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Biomedical subjects

A Schneeweiss

Publications and source records attributed to A Schneeweiss.

At least 19 recordsLinked to original sources
PubMed1995

Differences in ischemic threshold and nitrate efficacy between normotensive and hypertensive patients with stable angina pectoris.

The coexistence of ischemic heart disease with hypertension makes antihypertensive therapy essential, since relief of hypertension may ameliorate the coronary disease. On the other hand, the effect of antianginal nitrate therapy in patients with stable angina pectoris and systemic arterial hypertension is not fully understood. This study assessed the effects of hypertension on the ischemic threshold and the time to moderate angina, measured as parameters of nitrate efficacy. In this double-blind, parallel-group study, 141 patients with stable angina pectoris were randomly assigned to receive 5 mg, 10 mg or 20 mg isosorbide-5-mononitrate or matching placebo bid for 21 days. Ninety-three normotensive and 48 hypertensive patients were compared with regard to the time to moderate anginal pain and the ischemic threshold before and after nitrate treatment on the first day of the study. The acute nitrate effect 2 h after drug administration was substantially attenuated in hypertensives at both 10 and 20 mg of isosorbide-5-mononitrate, with the time to moderate anginal pain being significantly shortened. Impaired vasodilatator response of the arterial vasculature to organic nitrates, probably due to impaired biotransformation of organic nitrates to nitric oxide in hypertensive patients, is suggested as a possible mechanism for the diminished nitrate effect. Thus, oral nitrate therapy does not have the same beneficial antianginal effect in hypertensive patients as it does in normotensives. Dose adjustment based on the pretreatment blood pressure, and the administration of higher doses of oral nitrates should therefore be considered in hypertensive patients suffering from stable angina pectoris.

Aged↗
PubMed1994

[Isosorbide-5-mononitrate in angina pectoris: its efficacy and absence of tolerance and rebound with an eccentric type of administration].

UNLABELLED: 214 patients with angina pectoris were randomized to placebo or isosorbide-5-mononitrate (ISMN) rapid release 5, 10 or 20 mg b.i.d. at 8 a.m. and 3 p.m. Exercise tests were performed between 8 a.m. and 10 p.m., before and 2 and 7 h after each dose on days 2 and 14 and before and 2 h after the morning dose on days 7 and 21. All doses of ISMN increased exercise duration significantly more than placebo, and this effect lasted throughout most of the day. It was maximal (73 s; 24%) 2 h after the morning dose, slightly attenuated but still significant at 7 h, increased 2 h after the second dose and attenuated but still greater than with placebo at 7 h. The increase was even greater at 3 weeks (99 s; 29%), perhaps due to a training effect. Similar improvement was observed in other exercise parameters. There was no significant dose response. There were 100% more anginal attacks in the placebo than in the 20-mg treatment group. No rebound (assessed by comparing exercise duration before the morning dose between the groups) was observed. CONCLUSION: ISMN b.i.d. eccentrically has an antianginal effect throughout most of the day, peaking at 2 h. This effect is sustained during chronic therapy, without tolerance or rebound.

Adult↗
PubMed1993

Haemodynamic and neurohumoral effects of flosequinan in severe heart failure: similarities and differences compared with intravenous nitroglycerin therapy.

