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1.
Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.  相似文献   

2.
Cardiac L-carnitine content, essential for mitochondrial fatty acid transport and ATP-ADP exchange, decreases during ischemia. In animal models, administration of the natural derivative, L-propionylcarnitine, may reduce ischemia and improve cardiac function. To evaluate possible antiischemic effects of L-propionylcarnitine was compared with placebo in a randomized, double-blind, parallel design, in addition to preexisting therapy. Patients with > or = 2 anginal attacks per week and objective signs of ischemia with angina during bicycle exercise testing were included. After an initial 2-week, single-blind placebo phase, 37 patients received 500 mg L-propionylcarnitine tid, and 37 patients received placebo for 6 weeks. Both groups were comparable at baseline. Three patients discontinued the study while on placebo (two because of noncompliance, one because of palpitations) and one while on L-propionylcarnitine (noncompliance). Although heart rate, blood pressure at rest, and maximal exercise were not affected, L-propionylcarnitine increased the time to 0.1 mV ST-segment depression [44 +/- 3 vs. 8 +/- 2 seconds (mean +/- SEM) in the placebo group; p = 0.05], and exercise duration improved by 5% compared with placebo. Anginal attacks and the consumption of nitroglycerin were not affected in either group. Thus, following a 6 week treatment period, L-propionylcarnitine induced additional, albeit marginal, antiischemic effects in anginal patients who were still symptomatic despite maximal conventional antianginal therapy. It is questionable whether in these patients this form of metabolic treatment will achieve great benefit, although in some improvement can be expected.  相似文献   

3.
Enoximone, a phosphodiesterase inhibitor (PDEI), has both positive inotropic and vasodilatory properties. We examined the effect of a single oral dose of enoximone as compared with placebo on myocardial ischaemia and global left ventricular (LV) function using both exercise ECG and Doppler measurements of aortic blood flow, respectively. Twenty patients (16 men, 4 women) with a mean age of 59 years and stable angina were studied. Total exercise duration was significantly longer after enoximone as compared with placebo treatment, with a mean difference of 22.8 s (p = 0.003). Times (mean +/- SD) to onset of angina and development of significant ST-segment decrease were similar after placebo (454 +/- 101 and 352 +/- 155 s, respectively) or enoximone (500 +/- 155 and 413 +/- 192 s, respectively), although both showed trends in favour of enoximone. As compared with placebo, significantly higher heart rate (HR) was measured for enoximone both at rest (75 +/- 18 vs. 90 +/- 22 beats/min, p < 0.01) and on recovery from exercise (81 +/- 18 vs. 89 +/- 19 beats/min, p < 0.05). Enoximone had no significant effect on systolic or diastolic blood pressure (SBP, DBP) or rate-pressure product (RPP) generated at rest or during exercise. Changes in both acceleration and velocity of aortic blood flow during exercise were similar after administration of enoximone or placebo. We showed that a single oral dose of enoximone is well tolerated in patients with ischaemic heart disease, improving both exercise capacity and favourably influencing ST-segment changes with no increase in adverse events or significant haemodynamic disturbances.  相似文献   

4.
To examine the value of transient regional asynergy on dobutamine stress echocardiography as a noninvasive predictor of future cardiac events, 51 symptomatic patients (aged 54 +/- 9 years) with suspected coronary artery disease (CAD) were studied using an incremental regimen of 5, 10, 15 and 20 micrograms/kg/min. Pretest likelihood of CAD was (mean +/- standard error of the percentage) 79.7 +/- 5.6% before and 83.4 +/- 5.2% after exercise electrocardiography using probability analysis based on age, sex and symptoms. Two-dimensional images were analyzed with reference to an 11-segment model and gave good interrater agreement. During 24 +/- 4 months (range 19 to 32) of follow-up, 23 patients had events (1 myocardial infarction, 9 unstable angina, 10 coronary bypass surgery, 3 coronary angioplasty) and 28 were event free. Age, proportion with baseline asynergy and both pretest echocardiographic ejection fraction and its response to dobutamine were similar in these 2 groups (all p = not significant). Transient asynergy was seen in 17 of 23 patients (74%) with and 8 of 28 patients (29%) without events (p < 0.01); 5 of 6 patients (83%) with involvement of 3 segments had events. Myocardial infarction or unstable angina occurred in 8 of 25 (32%) with a positive and 2 of 26 (8%) with a negative stress echocardiogram (p < 0.05). Both exercise duration (389 +/- 195 vs 517 +/- 237 seconds, p < 0.05) and time to diagnostic ST-segment shift (291 +/- 192 vs 447 +/- 212 seconds, p = 0.05) were shorter in those with inducible asynergy.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

