onset of action and has been shown to be clinically efficient and, in addition, to be more so than conventional ISMN / ISDN. Nitrate tolerance with continued use of the formulation has not yet been reported. Long-term effects on morbidity and mortality are currently being assessed.

Administration, Oral↗

PubMed2002

A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure.

OBJECTIVE: To evaluate the effect of an arteriolar dilator (diltiazem hydrochloride) versus a venodilator (isosorbide dinitrate) on digoxin kinetics and to estimate the efficacy and tolerability of these vasodilators when combined with digoxin for 10 days therapy in patients with congestive heart failure secondary to ischemic heart disease. METHODS: A double blind randomized cross over study was carried out to investigate the effect of an arteriolar dilator (diltiazem hydrochloride 180 mg/day orally) versus a venodilator (isosorbide dinitrate 30 mg/day orally) on digoxin kinetics (0.25 mg/day orally), after 10 days therapy in patients with heart failure due to ischemic heart disease. Also, the effect of these drugs on blood pressure, heart rate, renal functions and serum electrolytes, and their efficacy and tolerability in combination with digoxin were studied. This study was carried out in the Department of Medicine, Main Alexandria University Hospital, Alexandria, Egypt, during the period May 1999 through to May 2000. RESULTS: Diltiazem caused a significant increase in digoxin maximum serum concentration without significant change in time to reach maximum concentration and the apparent volume of distribution. The total digoxin clearance was significantly reduced and the elimination half life was prolonged. Subsequently the area under time-concentration curve and the steady-state digoxin level were increased, but were still within therapeutic margin. On the other hand isosorbide dinitrate significantly increased digoxin maximum serum concentration but without change in the other digoxin pharmacokinetic parameters. Isosorbide dinitrate, but not diltiazem, caused significant reduction in supine and standing blood pressure, while both drugs did not significantly alter pulse rate, renal functions, serum sodium potassium and electrocardiographic pattern. CONCLUSION: Patients who received diltiazem displayed a mean 51% increase in the area under the plasma concentration-time curve, 50% increase in mean steady state serum digoxin concentration, and 37% increase in peak serum digoxin concentration. While patients who received isosorbide dinitrate showed only a 15% increase in digoxin maximum serum concentration and no statistically significant change in mean steady state digoxin concentration or area under the plasma concentration-time curve. The elimination half life during the diltiazem phase was prolonged by 29% while there was no significant change with isosorbide dinitrate. Netiher diltiazem or isosorbide dinitrate significantly altered the time to reach maximum serum digoxin concentration. The addition of a vasodilator such as, diltiazem or isosorbid dinitrate to digoxin could significantly improve the symptoms and signs of heart failure compared to digoxin alone. They were well tolerated and without fear of electrolyte imbalance which potentiate digoxin toxicity.

Analysis of Variance↗

PubMed2003

Serum profile of isosorbide mononitrate after vaginal administration in the third trimester.

Vaginally administered nitric oxide donors such as isosorbide mononitrate have been used to ripen the uterine cervix in pregnancy. The pharmacokinetics of isosorbide mononitrate following vaginal administration are unknown. Serum levels of isosorbide mononitrate were determined at baseline and 60, 180 and 360 minutes after vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women scheduled for induction of labour at term. Serum levels of isosorbide mononitrate continued to rise up to 360 minutes after isosorbide mononitrate insertion, with mean (SD) final levels of 337 (94) microg/L following isosorbide mononitrate 40 mg and 144 (47) microg/L following isosorbide mononitrate 20 mg, P < 0.01.

Abortion, Induced↗

PubMed1983

A comparison of nifedipine and isosorbide dinitrate in angina pectoris with particular reference to arterial oxygen saturation.

To explore beneficial and harmful effects of various combinations of antianginal drugs, we compared antianginal and cardiorespiratory effects of nifedipine and isosorbide dinitrate in low and high doses in combination with nadolol, a long acting beta-adrenoceptor blocker in a double-blind study in 19 patients with stable angina pectoris. Nadolol alone and in combination with the other two drugs reduced anginal attack rate and glyceryl trinitrate consumption; the high dose isosorbide dinitrate showed a further significant (P less than 0.05) reduction in both but the high dose nifedipine did not show such a trend. sigma ST depression (all leads) was significantly (P less than 0.05) more reduced by the high dose nifedipine than by the same dose of isosorbide dinitrate in combination with nadolol. Nadolol reduced forced expiratory volume in one sec (FEV1) slightly and this effect was reversed both by isosorbide and nifedipine. Isosorbide dinitrate in combination with nadolol reduced the basal and post-exercise arterial oxygen saturation (SaO2) whereas nifedipine did not reduce the mean SaO2 below the pre-trial level. A significantly greater sigma ST depression was associated with a lower post-exercise SaO2 (less than or equal to 92%) during all treatment periods but the fall of SaO2 occurred more often during isosorbide than during nifedipine treatment periods. These studies show that both isosorbide dinitrate and nifedipine enhance antianginal efficacy of nadolol. Isosorbide dinitrate, unlike nifedipine, reduces SaO2 which is associated with a greater sigma ST depression.