The acute haemodynamic and neurohumoral effects of flosequinan, a new direct-acting vasodilator, were studied in 12 patients with severe (eight in New York Heart Association grade 3, four in grade 4) cardiac failure. Flosequinan was administered in a single oral dose of 100 mg, with haemodynamic monitoring over a 22 h period. The effects were compared with those observed during high dose intravenous nitroglycerin therapy (276 +/- 100 micrograms.min-1), given to the same patients for an identical period on the previous day. Both flosequinan and nitroglycerin produced significant haemodynamic improvement during the 22 h monitoring period. Cardiac and stroke indices increased with both drugs. However, while systemic and pulmonary vascular resistance were reduced similarly by both drugs, the decrease in right atrial and pulmonary capillary wedge pressures was greater with nitroglycerin and less with flosequinan, indicating a greater venodilator effect for nitroglycerin and a more balanced arterial and venodilator effect for flosequinan. Systemic arterial pressure and heart rate tended to increase with flosequinan and to decrease with nitroglycerin. In contrast to nitroglycerin, flosequinan did not increase plasma renin activity and serum aldosterone levels. Atrial natriuretic peptide decreased appropriately after both drugs, in keeping with the decreases in left and right heart filling pressures. The favourable haemodynamic and neurohumoral profiles of flosequinan suggest that it may be a useful vasodilating drug in the management of patients with severe heart failure.

Administration, Oral↗
PubMed1993

Effect of sotalol on arrhythmias and exercise tolerance in patients with hypertrophic cardiomyopathy.

The effect of sotalol on exercise tolerance and incidence of arrhythmias was studied in 30 patients with hypertrophic cardiomyopathy (HCM). In this short-term, double-blind, cross-over study, exercise time on sotalol (320 mg/day) was significantly longer than on placebo (10.6 +/- 4.0 vs. 9.4 +/- 3.6 min; p < 0.01). Sotalol eliminated supraventricular arrhythmias in 6 of 7 patients (p < 0.03) and suppressed ventricular arrhythmias in 7 of 13 patients in whom they were present on placebo (p < 0.05). Ventricular tachycardia was abolished in 4 of 8 patients, but appeared during sotalol treatment in 1 patient who was free of repetitive arrhythmias on placebo. Twenty-five patients who had better exercise tolerance on sotalol than on placebo and did not experience aggravation of arrhythmia entered a 6-month prospective, open-label treatment with sotalol (160-480 mg/day, mean +/- SD 377 +/- 94). One patient was withdrawn after 1 month because of bronchospasm. Mean exercise time improved from 9.8 +/- 3.6 min on placebo to 12.7 +/- 3.2 min (p < 0.01) after 6 months of treatment with sotalol. During the prospective follow-up, sotalol abolished ventricular tachycardia in all 6 patients after 1 month (p = 0.022), and in 4 of 6 patients (p > 0.2) after 6 months of treatment. It is concluded that sotalol significantly improves exercise tolerance and is effective in suppressing both supraventricular and ventricular arrhythmias in patients with HCM.

Adolescent↗
PubMed1993

A non-invasive evaluation of flosequinan on haemodynamics and exercise capacity in chronic congestive heart failure.

The efficacy of flosequinan 100 mg once daily was evaluated in 15 patients with severe congestive heart failure (New York Heart Association [NYHA] class II-IV) who had not responded adequately to digoxin and diuretics. Efficacy assessments using non-invasive techniques included exercise capacity, haemodynamics and left ventricular function. Determinations were made after 3 and 21 days' treatment, and compared with baseline. Flosequinan significantly increased exercise capacity by 27% after 3 days (+79 seconds, p = 0.015) and by 43% after 21 days (+123 seconds, p = 0.0007) and was accompanied by an increase in heart rate (+7.2 beats/min, p = 0.03; +9.1 beats/min, p = 0.03, respectively). Cardiac index and cardiac output were also significantly increased but only after 21 days' treatment (+0.3 l/min/m2, +16% and +0.5 l/min, +14%, respectively; both p = 0.008). Flosequinan was well tolerated, with headache being the most frequently reported adverse event and only 1 patient being withdrawn. One patient died but this was not unexpected in a group of patients with severe heart failure. Using non-invasive techniques this study demonstrated that in patients with severe chronic congestive heart failure, flosequinan increased exercise capacity and cardiac output, the latter being achieved mainly by an increase in heart rate.

Aged↗
PubMed1992

Usefulness of intracoronary isosorbide dinitrate in alleviating myocardial ischaemia during coronary balloon angioplasty.