5.
OBJECTIVES: This study was undertaken to determine the effect of a standardized meal on the ischemic threshold and exercise capacity in a series of 20 patients with stable angina, exercise-induced ischemia and reversible exercise-induced perfusion defects. BACKGROUND: It is generally accepted that exercise tolerance in patients with angina is reduced after a meal. However, studies that have addressed this phenomenon have yielded results that are contradictory and inconclusive. METHODS: Two exercise tests using the Bruce protocol with technetium-99m (99mTc)-sestamibi were performed on consecutive days in a randomized order. One test was performed in the fasting state and the other 30 min after a 1,000-calorie meal. RESULTS: In the postprandial state, exercise time to ischemia was reduced by 20% from 248 +/- 93 s to 197 +/- 87 s (p = 0.0007), time to angina by 15% from 340 +/- 82 s to 287 +/- 94 s (p = 0.002) and exercise tolerance by 9% from 376 +/- 65 s to 344 +/- 86 s (p = 0.002). Rate-pressure products at these exercise test end points were not significantly different in the fasting and postprandial tests, and the quantitative 99mTc-sestamibi ischemia score was unchanged. CONCLUSIONS: In patients with stable angina, a 1,000-calorie meal significantly reduced time to ischemia, time to angina and exercise tolerance because of a more rapid increase in myocardial oxygen demand with exercise. The extent and severity of exercise-induced ischemia were unchanged.  相似文献   

6.
Continuous treatment with transdermal nitroglycerin leads to tolerance development within the first day of application. Effective long-term therapy can be provided by interval treatment with nightly patch removal, but even during the hours of intermittent patch application there is rapid attenuation of initial effects. To assess whether an unattenuated antiischemic and antianginal efficacy during the hours of intermittent dosing can be maintained, a modified drug-release profile with increasing plasma concentrations was evaluated using a double-blind, placebo-controlled crossover protocol. Eleven patients with documented coronary artery disease received, in a randomized order, a total of four low-dose nitroglycerin patches (5 mg/24 h each) or placebo, respectively, at intervals of 3 hours. After a treatment interval of 12 hours, all patches were removed for an equally long patch-free interval prior to renewed application of one patch the next morning. At a comparable workload, reductions of ST-segment depression of 65%, 63%, and 56% were found at 2.5 hours, 8 hours, and 12 hours after application of the first patch on day 1, respectively (all significant vs. placebo; 2.5 hours vs. 12 hours, n.s.). On day 2, the comparable reduction of 63% at 2.5 hours after renewed application indicates prevention of tolerance development during subchronic treatment. Effects on exercise capacity and angina pectoris paralleled those on exercise-induced ST-segment depression. Plasma concentrations of nitroglycerin increased from 223 pg/mL to 558 and 803 pg/mL on day 1 and amounted to 205 ng/mL at 2.5 hours on day 2. Thus, interval therapy with increasing nitroglycerin concentrations provides unattenuated antiischemic and antianginal efficacy during the hours of treatment and circumvention of early tolerance during subchronic application. This modified pharmacokinetic profile can be regarded as a model for an improved dosage regimen in nitrate interval therapy.  相似文献   

7.
OBJECTIVE: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. STUDY DESIGN: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV1) > or =70% of the predicted value and a fall in FEV1 > or =20% after exercise on 2 occasions. Patients received montelukast (5-mg chewable tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV1 versus time curve (AAC0-60 min), maximum percent fall in FEV1 from pre-exercise baseline, and time to recovery of FEV1 to within 5% of pre-exercise baseline. RESULTS: Montelukast significantly reduced AAC0-60 min (265 vs 590% x min for montelukast and placebo, respectively, P < or = .05; approximately 59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P < or = .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). CONCLUSIONS: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma.  相似文献   

8.
The pool of controlled clinical studies on mibefradil, a new selective T-type calcium channel blocker, for the treatment of chronic stable angina pectoris was analysed to determine the effects in subgroups of patients defined by age, gender, body weight and common co-existing conditions. Total exercise tolerance test duration increased similarity in all subgroups, both at 50 mg (range 8.9-17.3%; n = 383) and 100 mg mibefradil (range 23.6-30.8%; n = 235). The increases in time to onset of angina and 1 mm ST-segment depression were similarly comparable. Safety and tolerability was similar to placebo for subgroups at 50 mg, but the incidence of adverse events was slightly higher in females, older, and lower weight patients at the 100 mg dose, particularly in reported leg oedema (7.9% in females vs 1.0% in males and 5.1% in older vs 0% in younger patients). Mibefradil proved a safe, well tolerated, and effective antianginal agent that can be used regardless of demographic factors or of frequently coexisting clinical conditions.  相似文献   

