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Left ventricular remodelling and haemodynamic effects of multisite biventricular pacing in patients with left ventricular systolic dysfunction and activation disturbances in sinus rhythm: sub-study of the MUSTIC (Multisite Stimulationin Cardiomyopathies) trial.

AIMS: To use echocardiography to determine early and late haemodynamic effects of atrio-biventricular (A-BiV) pacing on left ventricular (LV) function and their interrelations with exercise tolerance. METHODS: Thirty-four patients with ejection fraction <35% (18 idiopathic dilated cardiomyopathy (DCM) and 16 ischaemic cardiomyopathy, in sinus rhythm and with intra-ventricular conduction delay (IVCD)) were implanted with transvenous A-BiV pacemakers. Echocardiographic measurements were compared before implantation, after 3 months A-BiV pacing, and 3 months inactive pacing (ventricular inhibited pacing at 40 beats x min(-1)as part of a crossover design, and at 9- and 12-month longitudinal follow-up. RESULTS: Total isovolumic time (IVT) halved after 3 months A-BiV pacing (from 20.1+/-4.4 to 10.7+/-4.9s min(-1), P<0.001) and did not change thereafter. LV cavity size fell after 3 months (end-diastolic dimension (EDD) 7.3+/-0.8 to 6.8+/-0.8 cm, P<0.001, and end-systolic dimension (ESD) 6.2+/-0.8 to 5.9+/-0.8 cm, P<0.05), with a further fall in EDD and ESD (by 8.4+/-7.8 and 8.8+/-7.8mm, respectively, both P<0.001) after 12 months. Although not a primary end-point of the study, the 12-month reduction in LVEDD and LVESD was greater in idiopathic DCM (by 8.9 and 9.8mm, P<0.01, respectively) compared with ischaemic cardiomyopathy. The 6-min walk rose by 15% (P<0.01) and peak VO(2)by 10% (P<0.05) after 3 months, with no further increase by 12 months, and no difference between idiopathic DCM and ischaemic cardiomyopathy. The increase in peak VO(2)at 12 months correlated with the fall in ESD (r=0.47, P=0.03). CONCLUSIONS: A-BiV pacing shortens total IVT, reduces LV cavity size, and increases exercise tolerance in patients with DCM and IVCD. Ischaemic cardiomyopathy does not affect the exercise response, although it does reduce the extent of reverse remodelling.

Aged↗

Comparison of resting hemodynamic indices and exercise performance during atrial synchronized and asynchronous ventricular pacing.

Resting hemodynamic indices and exercise tolerance were measured during atrial synchronized (VAT) and asynchronous ventricular pacing (VOO) in 35 patients with implanted pacemakers which could be externally programmed to function in either pacing mode. Cardiac output and mean systemic arterial pressure were significantly greater during VAT pacing (VAT: 4.5 +/- 1.2 1/min, 115 +/- 28 mmHg; VOO: 3.7 +/- 0.8 1/min 105 +/- 25 mmHg respectively), although there was no difference in pulmonary artery end-diastolic pressure. Maximal exercise performance was assessed using the Bruce protocol in both pacing modes. Neither the patient nor the supervising physician was aware of the preselected pacing mode; a second physician monitored the electrocardiogram and blood pressure but influenced the point of exercise termination only if a potentially dangerous arrhythmia or hypotension occurred. Blood pressure responses were superior and atrial rates lower during VAT pacing. In all but five patients, exercise tolerance was improved by VAT pacing. This amounted to 33 percent or more in 23/35 patients. This improvement was shown to be maintained in the 20 patients who had repeat exercise tests several weeks later. Ventricular arrhythmias, hypotension, and lightheadedness frequently complicated exercise during asynchronous pacing but occurred rarely with atrial synchronized pacing. Resting hemodynamic indices did not predict the extent of improvement gained by physiological pacing.

Adult↗

Exercise performance of polycythemic chronic obstructive pulmonary disease patients. Effect of phlebotomies.