The effect of intracoronary isosorbide dinitrate on provoked myocardial ischaemia during percutaneous transluminal coronary angioplasty (PTCA) was studied in 60 patients who had at least 1 mm electrocardiographic (ECG) ST segment deviation during a 70 s control balloon inflation period. Isosorbide dinitrate (dose 1 mg, 2 mg or 3 mg) or placebo (saline) was administered by slow intracoronary injection, and the ST segment changes recorded again during an identical dilatation period 2-4 min later. Following injection of isosorbide dinitrate, the severity of ST segment deviation decreased (1 mg -31 +/- 30%, P = 0.03; 2 mg -51 +/- 35%, P = 0.0001; 3 mg -36 +/- 32%, P = 0.002) during coronary balloon inflation, and the time until onset of 1 mm ST deviation was prolonged (1 mg +79 +/- 137%, P = 0.06; 2 mg +85 +/- 87%, P = 0.02; 3 mg +78 +/- 109%, P = 0.02). With the 3 mg dose, the time to maximum ECG change increased (+37 +/- 87%, P = 0.02). In the placebo group, there was a small decrease in the severity of ST segment deviation in patients receiving placebo (-23 +/- 32%, P = 0.03), but no change in the time to its onset or in the time to maximum ST deviation. Isosorbide dinitrate did not alter heart rate, systolic arterial pressure or the rate-pressure product at maximum ST segment change, implying that when isosorbide was administered by direct intracoronary injection, a direct cardiac effect was responsible for the major anti-ischaemic effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1992

Cilazapril: an overview of its efficacy and safety in hypertension.

Cilazapril is a new once-daily angiotensin-converting (ACE) enzyme inhibitor which has been administered to 4,500 patients with mainly mild to moderate essential hypertension in a multinational clinical research program. Sitting diastolic blood pressure was reduced by about 9 mm Hg from baseline (p less than 0.01) after 4 weeks of treatment with cilazapril 1.25-10 mg/day in double-blind placebo-controlled studies. Total responder rates to cilazapril were usually 50-60% compared with 30% to placebo. Adding hydrochlorothiazide 12.5 mg/day to cilazapril 5.0 mg/day increased the total responder rate from 52 to 71%. Double-blind dose titration studies for 8 weeks showed that cilazapril 2.5-5 mg/day possessed equivalent efficacy to usual therapeutic regimens of sustained release propranolol, captopril, hydrochlorothiazide, atenolol and enalapril, Cilazapril did not affect heart rate. During long-term open administration for 52 weeks, or longer, cilazapril, either alone or in combination with hydrochlorothiazide, effectively maintained control of blood pressure. Treatment of patients with severe hypertension with cilazapril plus hydrochlorothiazide achieved a total responder rate of 73%. Adverse events were mostly observed within the first 8-16 weeks of treatment, with headache, dizziness, fatigue, nausea, cough and chest pain being the most frequent. Non-life-threatening angioedema, facial edema and mild hypotension occurred in less than or equal to 0.2% of patients, and orthostatic hypotension was reported in 2%. Abnormal laboratory test values were rarely found with cilazapril treatment. Of the 2.3% of patients with elevated serum creatinine, at any time point during the study and irrespective of outcome on continuation with cilazapril therapy, about two thirds had prior renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Complete spontaneous remission of cough induced by ACE inhibitors during chronic therapy in hypertensive patients.

The files of 172 consecutive hypertensive patients who received captopril or enalapril have been reviewed and the patients questioned on the development of chronic dry cough, persisting for at least two months. Forty patients had cough that was attributed to the drugs. Thirteen of them discontinued the drugs because of this adverse effect. In 15 of the 27 patients (55%) who continued receiving ACE inhibitors (7 males, 8 females, aged 65.4 +/- 9.9 years) the cough had spontaneously disappeared after 3.9 +/- 1.9 months of continued unaltered administration of these drugs and without any treatment aimed against this symptom. All patients were followed for at least four months after disappearance of cough, without recurrences. This finding may discourage withdrawal of ACE inhibitors from many patients who develop cough. Continuation of ACE inhibitors for at least several months, despite cough, (if the cough is not too severe) is probably justifiable.