9.
BACKGROUND: A variety of vascular effects have been ascribed to 17 beta-oestradiol. These effects may partially explain the reduced incidence of cardiovascular disease found in post-menopausal women on oestrogen replacement therapy. OBJECTIVES: To evaluate the effects of 2 mg sublingual 17 beta-oestradiol on exercise capacity, exercise-induced myocardial ischaemia and circulating levels of endothelin-1 in post-menopausal women with stable coronary artery disease. METHODS: Twelve post-menopausal women, mean age 61 (range 52-72) years, with angiographically verified significant coronary artery disease, were randomly assigned to 2 mg of sublingual 17 beta-oestradiol, 2.5 mg of buccal nitroglycerine and to placebo in a double-blind cross-over study design with at least 2 days between each of the study arms. Antianginal medications, with the exception of beta-blockers, were discontinued before investigation. All study patients underwent a maximal bicycle exercise test 30 min after drug intake. Blood was withdrawn immediately before and up to 8 h after medication for analyses of circulating levels of oestradiol and endothelin-1. RESULTS: The mean serum levels of oestradiol increased from a control level of 72 +/- 28 pmol.l-1 to 3557 +/- 1731 pmol.l-1 after 30 min and to 5028 +/- 3971 pmol.l-1 after 60 min with a gradual decline thereafter. Sublingual 17 beta-oestradiol did not induce any improvement in exercise duration when compared with nitroglycerin and placebo (500 +/- 112 s, 505 +/- 107 s, 498 +/- 157 s), and did not influence time to onset of ST-segment depression (358 +/- 89 s, 436 +/- 93 s, 384 +/- 116 s). The plasma levels of endothelin-1 did not change after administration of 17 beta-oestradiol, nitroglycerin or placebo. CONCLUSIONS: No effects of exercise capacity, exercise-induced acute ischaemia, or plasma levels of endothelin-1 were found after a single dose of 2 mg 17 beta-oestradiol in post-menopausal women with documented coronary artery disease.  相似文献   

10.
BACKGROUND: The aim of this study was to investigate the potential of dexfenfluramine (dF) for reducing cardiovascular risk factors and improving compliance towards diet in a group of young patients hospitalized for essential obesity of high degree (BMI > or = 35). METHODS: 103 adolescents (mean age 15.4 +/- 0.2) participated in a nine-week randomized double-blind study of dF (15 mg bid) versus placebo. All patients received a VLCD (2,512 kJ/day = 600 kcal/day) for two months. In basal conditions, and after 30 and 60 days of treatment, anthropometric variables (height, weight, BMI, and W/H) and cardiovascular risk factors (blood glucose concentration, total cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressure) were monitored. Modifications in hunger and satiety were also assessed. RESULTS: During the treatment period, both the dF group and the placebo group presented a similar pattern of weight loss (BMI = dF: 36.7 +/- 0.5 vs 32.5 +/- 0.4 vs 30.1 +/- 0.4; placebo: 37.0 +/- 0.6 vs 33.1 +/- 0.5 vs 30.8 +/- 0.5). No important side-effects were recorded in either group. Blood pressure and metabolic markers decreased significantly in both groups. Earlier reductions in total cholesterol and diastolic blood pressure in dF-treated subjects were the only significant differences observed as compared to the patients receiving placebo (day 30 = total cholesterol: 120 +/- 2 (dF) vs 132 +/- 3 (placebo) mg/dI; p < 0.005; diastolic blood pressure: 73 +/- 1 (dF) vs 77 +/- 1 (placebo) mmHg; p < 0.01). However, after 60 days, these values were similar in the two groups. As far as non-parametric data are concerned, dF determined a reduction in hunger and an increase in satiety in a significantly higher number of subjects than did the placebo, not only after 30 days of treatment (92.8% vs 55.3% and 92.8% vs 45.5%, respectively; p < 0.0001), but also after two months of treatment (97.8% vs 67.4% and 97.8% vs 45.8%, respectively; p < 0.0001). CONCLUSIONS: These findings demonstrate that dF represents a useful support in the treatment of juvenile obesity and might ensure a better individual compliance towards restrictive diets, particularly in the initial "critical" stages, in the absence of important side-effects.  相似文献   