Adrenergic beta-Antagonists↗

PubMed1983

An open, long-term, multi-centre study of the anti-anginal efficacy and safety of isosorbide 5-mononitrate at low doses in patients with coronary heart disease.

A total of 250 patients with coronary heart disease diagnosed clinically, by ECG and in some cases by coronary angiography, was treated with isosorbide 5-mononitrate, 221 of the patients being treated for up to 6 months. In 181 patients previously treated with isosorbide dinitrate (ISDN)-retard, the mean daily dosage of nitrate was reduced from 77 mg (200 mg maximum) ISDN to 45 mg (120 mg maximum) isosorbide 5-mononitrate in long-term treatment. During previous treatment with ISDN-retard (with high doses in some cases: 80 to 200 mg daily in 48.6% of patients and 40 mg or less daily in only 33.1%), 4.5% of the patients were totally free of angina pectoris attacks. In the same patients, this proportion was 53.6% after administration of isosorbide 5-mononitrate for 6 months (dosage 40 mg daily or less in 67.4% of patients, 80 mg or more in 8.8% of patients). A substantial increase in subjective exercise tolerance and the reduction in incidence of angina pectoris was associated with a marked reduction in nitrate consumption for acute attacks. Isosorbide 5-mononitrate lowered slightly the blood pressure and heart rate. Treatment with isosorbide 5-mononitrate was withdrawn in 22 (8.8%) patients due to nitrate intolerance (headache in 7.6%) and in a further 7 (2.8%) patients for other reasons. Of patients completing 6-months' treatment, 9.9% reported one or more reversible undesirable reactions typical of nitrates at the start of the trial (compared with 6.8% in the pre-trial period). The incidence of such effects decreased to 1.4% after 6 months. The incidence of tolerable headache was 7.7% during the first week on isosorbide 5-mononitrate, decreasing to 0.9% after 24 weeks (5.9% in the pre-trial period). The laboratory parameters and subjective tolerability data confirmed the therapeutic safety of isosorbide 5-mononitrate.

Adult↗

PubMed1979

Simultaneous determination of isosorbide dinitrate and its mononitrates in human plasma by capillary column GLC.

A previously described electron-capture GLC method for determination of isosorbide dinitrate in human plasma was adapted for the simultaneous determination of isosorbide dinitrate, isosorbide 2-mononitrate, and isosorbide 5-mononitrate using a capillary column. Quantitation was done with two internal standards. The lower limits of detection were approximately 0.5 ng/ml of plasma for isosorbide dinitrate, 2 ng/ml for isosorbide 2-mononitrate, and 20 ng/ml for isosorbide 5-mononitrate.

Biotransformation↗

PubMed1994

Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats.

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.

Analysis of Variance↗

PubMed1981

Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure.

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and branchial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (+/- standard deviation) cardiac output at rest from 3.5 +/- 0.5 to 4.9 +/- 1.0 liters/min (p less than 0.01) and decreased arm oxygen extraction from 39 +/- 8 to 33 +/- 10 percent (probability [p] less than 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 +/- 4, hydralazine 60 +/- 12 percent; p = not significant [NS]) or venous lactate during exercise (control 16.6 +/- 7.8, hydralazine 17.1 +/- 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 +/- 0.7 to 4.5 +/- 0.7 liters/min (p less than 0.01) but had no effect on arm oxygen extraction at rest (control 40 +/- 11, isosorbide dinitrate 38 +/- 11 percent; p = NS) and during exercise (control 66 +/- 5, isosorbide dinitrate 64 +/- 8 percent; p = NS) or on venous lactate during exercise (control 17.9 +/- 6.4, isosorbide dinitrate 17.1 +/- 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.

Adult↗

PubMed1987

Comparison of nifedipine and isosorbide dinitrate when added to maximal propranolol therapy in stable angina pectoris.

