Regression of left ventricular remodeling in chronic heart failure: Comparative and combined effects of captopril and carvedilol.

BACKGROUND: This study evaluated the independent and combined effects of captopril and carvedilol on left ventricular remodeling in chronic heart failure. Although angiotensin-converting enzyme inhibitors and b-blockers are known to attenuate the remodeling process in chronic heart failure, a direct comparison of these agents has not been performed. METHODS: We investigated 57 patients with mild to moderate chronic heart failure (48 ischemic, 9 nonischemic) who were randomized in a double-blind fashion to treatment with carvedilol or captopril at maximum doses of 25 mg twice daily for 3 months, followed by 3 months of combined treatment. Serial echocardiography, right heart catheterization, and treadmill exercise testing were performed at baseline, 3 months, and 6 months. After exclusions, 49 patients were evaluated during monotherapy and 48 during combination therapy. RESULTS: Carvedilol monotherapy produced significant reductions in end-systolic volume, leading to a greater median increase in ejection fraction compared with captopril monotherapy (4.7% vs 1.5%, respectively; P <.05). Each drug caused similar reductions in left ventricular mass, chamber sphericity, and pulmonary artery wedge pressure during monotherapy and combined treatment. Adjunctive treatment with carvedilol produced a trend toward a greater increase in ejection fraction (4.3% vs 2.7%, respectively; P not significant) and significantly greater reductions in the wall thickening score index than with captopril (0.25 vs 0.08, respectively; P =.04). CONCLUSIONS: Although angiotensin-converting enzyme inhibitor therapy did not alter left ventricular volume, treatment with carvedilol was associated with reductions in chamber volume; both drugs reduced left ventricular mass and sphericity. These beneficial effects on remodeling may help to explain the relative prognostic benefits of these therapies.

A randomized, double-blind, parallel-group study to compare the anti-hypertensive effects of imidapril and nifedipine in the treatment of mild-to-moderate essential hypertension.

This 12-week, multicentre, double-blind, placebo-controlled, parallel-group study compared efficacy of the angiotensin-converting enzyme (ACE) inhibitor imidapril 5 - 10 mg/day and the calcium channel blocker nifedipine slow-release (SR) formulation 20 - 40 mg twice daily. In total 320 patients aged 18 - 75 years, with mean sitting diastolic blood pressures of 95 - 115 mmHg, were randomized to treatment with imidapril (n = 157) or nifedipine SR (n = 163). Efficacy evaluations were based on the intent-to-treat principle. On study completion, there was no difference between the groups with respect to the primary efficacy variable of response to treatment (imidapril 63.1%; nifedipine SR 61.3%). After 2 weeks' treatment, clinically relevant decreases in blood pressure were observed in both groups, with a trend towards further reductions until study end. Fewer patients in the imidapril-treated group than the nifedipine group withdrew due to adverse events that occurred on treatment with study medication (3.2% versus 16.0%) or experienced adverse events (40.1% versus 49.7%). In addition, fewer adverse events were causally related to imidapril (24.2%) compared with nifedipine SR (41.7%). These results show that imidapril is effective in the treatment of essential hypertension and is better tolerated than nifedipine SR.

Comparison of safety and efficacy of carvedilol and metoprolol in stable angina pectoris.

In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 to 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was < 1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no hitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol's vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients > or = 65 years of age. However, in the doses selected, which appeared equipotent with respect to beta blockade, carvedilol's improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses.

Hemodynamic differences between metoprolol and carvedilol in hypertensive patients.