11.
We evaluated the efficacy and safety of daily administration of gallopamil 150 mg/day and its effects on myocardial perfusion in a medium-term, randomized, double-blind, cross-over, placebo-controlled trial. We studied 19 patients (17 males and 2 females; mean age 57 +/- 6.8 years) with stable effort angina, angiographically documented coronary artery disease and reversible perfusion defects during exercise thallium-201 myocardial scintigraphy of at least one segment of the left ventricle. After 2 weeks of a single-blind placebo run-in period, during which each patient underwent at least 2 exercise tests and a 48-hour Holter ECG recording, all patients were treated with either placebo or gallopamil 50 mg t.i.d. for 28 days. At the end of this period, patients crossed over to the alternate regimen. This phase was double blind. After treatment with placebo or gallopamil, patients underwent exercise tests, 24-hour Holter ECG recording and thallium-201 myocardial scintigraphy. Weekly angina frequency and trinitroglycerin (TNT) consumption and safety were also evaluated. No patients dropped out of the study because of major side effects. The number of total ischemic and symptomatic events recorded at 24-hour ECG monitoring, weekly angina frequency and TNT consumption were significantly reduced during gallopamil treatment. After gallopamil administration, exercise duration significantly increased (run-in: 419 +/- 116 s, placebo: 420 +/- 118 s, gallopamil: 511 +/- 144 s; p < 0.05), and ST segment depression was significantly reduced (run-in: -1.3 +/- 0.3 mm, placebo: -1.3 +/- 0.3 mm, gallopamil: -0.94 +/- 0.68 mm; p < 0.01), while heart rate, systolic blood pressure and rate-pressure product were unchanged at rest, at submaximal and at peak exercise. Qualitative and quantitative evaluation of myocardial perfusion and the myocardial uptake percentage of thallium-201 in ischemic zones were significantly improved by gallopamil treatment. These findings demonstrate that gallopamil can improve myocardial perfusion and reduce myocardial oxygen consumption.  相似文献   

12.
Short-term efficacy of diltiazem in prolonging exercise end points in patients with chronic stable atherosclerosis-associated angina has been demonstrated. The safety and efficacy of diltiazem were examined in a placebo-controlled exercise study over 4 months (eight patients) and subsequently at 12 to 16 months (six patients). Three end points were evaluated: (1) time to onset of angina or fatigue if angina were eliminated; (2) time to 1 mm S-T segment depression or termination of exercise if S-T depression were eliminated; and (3) time to termination of exercise (2+ angina or fatigue). All end points were significantly prolonged over the medium-term 4 month study and decreased again significantly with return to placebo. Maximal effect occurred at 3 months with the first end point increasing from a mean +/- standard error of the mean of 7.2 +/- 1.2 to 10.2 +/- 0.9 minutes (p less than 0.01), the second end point from 8.0 +/- 0.9 to 10.3 +/- 1.0 minutes (p less than 0.01), and the third end point from 9.6 +/- 1.3 to 11.9 +/- 0.8 minutes (p less than 0.05). At 12 to 16 months efficacy was again present. Comparisons for 3 month peak effect with 12 to 16 month long-term effect and subsequent final placebo period were, respectively: first end point, 10.5 +/- 1.3, 9.4 +/- 1.0 and 6.6 +/- 1.7 minutes; second end point, 11.0 +/- 1.3, 10.2 +/- 1.2 and 6.3 +/- 0.7 minutes; and third end point, 12.1 +/- 1.0, 11.0 +/- 1.0 and 9.2 +/- 1.5 minutes. No significant adverse effects of hematologic abnormalities were noted.  相似文献   

13.
Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients treated with oral aminophylline may be different from those treated with high-dose inhaled ipratropium bromide. The purpose of this study was to compare the effects of therapeutic doses of oral aminophylline with high-dose ipratropium bromide on spirometry and exercise tolerance. The study was conducted on three consecutive days in a double-blind, randomized, crossover fashion. Baseline studies obtained on each study day included vital signs, simple spirometry and a symptom-limited maximal cardiopulmonary stress test, after which patients received one of the following treatments on each day: Treatment 1, inhaled ipratropium (total dose of 144 micrograms) with placebo tablets; Treatment 2, inhaled placebo with oral aminophylline (400 mg); Treatment 3, inhaled placebo and placebo tablets. Simple spirometry was repeated at 60 and 120 min after baseline. Vital signs and cardiopulmonary stress testing was repeated at 120 min. Eighteen patients were enrolled in the study, and 17 of these completed the study. There was a significant (P < 0.05) increase in both forced expiratory volume in 1 s (FEV1), from 0.75 (0.21) to 0.92 (0.3), and forced vital capacity (FVC), from 1.8 (0.79) to 2.11 (0.84), with high-dose ipratropium despite prior beta-agonist therapy. Lack of improvement in exercise capacity was noted with ipratropium despite improvement in spirometry. These results suggest that elderly patients with severe COPD may have exercise limitation that is not directly dependent on severity of airflow obstruction. Ipratropium bromide and aminophylline demonstrated no acute effects on exercise capacity.  相似文献   