The purpose of this study was to determine the effects of phlebotomy on the exercise tolerance and right and left ventricular ejection fraction of polycythemic patients with chronic obstructive pulmonary disease. Ten patients with COPD (mean FEV1 = 1.32 +/- 0.55 L) and polycythemia (mean Hct = 62 +/- 3 percent) were studied before and after their hematocrits had been reduced to approximately 50 percent. Post-phlebotomy the maximal oxygen consumption increased from 1.09 +/- 0.34 L/min to 1.26 +/- 0.43 L/min (p less than 0.05) and the maximum workload increased from 56.5 +/- 32.6 watts to 74.5 +/- 23.4 watts (p less than 0.05). The increase in the exercise tolerance appeared to be primarily due to an increased cardiac output at Emax. There was no relationship between the increases in the upright exercise capacity and changes in the supine ejection fractions of the right or left ventricular either at rest or during exercise.

Aged↗

Functional results of muscle flap closure for sternal infection.

The morbidity and mortality of infection after median sternotomy have been substantially reduced with the advent of treatment by wide sternal resection and muscle flap closure. A study was performed comparing the cardiorespiratory function of 13 such patients before and after operation as well as with a control group of 15 patients who underwent similar procedures without complication. The groups were comparable in preoperative pulmonary function, though more patients in the study group had evidence of chronic lung disease. Patients were studied 2 to 39 months after the original procedure. Late postoperative pulmonary function test results, exercise tolerance, and oxygen uptake were not significantly different between the groups, and pulmonary function test results were unchanged in those patients who were tested preoperatively. We conclude that muscle flap reconstruction for sternal infection can be expected to give good long-term functional results. Exercise tolerance and pulmonary function may not differ from a control group of cardiac surgical patients, despite the altered composition of the chest wall. Patients with chronic lung disease may be more prone to have this complication.

Aged↗

Dynamic stress echocardiography in asymptomatic patients who received chemotherapy in childhood because of a malignant disease.

BACKGROUND: Introducing anthracycline antibiotics into the treatment of children's malignancies contributed enormously to the excellent outcome in children and adolescents. Nevertheless, the cardiotoxicity of such was discovered as early as in the 1970's. Only recently stress tests have been used to detect late cardiotoxic effects of anti-neoplastic drugs. AIM: To determine the function of the left ventricle (LV) in asymptomatic patients who were treated with chemotherapy containing anthracyclines in childhood or adolescence. METHODS: We examined 137 patients (81 men, 56 women), aged 16.6+/-4.8 years, in whom a malignant disease was diagnosed at the age of 9.1+/-4.8 years and who were treated with a cumulative dose of anthracyclines of 242+/-110 mg/m(2). The control group comprised 30 subjects (14 men, 16 women, mean age 19.5+/-5.2 years). The echocardiographic examination was carried out at rest and also immediately after a dynamic stress test. RESULTS: A decrease in the fractional shortening (FS) <30% was found in 11 (8%) patients. The values of ejection fraction (EF), mean velocity circumferential fibre shortening, end-systolic wall stress, excursion and systolic thickening of the LV posterior wall were significantly impaired in comparison with the group who had the FS > or =30% as well as with the control group. The maximal decrease in EF was reduced to 40% and FS - to 20%. The values of the index of the global function of LV were, in comparison with the control group, impaired in both subgroups of the patients. We did not find any differences in the exercise tolerance between the groups. The EF values both at rest and at stress were significantly lower in the group with FS <30% when compared with other groups. The values of percentage EF stress increment were increased in all the groups. A decrease in EF after exercise was not observed. CONCLUSIONS: Anthracycline chemotherapy leads to a late impairment of LV function. Asymptomatic patients with a decrease of EF to 40% or FS to 20% show preserved exercise tolerance as well as contractile reserve of the LV. These findings represent a better prognosis for the patient. Echocardiography at rest should be carried out repeatedly after the termination of the treatment and in the case of a pathological finding it is necessary to perform stress tests to evaluate the contractile reserve.

Adolescent↗

Ventilatory inefficiency for carbon dioxide during exercise in patients with pulmonary hypertension.