Resting hemodynamics were measured before, at 2 and 24 h after the first dose, and after 4 weeks of monotherapy with either metoprolol or carvedilol in a randomized single-blind study. We analyzed results from 24 hypertensive patients (30-68 years of age) with adequate blood-pressure lowering on monotherapy. Acutely, both drugs lowered systolic blood pressure and heart rate. Whereas metoprolol reduced cardiac output and increased both systemic and femoral artery resistance, carvedilol did not alter cardiac output but led to reductions in the systemic and regional resistances. After 4 weeks of therapy, cardiac output remained reduced and vascular resistances increased in the metoprolol group, whereas in carvedilol patients cardiac output continued to be unchanged and the trend for vascular resistances to be decreased persisted. Acutely and chronically the differences in the hemodynamic effects of the two medications were statistically significant. The study results indicate that carvedilol's vasodilatory action is not subject to tolerance development. Chronic afterload reduction associated with the decrease in systemic vascular resistance may lead to additional savings in myocardial oxygen consumption, a beneficial feature particularly in those patients with concomitant ischemic heart disease. It may also have a favorable influence on concentric cardiac hypertrophy and changes in the walls of arteriolar resistance vessels.

Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial.

BACKGROUND: Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS: This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS: Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.

Comparison of the hemodynamic effects of metoprolol and carvedilol in hypertensive patients.

Metoprolol and carvedilol are widely used in the treatment of hypertension, but no randomized comparison of their hemodynamic activity has been previously reported. Their comparative effects on heart rate, systemic blood pressure, and echocardiographically determined aortic and femoral artery blood flow were measured at rest and at 2 and 24 hours after the first dose of each drug, and again after 4 weeks of sustained monotherapy in 12 male and 12 female patients, aged 36-68 years with uncomplicated sustained hypertension according to a randomized single-blind protocol. Nine patients in each drug group achieved the target diastolic blood pressure of < 90 mmHg on the initial doses of each drug; this was achieved in the remainder following doubling of each dose. Neither drug occasioned withdrawal of any patient due to adverse reactions. Both drugs significantly reduced heart rate, although the reduction at 2 hours was significantly greater after metoprolol than after carvedilol. Both drugs reduced systolic pressure throughout the study; the reduction at 2 hours was significantly greater after carvedilol than after metoprolol. In contrast, the diastolic blood pressure was persistently reduced only by carvedilol. The cardiac output, determined as the aortic systolic blood flow, after carvedilol was not significantly different from pretreatment values throughout the study but was significantly reduced in the metoprolol-treated patients at each point of measurement. After metoprolol the systemic and femoral vascular resistances derived from conventional formulae were consistently and significantly increased over pretreatment values throughout the study and were significantly greater than in the carvedilol group at all measurement points. The hemodynamic differences between these two beta-blocking drugs may be explained by the additional vasodilator activity of carvedilol associated with its alpha 1-adrenoceptor blocking activity. The long-term clinical and prognostic implications of these pharmacodynamic differences between beta-adrenoceptor antagonists with and without additional vasodilator activity in the treatment of hypertensive patients remain to be determined.

A comparison of carvedilol with a combination of propranolol and isosorbide dinitrate in the chronic treatment of stable angina.

The beta-blocking and vasodilating agent carvedilol was compared with a combination of propranolol and isosorbide dinitrate (ISDN) in a double-blind, parallel-group study. After two baseline sitting bicycle exercise tests on placebo, 31 patients with chronic stable angina were asymmetrically randomized to treatment with carvedilol (25 mg b.i.d.) or propranolol-ISDN (80 mg/20 mg b.i.d.) for a period of 6 months. Further exercise tests were performed 2 h after the first dose as well as after 1, 3, and 6 months of treatment. Twenty-seven patients were considered evaluable for efficacy. Differences between the two groups were observed with emphasis on total exercise time and time to 1-mm ST-segment depression. In contrast to a greater peak effect of the first propranolol/ISDN dose, the chronic antianginal and anti-ischemic effects of carvedilol at trough were found to be more marked than those of the combination.

Effects of carvedilol on ventricular arrhythmias.