14.
STUDY OBJECTIVE: To determine the safety and efficacy of diltiazem CD 180 mg administered once/day in patients with chronic stable angina inadequately controlled with P-blockers, long-acting nitrates, or both. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. SETTING: Medical clinics in the private and academic sectors. PATIENTS: Of 172 patients, 170 completed the 2-week double-blind treatment period. INTERVENTION:. Patients received either diltiazem CD 180 mg or placebo once/day in combination with existing antianginal therapy. MEASUREMENTS AND MAIN RESULTS: The time to termination of exercise tolerance testing, 24 hours after the dose increased significantly in the diltiazem CD group (37.2 sec) compared with the placebo group (21.3 sec, p=0.0438). Time to onset of angina during exercise testing also increased (57.6 vs 35.0 sec, respectively, p=0.0324), as did time to moderate angina (37.5 vs 20.6 sec, respectively, p=0.0354). The rates of total angina attacks and of angina attacks on exertion were significantly reduced in the diltiazem CD group versus placebo (p<0.05). Significant reductions in systolic and diastolic blood pressures and heart rate-blood pressure product measured at rest, submaximum exercise, and exercise termination were observed in diltiazem CD-treated patients compared with placebo (p<0.05). The frequency of treatment-related adverse events was identical in the two groups, 15.1%. CONCLUSION: Diltiazem CD 180 mg once/day is an effective, safe, and beneficial initial dosage when added to existing antianginal therapy.  相似文献   

15.
The aim of this study was to assess the prognosis of medically treated patients with "clandestine" myocardial ischemia (perfusion defect without angina and no ST depression > 1 mm during exercise test) compared to those with silent myocardial ischemia (ST-segment depression > 1 mm, without angina) and those with angina pectoris. One hundred twelve patients without previous myocardial infarction were included. All patients underwent a symptom-limited exercise test on a bicycle ergometer, myocardial perfusion technetium-99m-methoxy-isobutyl-isonitrile single-photon emission computed tomography (SPECT), and coronary angiography. They were classified into 3 groups (angina group, 34 patients; silent group, 20 patients; and the clandestine group, 58 patients). The mean follow-up was 3.6 years (range 6 months to 5.5 years). Patients with clandestine ischemia had a lower scintigraphic and angiographic score than patients with silent ischemia (25+/-8 vs 31+/-9 and 24+/-8 vs 29+/-7, p = 0.008, respectively), but the prognosis was similar. Only angina and severe reversible SPECT defects were predictive for cardiac events: death + myocardial infarction + revascularization. We conclude that in medically treated patients without previous myocardial infarction, angina and severe reversible SPECT defects are predictive for cardiac events only when the need for revascularization is included as a cardiac event.  相似文献   