The purpose of this study was to analyse the ventilatory efficiency for carbon dioxide (CO2) in the assessment of exercise tolerance in patients with pulmonary hypertension. Two groups of patients were studied. One group consisted of 37 patients with normal pulmonary artery pressure who underwent surgical closure of a left-to-right shunt. Another group was composed of 10 patients with pulmonary hypertension. Both patient groups were compared with the mean value of an age-matched pool of normal control subjects. Aerobic exercise performance was assessed by determination of the ventilatory threshold. The ventilatory efficiency for CO2 was assessed by calculating the slope of ventilation over carbon dioxide below the ventilatory threshold. The slope of ventilation vs. carbon dioxide output in patients with pulmonary hypertension (48 +/- 12) was steeper than the slope (31.3 +/- 7.0) in patients with normal pulmonary artery pressure (P < 0.05). Significant correlations (P < 0.05) were found between the pulmonary artery pressure and the slope of pulmonary ventilation over carbon dioxide (r = 0.92) and also with the physiological dead space-tidal volume ratio at maximal exercise (r = 0.55). This was associated with a severe reduction in exercise performance in patients with pulmonary hypertension, whereas in patients with normal pulmonary artery pressure it was only slightly below the lower limit of normal. These results demonstrate that patients with pulmonary hypertension have an inefficient ventilatory response to metabolically produced CO2 during exercise, which severely limits exercise tolerance.

Adolescent↗

[Cardiopulmonary stress test in variable frequency stimulation: a comparison of Activitrax and Nova-MR pacemakers in VVI/AAI stimulation].

In seven patients with implanted intermedics NOVA MR pacemakers, we examined the cardiopulmonary effects of maximum bicycle ergometer exercise for three types of pacing in a randomized sequence: VVI or AAI at 70/min (SSI 70), rate adaptive temperature controlled with the implanted NOVA MR, and rate adaptive activity controlled by means of a Medtronic Activitrax pacemaker taped to the chest wall, which triggered the implanted Nova MR in the VVT or AAT mode via skin electrodes. The maximum exercise tolerance was 67 W with SSI 70, 71 W with Activitrax and 91 W with Nova MR. The maximum oxygen uptake was accordingly 17.6 ml/min/kg with SSI 70, 19.5 ml/min/kg with Activitrax, and 21.5 ml/min/kg with Nova MR. The highest heart rate reached was 81 beats/min with SSI 70,98 beats/min with Activitrax and 118 beats/min with Nova MR. The rate increase from rest to maximum exercise was 11 beats/min with SSI 70,29 beats/min with Activitrax and 47 beats/min with Nova MR. An increase in exercise tolerance and maximum heart rate could be achieved with both rate adaptive types of pacing, but significantly more clearly with the temperature controlled Nova MR than with the activity controlled Activitrax. However, using a different form of exercise, e.g. treadmill ergometry, the rate response of the Activitrax would presumably have been somewhat clearer.

Aged↗

[Walking tests: a step forward for functional cardiorespiratory assessment].

Exercise testing provides information on physical capacity during exercise in addition to spirometric measures of lung function or assessment on treadmills or ergonomic cycle. The "gold standard" assessment of exercise tolerance is measured in the laboratory using treadmills or ergonomic cycle but the necessary equipment is expensive and may not be readily accessible; such tests require people used to work with children. Walking tests are field tests providing a valid and easily accessible method of measuring function-limited exercise tolerance in patients with respiratory or cardiac chronic diseases. These walking tests are non-threatening, inexpensive, easy to perform and to understand for children. Walking tests performed in daily practice are the following: "time-based" tests (2-, 6- or 12-min walking test), 3-min step test (on a step) and the shuttle walking test. It may be a useful measure to assess therapeutic intervention and provide information on the prognosis. They are simple and safe methods to evaluate quality of life in these patients.

Adolescent↗

Feasibility of a rapid diagnostic protocol for an emergency department chest pain unit.