Carvedilol is a nonselective beta-blocker with alpha-mediated vasodilating properties that has been shown to be effective in systemic hypertension, stable angina, and congestive heart failure (CHF). In this study, we studied the effects of carvedilol on premature ventricular contractions (PVCs) in 65 patients undergoing treatment with carvedilol (12.5-50 mg b.i.d.) for 4-8 weeks. Twelve patients had hypertension, 41 had stable angina, and 12 had CHF. Holter monitoring for 24 h was performed before and after active carvedilol therapy. Median PVCs per 24 h decreased from 25.5 to 6.0 (p less than 0.001, n = 52). Reduction in PVC activity occurred in 77% of patients, and 23% of patients with multifocal PVCs changed their morphology to unifocal. Nonsustained ventricular tachycardia was present in four patients before treatment; this was abolished in all patients. R-on-T PVC was present in six patients; it decreased in five and increased in one. New ventricular tachycardia (less than 8 beats) occurred in two patients, but QT prolongation was not noted in these patients. An improvement in Lown's classification occurred in 50% of patients. However, in the CHF group, the improvement in Lown's criteria was observed in 73% of patients. Carvedilol does not appear to possess proarrhythmic effects, and chronic therapy reduces PVC activity in a wide range of patients. This property of carvedilol is complementary to its hypotensive and anti-ischemic effects. In the CHF group, the beneficial effects of carvedilol on left ventricular function and hemodynamics may combine with the improvement in PVC activity to produce a significant improvement in mortality.

Efficacy and safety of carvedilol in comparison with nifedipine sustained-release in chronic stable angina.

In patients with chronic stable exertional angina pectoris, the antianginal and anti-ischemic efficacies and the safety of 25 mg carvedilol b.i.d. were compared with those of 20 mg nifedipine sustained-release (SR) in a double-blind, randomized, multicenter study. In 22 centers, 166 patients were enrolled. After washout and run-in phases with two symptom-limited seated bicycle exercise tests on placebo, eligible patients were allocated to one of the two parallel treatment groups. After 4 weeks of active treatment, an additional exercise test was performed 12 h after the preceding dose. The patients were issued diary cards to document the daily number of anginal attacks and glyceryl trinitrate applications. Symptom-limited total exercise time, time to onset of angina, and time to 1-mm ST-segment depression increased with both treatments vs. placebo baseline values. The changes were more distinct in the carvedilol group, but the between-group differences were not statistically significant. Angina symptomatology during daily life and glyceryl trinitrate consumption were markedly improved by each treatment. Adverse events on treatment, particularly those correlated to vasodilation, were less frequent in the carvedilol group.

Treatment of chronic stable angina with carvedilol in comparison with nifedipine s.r.

Carvedilol 25 mg b.d. was compared with nifedipine s.r. 20 mg b.d. for subchronic treatment of patients with chronic stable angina. After washout and placebo run-in, 163 patients were randomly and double-blindly allocated to one of the two treatment groups. Two symptom-limited seated bicycle exercise tests were performed on placebo in order to confirm stable baseline conditions. After 4 weeks of active treatment, a further exercise test was performed in the morning, 12 h after the preceding dose. Diary cards were kept by the patients throughout the trial in order to record angina attacks and glyceryl trinitrate consumption. Carvedilol seemed to be somewhat more effective than nifedipine s.r. for improving exercise tolerance and exercise time to onset of angina and 1 mm ST-segment depression. Although there were highly statistically significant differences vs placebo, the two treatment groups did not differ significantly. No difference between treatment with carvedilol and nifedipine s.r. was found regarding angina symptoms and glyceryl trinitrate consumption during daily life. Adverse events were less frequently reported in the carvedilol group than in the nifedipine group. Generally, however, both agents were well tolerated. Carvedilol therapy for chronic stable angina seems to be both efficacious and safe.

[Neither propranolol nor the vasodilating beta-blocker carvedilol have a direct effect on coronary resistance vessels]. / Weder Propranolol noch der vasodilatierende beta-Blocker Carvedilol besitzen eine direkte Wirkung auf die koronaren Widerstandsgefässe.