Aged↗
PubMed1991

Comparative evaluation of the effect of afterload- and preload-reducing drugs on diastolic cardiac function in hypertensive patients.

The effects of cilazapril, isosorbide-5-mononitrate (ISMN), hydrochlorothiazide and placebo on systolic and diastolic cardiac function were studied to evaluate the relative importance of afterload and preload reduction on cardiac function in hypertensive patients. In 86 patients with essential hypertension, radionuclide studies were performed before and after a single oral dose of placebo (18 patients), cilazapril 2.5 mg (35 patients), ISMN 20 mg (18 patients) or hydrochlorothiazide 25 mg (15 patients). The effects on blood pressure, heart rate, left ventricular ejection fraction, peak filling rate and time to peak filling rate were measured. Placebo had no significant effect. A comparable blood-pressure-lowering effect was achieved with cilazapril and hydrochlorothiazide. Cilazapril improved diastolic function by increasing the normalized peak filling rate from 2.3 +/- 0.7 to 2.7 +/- 0.7 vol/s (p less than 0.05) and reducing the time to PFR from 174.5 +/- 33.6 to 152.4 +/- 30.8 ms (p less than 0.005). Hydrochlorothiazide and ISMN, however, impaired left ventricular diastolic function: hydrochlorothiazide decreased the normalized peak flow rate from 2.2 +/- 0.6 to 1.9 +/- 0.6 vol/s (p less than 0.05). ISMN prolonged the time to peak flow rate from 176 +/- 36 to 195 +/- 29 ms and increased the percentage of diastole to peak flow rate from 46 to 53% (p less than 0.05), whereas the normalized peak flow rate was unaltered. In conclusion, predominant afterload reduction by cilazapril improves left ventricular diastolic function in hypertensive patients, while preload reduction by diuretics and nitrates impairs it.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Anti-ischemic effects of cilazapril in patients with both hypertension and angina pectoris. Preliminary report of a pilot study.

We report the preliminary findings in the first 12 patients enrolled in a double-blind randomized placebo-controlled study of the antianginal effect of the new angiotensin-converting enzyme inhibitor, cilazapril (2.5 mg once daily) in patients with both hypertension and angina pectoris. After 3 weeks of treatment, placebo had no effect whereas cilazapril significantly prolonged exercise duration. In 2 of the patients on cilazapril, exercise duration was markedly prolonged from 387 to 534 and 352 to 556 s. The maximal ST segment depression was unaltered. It is suggested that in selected patients with both hypertension and angina pectoris cilazapril may have an antianginal effect. A larger study is now underway.

Angina Pectoris↗
PubMed1990

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease.

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

Adult↗
PubMed1990

Individualized antianginal therapy guided by systemic arterial pressure.

All antianginal drugs except nitrates are also first-line antihypertensive drugs. Their antianginal efficacy has not been evaluated in relation to pretreatment blood pressure. They may aggravate ischemia due to excessive reduction in blood pressure. Until the results of direct comparative studies are available, it is advisable to start treatment of angina pectoris in normotensive and hypotensive patients with other drugs that do not primarily decrease blood pressure. Nitrates are a reasonable choice.

Adrenergic beta-Antagonists↗
PubMed1990

Evaluation of the efficacy and duration of action of isosorbide mononitrate in angina pectoris.