STUDY OBJECTIVE: To evaluate the applicability of a short-stay protocol for exclusion of acute ischemic heart disease without hospital admission and to analyze these results in the context of a conceptual model. METHODS: An observational study of patients who presented with chest pain to the emergency department of an 886-bed inner-city municipal hospital and who needed hospital admission to rule out acute myocardial infarction (AMI). Patients were assessed by ED attending physicians to determine eligibility for an alternative, 12-hour protocol in an ED chest pain observation unit (CPOU) followed by immediate exercise testing. Outcome measures were proportion of patients eligible for the short-stay protocol, risk factor profile, and reasons for exclusion. RESULTS: Of 500 patients screened, 446 had sufficient data points to determine protocol eligibility. Of these, 238 (53.3%; 95% confidence interval [CI], 48.7% to 57.9%) were found to have low probability for AMI. After study exclusion criteria were applied to the patient cohort, 63 patients (14.1%; 95% CI, 10.9% to 17.3%) were eligible for the protocol. The most common reasons for exclusion were history of coronary artery disease (46%) and inability to perform an interpretable exercise tolerance test (42%). CONCLUSION: Although most admitted patients with chest pain (53%) were at low probability for AMI, only a minority (14%) were eligible for a short-stay protocol that required patients to be free of known coronary artery disease and able to perform an exercise tolerance test. Factors affecting the operations and efficiency of a CPOU include clinical characteristics of the target patient population, protocol tests used, and hospital occupancy and reimbursement patterns.

Acute Disease↗

Hemodynamic performances in patients treated with sotalol after electrical cardioversion of atrial fibrillation.

The negative inotropic effect of nearly all antiarrhythmic drugs, especially important in patients with impaired left ventricular function, represents a major drawback of medical therapy. The aim of this study is to evaluate the atrial and ventricular function and the exercise capacity in patients with mild heart failure treated with d,l-sotalol after electrical conversion of atrial fibrillation. The study included patients with persistent atrial fibrillation (for more than 2 weeks but less than 1 year) and mild heart failure (< or = class II NYHA). All patients had comparable basal echocardiographic findings, and received captopril. After successful cardioversion the patients were randomized in two groups: group 1 treated with sotalol (mean dose 240 mg q.d., max. 320 mg) and group 2--without sotalol. The drop-out criterion was the failure to maintain sinus rhythm. Finally, in the study remained 17 patients (10 men, 7 women, aged 41-60 years); group 1 included 10 patients and group 2-7 patients. They were assessed by quantitative echocardiography + Doppler and by standard ecg exercise test at less than 1 month but more than 2 weeks, and at 1, 3, and 6 months. When first evaluated (2 weeks-1 month), peak A wave velocity and atrial filling ratio were higher in group 2 than in group 1 (37 +/- 10 cm/s vs 20 +/- 5 cm/s and 23% +/- 7 vs 13% +/- 5, respectively) and group 1 had also a lower exercise tolerance (80 +/- 25 W vs 110 +/- 10 W). There were no significant differences between groups 1 and 2 in left atrial and left ventricular dimensions, ejection fraction and E wave deceleration time. After 1 month there were no significant differences in Doppler characteristics, echocardiographic parameters and exercise tolerance between the two groups. Group 1 remained at a lower heart rate and had a lower maximal double product (17250 mmHg/min vs 22100 mmHg/min) corresponding to a lower cardiac work. At 3 and 6 months there were no significant changes in all characteristics between the two groups. In conclusion, sotalol seems to be a well tolerated antiarrhythmic agent in patients with mild heart failure, after conversion of persistent atrial fibrillation. In this setting: 1. Sotalol could reversibly amplify the effect of atrial stunning after electrical cardioversion of atrial fibrillation, but this effect is brief. 2. Sotalol has no relevant negative inotropic effect, at least not in association with captopril. 3. Sotalol improves the effort capacity.

Adult↗

Individual responses to transdermal nitrates after chronic administration in angina pectoris.