Seventeen patients with coronary heart disease were included in a double-blind randomized study. They received either 5 mg of carvedilol or 6 mg of propranolol intravenously. Heart rate, aortic pressure, mean coronary sinus pressure and coronary flow (thermodilution) were measured, and coronary resistance and rate-pressure product were calculated before and 15 min after the infusion, which lasted 10 min. Carvedilol lowered significantly (p less than 0.05) heart rate (mean 76 to 69/min), aortic pressure (mean 153/80 to 135/72 mm Hg), rate-pressure product (mean 117 to 93 mm Hg/min) and coronary flow (mean 114 to 94 ml/min). Coronary resistance and coronary flow related to rate-pressure product showed no significant change after carvedilol. Propranolol lowered heart rate (mean 76 to 64/min; p less than 0.05) and rate-pressure product (mean 109 to 96 mm Hg/min; ns). Aortic pressure, coronary flow, coronary resistance, and coronary flow related to rate-pressure product showed no significant change after propranolol. Thus, carvedilol lowered rate-pressure product more markedly than propranolol on account of its acute blood-pressure lowering effect. Neither drug seems to have a direct influence on coronary resistance vessels.

[Acute hemodynamic effects of the vasodilator beta blocker carvedilol in heart failure]. / Akute hämodynamische Effekte des vasodilatierenden Betablockers Carvedilol bei Herzinsuffizienz.

The beta-blocker carvedilol has been shown to induce vasodilation in patients with coronary artery disease. In a double-blind, randomized, placebo-controlled cross-over study, we looked for the acute vasodilating effect after i.v. administration in patients with heart failure. In 10 patients with coronary artery disease and six patients with dilated cardiomyopathy, all with an ejection fraction lower than 40%, the rate-pressure-product during supine ergometry and Swan-Ganz-catheterization rose to a significantly smaller extent after 5 mg carvedilol i.v. compared to placebo. This was mainly due to a lower heart rate at rest and during exercise, while blood pressure was not changed compared to placebo. Calculated total peripheral resistance during exercise after carvedilol was higher--significantly so in the CAD-group--than after placebo. These results show that in patients with heart failure, an acute vasodilating effect of i.v. carvedilol is not detectable.

Influence of carvedilol and propranolol on coronary blood flow.

A total of 17 patients with angiographically proven coronary artery disease and at least one stenosis blocking greater than or equal to 70% of the left anterior descending or circumflex artery were included in a double-blind, randomized study. They received either 5 mg carvedilol or 6 mg propranolol intravenously. Heart rate, aortic pressure, mean coronary sinus pressure and coronary flow (thermodilution) were measured and coronary resistance and the rate-pressure product were calculated before and 25 min after injection. Carvedilol significantly (P less than 0.05) lowered the heart rate (mean, 76 to 69 beats/min), aortic pressure (mean, 153/80-135/72 mm Hg), rate-pressure product (mean, 117-93 mm Hg/min), and coronary flow (mean, 114-94 ml/min). Coronary resistance (mean, 0.97-1.07 mm Hg x min/ml) and coronary flow related to the rate-pressure product (mean, 1.0-1.02 ml/mm Hg) showed no significant change after carvedilol treatment. Propranolol lowered the heart rate (mean, 76-64/min; P less than 0.05) and rate-pressure product (mean, 109-96 mm Hg/min; not significant). Aortic pressure (mean, 145/72-147/74 mm Hg), coronary flow (mean 109-101 ml/min), coronary resistance (mean, 1.1-1.2 mm Hg x min/ml), and coronary flow related to the rate-pressure product (mean, 1.12-1.19 ml/mm Hg) showed no significant change after propranolol administration. Following single application, carvedilol lowered the rate-pressure product more markedly than did propranolol on account of its acute blood-pressure-lowering effect. No differences in the hemodynamic effects of carvedilol and propranolol were found. Neither drug seems to influence the adaption of coronary flow to myocardial oxygen demand.

Safety and antihypertensive efficacy of carvedilol and atenolol alone and in combination with hydrochlorothiazide.