16.
OBJECTIVES: To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.  相似文献   

17.
OBJECTIVES: We sought to evaluate the effects of intermittent transdermal nitroglycerin (TD-NTG) on the occurrence of ischemia during patch-off hours in patients with stable angina pectoris receiving a beta-adrenergic blocking agent or calcium antagonist, or both. BACKGROUND: The current recommendations for the use of intermittent TD-NTG may be associated with the occurrence of rebound ischemia. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, crossover trial with three study periods. Tolerability to TD-NTG was assessed in Period I. Seventy-two patients were assigned to receive either double-blind transdermal placebo or maximally tolerated TD-NTG for 2 weeks (Period II) and were then crossed over to the alternative treatment for another 2 weeks (Period III). The patients were instructed to apply medication daily at 8 AM, to remove it at 10 PM and to note symptoms and sublingual nitroglycerin (SL-NTG) use in a diary. The occurrence of ischemia was assessed from patient-perceived angina, symptom-limited exercise treadmill test (ETT) and 48-h ambulatory electrocardiographic (AECG) monitoring. RESULTS: Transdermal NTG (0.2 to 0.4 mg/h) significantly reduced the magnitude of ST segment depression at angina onset during ETT compared with placebo. Total angina frequency was not significantly different between TD-NTG (mean [+/-SD] 3.2 +/- 4.2) and placebo (3.3 +/- 5.2). During patch-off hours, angina frequency increased with TD-NTG (1.1 +/- 2.1) compared with placebo (0.7 +/- 1.6) (p = 0.03). Similar trends for an increase in ischemia after TD-NTG were also observed from AECG analyses. Specifically, ischemia frequency tended to be lower during patch-off hours for placebo than with TD-NTG (0.05 +/- 0.09 vs. 0.08 +/- 0.20 episodes/h, respectively, p = 0.08), even though frequency of ischemia tended to be higher during patch-on hours for placebo than with TD-NTG (0.12 +/- 0.19 vs. 0.07 +/- 0.15 episodes/h, respectively, p = 0.11). During placebo, ischemia frequency decreased 58% (patch-on to patch-off, p = 0.01) compared with a 14% increase with TD-NTG. These changes attenuate the usual circadian variation in ischemia. CONCLUSIONS: An increase in ischemia frequency during patch-off hours after use of intermittent TD-NTG was perceived by patients, and this subjective finding was supported by a corresponding trend for AECG ischemia to increase during these same hours.  相似文献   

18.
A multicenter, randomized, double-blind, crossover, placebo-controlled study was conducted in 90 isosorbide dinitrate responders showing stable angina to compare the efficacy of molsidomine retard, 8 mg b.i.d., with that of molsidomine, 4 mg t.i.d., for 6 weeks. Total work performance (workload x min) was significantly improved, compared with baseline and placebo until 8 and 12 h after molsidomine and molsidomine retard administration, respectively. ST-segment depression decreased significantly under the two treatments at 60 W as well as at maximal exercise. The rate-pressure product (heart rate x systolic blood pressure) decreased and increased significantly at submaximal and maximal exercise level, respectively. All these effects remained significant after 6-week treatment, with only the ST segment showing a nonsignificant tendency to improvement at maximal work. The frequency of anginal attacks and of sublingual nitroderivative-tablets consumption decreased significantly with molsidomine, 4 mg, and molsidomine retard, 8 mg. However, overall results showed that the latter form reduces myocardial ischemia more efficiently at submaximal exercise level, has a more prolonged effect on exercise tolerance, and maintains it at a somewhat higher level after 6-week treatment.  相似文献   

19.
We evaluated the effects of a Ginkgo biloba/ginseng combination on cognitive function in this 90-day, double-blind, placebo-controlled, parallel-group study. Sixty-four healthy volunteers (aged 40 to 65 years), selected on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia, were assigned randomly to four equal dosing groups, receiving 80, 160, or 320 mg of the combination b.i.d. or placebo. Assessments were performed on the day before dosing, and again at Days 1, 30, and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose. The assessments included the Cognitive Drug Research (CDR) computerized assessment system, the Vienna Determination Unit, cycle ergometry, and various questionnaires. The treatments were well tolerated by all volunteers. On Day 90 at 1 hour post morning dosing, dose-related improvements were seen on the CDR tests, the 320 mg dose being significantly superior to placebo. These effects, however, were reversed 1 hour after the afternoon dose, possibly suggesting that a longer inter-dosing interval would be preferable. The 80-mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load. There were also several supporting changes from other assessments, including an advantage of 320 mg over placebo on the global score from the Symptom Checklist-90-revised (SCL-90-R) at Day 90.  相似文献   

20.
OBJECTIVES: To evaluate the efficacy and safety of two once-daily doses of tamsulosin, the first selective alpha1A-antagonist studied in clinical trials. METHODS: Patients with benign prostatic hyperplasia (BPH) were randomized to receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary efficacy parameters were improvement in the total American Urological Association (AUA) symptom score and peak urinary flow (Qmax). Secondary efficacy parameters were improvement in measurements at individual double-blind visits corresponding to the primary efficacy parameters; percentage of patients with a 3-mL/s increase in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA symptom scores; total, irritative, obstructive, and individual Boyarsky symptom scores; average urinary flow rate and other uroflowmetric parameters; and investigator's global assessment. RESULTS: Statistically significant improvements in all efficacy parameters were observed in tamsulosin-treated compared with placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind medication. A review of the safety parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group. CONCLUSIONS: Tamsulosin was effective, safe, and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels, without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists.  相似文献   

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