The aim of this study was to investigate whether, and to which extent, sustained treatment with transdermal nitroglycerin plasters may lead to the development of tolerance in patients with effort-induced angina pectoris. Ten patients, all men, mean age 62.7 years, took part in a double-blind, cross-over, acute study, comparing the transdermal therapeutic system of nitroglycerin 10 mg/24 hours with placebo. Patients were then treated for 1 month with the active drug in single-blind condition, and finally they took part in a further acute study identical to the first. Cycloergometric exercise tests were carried out 4 hours after dosing. In comparison with placebo, the active drug significantly (P less than 0.01) increased ischaemic threshold (ST depression = 1 mm) after both acute (from 299 +- 92 to 413 +- 120 sec) and chronic treatment (416 +- 107 sec). The same results were obtained for exercise duration to peak exercise (acute study: from 336 +- 65 to 482 +- 90 sec; chronic treatment: 466 +- 118 sec). The final acute study confirmed the stability of angina, showing that the improvement in exercise tolerance after chronic treatment was entirely due to the pharmacological effect of the drug. In terms of single patient response to the active treatment, 7 of the 10 patients showed an improvement in exercise tolerance after both acute and chronic treatment, while in 3 patients no antianginal effect was observed. These results suggest that nitrate tolerance cannot be considered an inevitable finding in patients chronically treated with transdermal patches.

Administration, Cutaneous↗

Effects of oral propranolol in normal subjects.

The effects of oral propranolol were evaluated in 10 normal volunteers. The resting heart rate decreased from the mean control value of 68 plus or minus 3.3 (SE) to 56 plus or minus 2.8 beats per minute (bpm) on propranolol (p smaller than 0.001, paired test). Mean systolic blood pressur also decreased from 125 plus or minus 5.0 to 114 plus or minus 4.2 mm Hg (p smaller than 0.03). Resting systolic time intervals were unaffected by propranolol. Mean maximal treadmill exercise tolerance time was not significantly altered by propranolol although the mean heart rate systolic blood pressure product a maximal exertion was markedly decreased (1.91 plus or minus 0.17 vs 2.62 plus or minus 0.17 times 10-4, p smaller than 0.004) . The nonsignificant effect of oral propranolol on resting systolic time intervals and maximum exercise tolerance despite significant changes in heart rate and blood pressure at rest and duringexercise stand in contrast to the reported effects of intravenous propranolol. Explantations for this difference between the effects of oral and intravenous propranolol in normal subjects are examined.

Administration, Oral↗

Effects of the cardioselective beta-adrenergic receptor blocking agent metoprolol in angina pectoris. Subacute study with exercise tests.

The effect of a cardioselective beta-adrenergic blocking agent, metoprolol, on symptoms and exercise tolerance was studied in 16 patients with angina pectoris. Metroprolol was compared with placebo at two dose levels (20 mg t.d.s. and 50 mg t.d.s.) in a double-blind trial in 14 patients. Compared with placebo, metroprolol caused a significant reduction of heart rate and systolic blood pressure during exercise, and consequently a reduction of the rate-pressure product. The reduction was greater with 50 mg t.d.s. than with 20 mg t.d.s. The exercise tolerance measured as total work increased significantly by 21 per cent during treatment with metroprolol 20 mg t.d.s., and by 17 per cent during treatment with 50 mg t.d.s. There was a reduction in the number of anginal attacks and in nitroglycerin consumption, and subjective improvement of angina pectoris at both dose levels of metroprolol. No signs of cardiac failure appeared during any of the four treatment periods. Heart volume showed no significant change. Unwanted effects were of the same frequency and severity during treatment with metroprolol at both dose levels as with placebo.

Adrenergic beta-Antagonists↗

Dose related efficacy of betaxolol in combination with nitroglycerin in patients with angina pectoris: a double blind cross-over study.

The effect of three different oral doses, 5 mg, 10 mg and 20 mg of betaxolol (BTX), a new long acting cardioselective beta-adrenergic blocking drug, on exercise tolerance was studied in a randomized double blind, cross-over study with latin square distribution in nine male patients with angina pectoris, under continuous therapy with oral nitroglycerin. BTX caused a significant reduction of heart rate (p less than 0.001) for all different dose levels during exercise. Systolic blood pressure was significantly decreased at peak exercise for BTX 10 (p less than 0.01) and BTX 20 (p less than 0.001). During the three treatment periods a significant drop of the rate pressure product (p less than 0.01) was observed and a statistically significant improvement of exercise tolerance, before the occurrence of anginal pain, could be demonstrated. No differences could be detected in oxygen uptake, carbon dioxide output and ventilation between placebo- and treatment periods. BTX was well tolerated in all patients and exerted its effect also in the presence of nitroglycerin. Its cardioselectivity, ease of dosing and complete absence of side effects makes BTX an attractive choice as antianginal agent for chronic use.