The magnitude and duration of the antianginal and anti-ischemic effects of isosorbide mononitrate (IS-5-MN), 20 mg, were determined in 10 patients with chronic stable angina pectoris. An exercise test (treadmill, Bruce protocol) was performed before and at 1, 6, 8 and 10 hours after oral administration of the drug. The patients were randomly assigned to receive IS-5-MN or placebo, and after 1 week of therapy were crossed over to the other formulations. The drug increased the exercise duration from 321 to 455 seconds at 1 hour (p less than 0.001). Time to moderate angina increased from 237 to 324 seconds (p less than 0.05) and time to ST depression greater than or equal to 1 mm increased from 150 to 307 seconds (p less than 0.01) at 1 hour. Placebo had no effect on any of the exercise parameters. Although partially attenuated at 6 hours, the effect of IS-5-MN remained statistically significant even at 8 hours, but not at 10 hours. It is concluded that the duration of action of a single tablet of IS-5-MN, given orally, is 8 hours.

Adult↗
PubMed1990

Nitrate tolerance in heart failure: differential venous, pulmonary and systemic arterial effects.

The hemodynamic profile of tolerance to intravenous nitroglycerin was studied in 9 patients with New York Heart Association Class III to IV congestive heart failure. After rapid dosage build-up to the maximal tolerated dose (decrease in pulmonary wedge pressure to 10 mm Hg or systolic blood pressure to 90 mm Hg), nitroglycerin (525 +/- 548 micrograms/min) was administered at a constant continuous intravenous infusion for a total of 24 hours. The extent of nitrate tolerance at 24 hours was calculated as the percentage loss of the benefit achieved at time of peak effect of nitroglycerin. Tolerance had a different time course and magnitude in the venous, arterial and pulmonary circulations. At 24 hours, right atrial pressure and pulmonary vascular resistance returned to control values in most patients, while 40 to 50% of the effect on systemic vascular resistance, cardiac index and pulmonary wedge pressure was maintained. These findings emphasize the importance of precise definitions in studies relating to nitrate tolerance.

Adult↗
PubMed1990

Efficacy of isosorbide-5-mononitrate on painful and silent myocardial ischemia after myocardial infarction.

The anti-ischemic efficacy of isosorbide-5-mononitrate, 20 mg 3 times daily, on silent myocardial ischemia after myocardial infarction was studied in 28 Chinese patients with use of 48 hours of ambulatory electrocardiographic monitoring in a randomized, crossover, single-blind, placebo-controlled study. Isosorbide mononitrate reduced both painful and painless episodes of ischemia compared with placebo. The number of total ischemic episodes was reduced 88%, duration of ischemia 94%, time-ischemia integral 95%, and total maximal ST-segment depression 86% (p less than 0.01). The drug did not alter the heart rate and blood pressure, and had no evident adverse effect. Thus, isosorbide mononitrate is effective and well tolerated in postinfarction patients with silent ischemia.

Adult↗
PubMed1990

Hemodynamic and coronary vasodilative action of two nitroglycerin oral spray formulations.

This study compared glycerol trinitrate (NTG) oral spray in a new hydrophilic formulation with a reference aerosol in a lipophilic base with respect to the time to onset of action on hemodynamics and on the coronary vasomotor tone. Differences in the profile of action between the two spray formulations were assessed in two groups of ten patients each. In each of the two groups the patients were randomly assigned to receive 0.8 mg of aerosolized NTG in either the hydrophilic or lipophilic base in double-blind fashion. The patients of group A had stable, exercise-induced angina pectoris, in whom responses to the sprays were evaluated under resting conditions. The patients of group B were suspicious of vasospastic or mixed form of angina pectoris, in whom the effects of the sprays were studied under diagnostic ergonovine provocation. The onset and extent of action of the sprays were assessed by serial measurements of hemodynamic parameters and repeat quantitative coronary angiography. The two formulations of NTG oral spray had a comparably potent coronary vasodilator effect in patients under resting conditions and under ergonovine provocation. As far as hemodynamic action is concerned, the new hydrophilic spray exerted its hemodynamic effect more rapidly than the lipophilic spray. Thus, the new NTG oral spray promises to afford therapeutic advantages for the relief of anginal attacks as well as hemodynamic unloading in congestive heart failure and acute pulmonary hypertension.

Administration, Oral↗