A study was performed to compare isosorbide dinitrate and nifedipine as adjunctive therapy in 14 patients with coronary artery disease and stable angina pectoris taking maximal beta-blocking drugs. Drug titration phases ensured maximal therapy of propranolol, isosorbide or nifedipine. The combination of nifedipine and propranolol was more effective than the combination of isosorbide and propranolol in reducing angina and increasing exercise capacity (323 vs 416 seconds, p less than 0.005) during exercise treadmill testing. Nifedipine produced a greater reduction in systolic blood pressure at submaximal exercise than isosorbide. Global and regional ejection fraction at rest and exercise was assessed with radionuclide ventriculography. The substitution of nifedipine for isosorbide depressed the global ejection fraction at rest (0.61 to 0.56 p less than 0.05) and produced a slight improvement in exercise ejection fraction (0.47 to 0.51, difference not significant). The decrease in ejection fraction from rest to exercise was 0.14 to 0.04 with nifedipine (p less than 0.005). The benefit of nifedipine compared with isosorbide occurred in regions with marked exercise-induced ischemia. In patients treated with maximal beta-blocking therapy, nifedipine is an effective alternative to isosorbide as a combination agent with propranolol. The salutary effects of nifedipine included afterload reduction with exercise and possible improvements in coronary blood supply.

Angina Pectoris↗

PubMed1988

Effects of isosorbide dinitrate and diltiazem on Ca2+ flux and contraction in artery.

We studied the effects of isosorbide dinitrate and diltiazem on histamine-stimulated 45Ca fluxes and contractions of isolated porcine coronary artery. Isosorbide dinitrate was slightly more potent as an inhibitor of intracellular compared to extracellular calcium-dependent contraction. Isosorbide dinitrate inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction over similar concentration ranges. Isosorbide dinitrate partially inhibited histamine-stimulated calcium influx, but this effect was significant only at high concentration and correlated weakly with inhibition of contraction that was dependent on extracellular calcium. Diltiazem more potently inhibited extracellular vs. intracellular calcium-dependent contraction. Diltiazem partially inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction to similar extents (55-60%) and produced similar concentration-response relationships for inhibition of histamine-stimulated calcium influx and extracellular calcium-dependent contraction. The data suggest that alterations of cellular calcium metabolism are major mechanisms of vascular smooth muscle relaxation by isosorbide dinitrate and diltiazem, but that the specific alterations differ for the two drugs. Isosorbide dinitrate may inhibit contraction primarily by enhancing intracellular calcium sequestration, but possibly also by inhibiting agonist-stimulated calcium influx at high isosorbide dinitrate concentrations. Diltiazem primarily inhibits stimulated calcium influx, but may also inhibit intracellular calcium release.

Animals↗

PubMed1995

Solid-phase extraction of isosorbide dinitrate and two of its metabolites from plasma for gas chromatographic analysis.

A rapid, accurate and selective method for the determination of isosorbide dinitrate and its 2- and 5-isosorbide mononitrate metabolites in 1.0 ml of human plasma has been developed. Before chromatographic quantitation by gas-liquid chromatography with electron-capture detection, the compounds are subjected to solid-phase extraction, using ENVI 18 cartridges (Supelco). The intra-day and inter-day coefficients of variation are less than 10%, except the inter-day coefficient of variation for the assay of 5-isosorbide dinitrate which is less than 15%. Limits of quantitation are 10, 10 and 20 ng/ml for isosorbide dinitrate, 2-isosorbide mononitrate and 5-isosorbide mononitrate, respectively. Recoveries are in excess of 90% for isosorbide dinitrate and 70% for its two metabolites.

Chromatography, Gas↗

PubMed2000

Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI.

PURPOSE: In an effort to improve radiotherapy treatments, methods aimed at increasing the quantity of oxygen delivered to tumors were investigated. The aim of this study was to evaluate the effect of one nitric oxide (NO) donor (isosorbide dinitrate) on pO(2) and blood flow in a murine tumor model. The effect was compared to carbogen, used as a reference treatment. METHODS AND MATERIALS: Thirty-six liver tumors implanted in mouse thighs were imaged using magnetic resonance imaging (MRI) at 4.7 Tesla with dynamic Gd-DTPA and blood oxygen level-dependent (BOLD) contrast-enhanced imaging after administration of isosorbide dinitrate or carbogen. The effect on the pO(2) was also tested by EPR oximetry (1.1 GHz) on 52 mice. RESULTS: A significant increase in MRI intensity was observed for both treatments in comparison with the control group. EPR oximetry showed a dose-dependant increase in tumor pO(2) for isosorbide dinitrate (by 5.9 mmHg at 0.2 mg/kg) and a substantially greater change for carbogen breathing (by 23 mmHg). CONCLUSION: Both tumor blood flow and pO(2) were increased by isosorbide dinitrate and carbogen. Carbogen is more efficient than isosorbide dinitrate in increasing the BOLD image intensity, as well as the tumor pO(2), but as efficient as isosorbide dinitrate in the Gd-DTPA contrast-enhanced imaging. We conclude that the effects of carbogen on improving tumor pO(2) involve both improved blood flow and improved hemoglobin oxygenation, whereas the effects of isosorbide dinitrate are predominantly mediated by improved blood flow alone.