Adrenergic beta-Antagonists↗

Bopindolol in chronic stable angina pectoris: duration and extent of antianginal action.

The effects of bopindolol, a new beta-adrenoceptor blocker, on the exercise tolerance of 12 in-patients, mean age 57 (5 years), with stable angina pectoris and documented coronary artery disease were evaluated. All patients received on 4 different days a single oral dose of bopindolol 0.5 mg, bopindolol 1.0 mg, bopindolol 2.0 mg and placebo according to a double-blind latin square design. Treadmill symptoms-limited exercise tests were performed using a Bruce protocol, 3, 12 and 24 h after dosing. Bipindolol improved (P less than 0.05) exercise tolerance in comparison with placebo (by a maximum of 33%, 52% and 26% after the 2.0 mg dose) with no adverse effect on ischaemia. The primary action of bopindolol appeared to be to reduce myocardial oxygen consumption (mainly by its negative chronotropic effect) for up to the 24th hour after oral administration. Eight (66%) patients were angina free at the 3rd, 12th and 24th h exercise test. The effects of bopindolol were not dose-related. A short period of inactivity due to hospitalization may have influenced the exercise performance and led us to underestimate the presence of a dose-response. The results of this report suggest that bopindolol has a long lasting effect in the treatment of patients with chronic stable angina pectoris.

Administration, Oral↗

Predictors of outcome after radiofrequency catheter ablation of the atrioventricular node for atrial fibrillation and congestive heart failure.

BACKGROUND: Although radiofrequency catheter ablation of the atrioventricular (AV) node is an established treatment for atrial fibrillation (AF) with uncontrolled ventricular response, factors that predict clinical outcome in patients with associated congestive heart failure (CHF) are unknown. METHODS AND RESULTS: AV node ablation and permanent pacemaker implantation was performed in 44 consecutive patients (mean age 71+/-10 years) with CHF and AF associated with uncontrolled ventricular response. Immediately before ablation, mean left ventricular ejection fraction (EF) measured by 2-dimensional echocardiogram was 34.6%+/-9.8%, mean exercise tolerance time was 2.6+/-1.8 minutes, and mean quality of life score was 62.3+/-19.7. Complete AV block was achieved in all 44 patients but was complicated by death in 1 patient from cardiogenic shock soon after ablation. By 1 month after ablation, EF increased to 43.8%+/-13.7% (P < .01), exercise tolerance time was 4.0+/-2.5 minutes (P < .01), and mean quality of life score decreased to 35.6+/-18.1 (P < .01). Improved cardiac performance (increase in EF > or = 9% over baseline EF) was detected in 20 (45%) of the patients. During a mean follow-up of 17+/-9 months, 5 patients died suddenly of presumed ventricular tachyarrhythmia and 4 others died of progressive CHF. Multivariate Cox survival analysis identified baseline EF < or = 30%, presence of significant mitral regurgitation (>2+) before ablation, and failure to exhibit improved cardiac performance by 1 month after ablation as the only independent predictors of death. CONCLUSIONS: Baseline variables and failure of EF to improve soon after AV node ablation identifies patients with CHF and AF who have a high mortality rate. Adjunctive therapy to reduce sudden death and progressive heart failure should be evaluated in this subgroup.

Aged↗

Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.

Adult↗

The antianginal efficacy and tolerability of controlled-release metoprolol once daily: a comparison with conventional metoprolol tablets twice daily.

In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were treated with 100 mg/day or 200 mg/day, depending on their previous beta-blocker dose. Antianginal efficacy was estimated by counting the number of anginal attacks, by noting the consumption of nitroglycerin tablets, and by exercise tolerance testing. Adverse effects were recorded by a standardized questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol CR preparation, given once daily, possesses the same antianginal efficacy as conventional metoprolol tablets, given twice daily, and may be better tolerated in patients susceptible to side-effects. The antianginal effect of metoprolol CR, 200 mg/day, may be greater over 24 h than that produced by conventional metoprolol tablets, 100 mg twice daily.

Adult↗