Animals↗

PubMed1994

The antianginal efficacy of isosorbide dinitrate therapy is maintained during diuretic treatment.

OBJECTIVES: To determine whether the use of a diuretic would maintain the antianginal efficacy of isosorbide dinitrate during 1 week of therapy. METHODS: During continuous therapy, organic nitrates have a reduction in antianginal effectiveness and cause fluid retention. The study was a randomized, double-blind, placebo-controlled crossover design examining the effect of 1 week of daily treatment with 50 mg hydrochlorothiazide/5 mg amiloride on the antianginal effectiveness of 30 mg isosorbide dinitrate administered every 6 hours. Exercise stress testing was performed before and 3 hours after administration of isosorbide dinitrate at the start and end of the placebo and diuretic treatment phases. RESULTS: The time to onset of angina (475 +/- 35 versus 490 +/- 29 seconds, difference not significant) and to moderate angina after administration of isosorbide dinitrate (542 +/- 40 versus 566 +/- 37 seconds, difference not significant) were similar at the start and end of the diuretic phase of the study but were reduced at the end of the placebo phase (471 +/- 40 versus 410 +/- 40 seconds, p < 0.05 and 531 +/- 38 versus 466 +/- 39 seconds, p < 0.05, respectively). Total exercise time and time to onset of angina 3 hours after administration of isosorbide dinitrate were longer (p < 0.005) at the end of the diuretic phase compared with the end of the placebo phase. Patients gained weight during the placebo phase and lost weight during the diuretic phase of the study. The change in weight was inversely correlated to the change in total exercise time (r = -0.53, p < 0.05). CONCLUSIONS: Patients using a diuretic with isosorbide dinitrate maintain an increased anginal threshold and total exercise time compared with placebo. Weight change is inversely related to exercise duration, and this result is consistent with fluid retention restoring cardiac preload during nitrate use. The increased anginal threshold during concurrent isosorbide dinitrate and diuretic use may be attributable to maintenance of the organic nitrate-induced reductions in cardiac preload.

Aged↗

PubMed1997

Effects of 3-days' intake of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility.

BACKGROUND: Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained-release preparation of the nitric oxide donor isosorbide dinitrate on swallow-initiated oesophageal contractions and the lower oesophageal sphincter. METHODS: Twelve healthy men, aged 23-32 years, received, at 1-week intervals and under random double-blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side-hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5-mL water swallows were evaluated. RESULTS: Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg +/- 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 +/- 1.0 mmHg) than after placebo (17.9 +/- 1.7 mmHg; P < 0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo. CONCLUSIONS: Twenty and 40 mg sustained-release isosorbide dinitrate twice daily had no effect on swallow-initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.

Adult↗

PubMed1991

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.

BACKGROUND: To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS: Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS: The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Adolescent↗

PubMed1997

Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina. A French multicentre study. French Group of Investigators.

AIMS: Although linsidomine shares common properties with nitrovasodilators, it releases nitric oxide directly without catalytic involvement by thiols. We conducted a prospective, randomized, multicentre, parallel group, single-blind study to compare the efficacy of intravenous administration of linsidomine with that of isosorbide dinitrate in unstable angina. METHODS AND RESULTS: Between November 1990 and July 1992, 568 patients with suspected unstable angina (class IIIB of the Braunwald classification) received a continuous infusion of either linsidomine (1 mg.h-1 on average) or isosorbide dinitrate (2.5 mg.h-1 on average) for 72 h. All patients received concomitant aspirin and intravenous heparin, 81% beta-blockers and 38% calcium antagonists. Holter monitoring was performed in all patients and analysed blindly. Only 25% of the patients had at least one episode of chest pain during the study (24.6% vs 25.8% in the linsidomine and isosorbide dinitrate groups, P = 0.74), of which 12% were associated with ECG changes. Holter criteria yielded similar results in both groups: 33% of patients presented episodes of myocardial ischaemia (32.6% vs 33.9% in the linsidomine and isosorbide dinitrate groups, P = 0.74), while 45% showed episodes of ventricular arrhythmia (43.5% vs 46.5% in the linsidomine and isosorbide dinitrate groups, P = 0.48). The incidence of serious clinical events at 72 h (death, myocardial infarction or myocardial revascularization) was 6.5% (5% vs 8% in the linsidomine and isosorbide dinitrate groups, P = 0.17). CONCLUSION: Intravenous linsidomine is at least as efficacious as isosorbide dinitrate in the stabilization of patients with severe unstable angina.

Aged↗