Carvedilol has been shown to be effective and safe in patients with essential hypertension when given as monotherapy. In this double-blind, randomized, group-comparative study, 2 groups of 59 patients with mild to moderate essential hypertension [median supine systolic/diastolic blood pressure at baseline (SBP/DBP), 168/105 mmHg] were treated with either 25 mg carvedilol once daily (o.d.) or 50 mg atenolol o.d. for 4 weeks. Responders at 4 weeks (DBP, less than 90 mmHg) terminated the study. Nonresponders continued the study. Hydrochlorothiazide (HCTZ) was added at 25 mg o.d. for a further 6 weeks. The median blood pressure decreased under monotherapy with carvedilol (n = 59) from 167/105 at baseline to 155/94 mmHg after 4 weeks, and in the atenolol group (n = 59) it decreased from 168/105 to 162/97 mmHg. The patients who received carvedilol in combination with HCTZ and were evaluated for efficacy (n = 38) showed a decrease in SBP/DBP from 156/97 at the end of monotherapy to 145/88 mmHg after 10 weeks; the combination of atenolol with HCTZ (n = 44) reduced BP from 162/97 to 147/88. Both carvedilol and atenolol were safe when given either alone or in combination with HCTZ. In conclusion, after long-term administration, 25 mg carvedilol o.d. and 50 mg atenolol o.d. significantly reduced both SBP and DBP over 24 h. The addition of HCTZ led to a further increase in antihypertensive efficacy. Combined treatment with carvedilol or atenolol and HCTZ was very well tolerated, without hypotensive events or relevant changes in objective safety parameters.

Efficacy and safety of carvedilol in comparison with atenolol in hypertensive patients pretreated with hydrochlorothiazide.

Carvedilol [25 mg once daily] (o.d.) was compared to atenolol (50 mg o.d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP), 100-115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o.d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group, n = 54; A/HCTZ group, n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of less than 90 mm Hg. In a relatively low number of patients (6 of 131), a response as defined above was achieved with HCTZ alone. This may be accounted for by the fact that patients were required to have a diastolic blood pressure of at least 100 mg Hg and by the relatively short period of monotherapy. The two groups of patients receiving different combination treatments were well matched for demographic data and blood pressure values before the adjunct was added. In both groups there was a marked additional blood pressure decrease on the initiation of combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of carvedilol in patients with impaired left ventricular function due to ischaemic heart disease.

In this single-blind, placebo-controlled trial, carvedilol, a nonselective beta-blocking and vasodilating agent was studied in six patients with chronic stable angina. All patients had reproducible treadmill exercise time without medical treatment and developed chest pain in association with ST-segment depression (greater than 1 mm at J + 80 msec) on exercise. None had a history of rest or unstable angina or myocardial infarction within three months prior to the study. In all patients, anti-anginal medication except sublingual nitroglycerin was discontinued for 10 days. The patients entered an initial two week-phase of placebo. They then received carvedilol, 25 mg and then 50 mg twice daily for two weeks on each dose, followed by another two week-placebo-phase. Radionuclide ventriculography was performed at the end of each phase at rest and during maximal symptom-limited exercise. Bicycle ergometry was carried out in the supine position with incremental workloads. Exercise time and workload were recorded at the end of the first phase and imaging was performed at the same time and workload throughout the trial. Carvedilol produced a dose-related reduction in rest and exercise heart rate and blood pressure. Peak exercise ST-segment change was reduced by both doses of carvedilol, but this did not achieve a level of significance. After the first placebo phase all patients had abnormal left ventricular wall motion and resting ejection fraction (range: 35% to 45%). Four out of six patients had significant improvement in wall motion abnormalities, in two patients there was no change, and none developed a deterioration in abnormal wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of carvedilol on blood glucose and glycohaemoglobin A1 in non-insulin-dependent diabetics.

Pharmacological treatment of hypertension can, cause clinically significant alterations in endocrine function and glucose homeostasis. The aim of this study was to investigate the antihypertensive efficacy and the influence on carbohydrate metabolism of carvedilol and metoprolol in non-insulin-dependent diabetics with mild to moderate hypertension. The patients received either carvedilol 25mg twice daily or metoprolol 50mg twice daily for a period of 4 weeks; if diastolic blood pressure was over 90mm Hg at this time, the dosage was doubled for the subsequent 4 weeks. 49 of 89 enrolled patients completed the trial according to the protocol and were statistically evaluated. After 4 weeks of carvedilol treatment, 23 of 25 patients (92%) showed a good response to therapy (reduction of diastolic blood pressure below 90mm Hg). Doubling of dosage in the carvedilol group did not further increase the response rate after another month of treatment. The response rate after 4 and 8 weeks of metroprolol treatment was 79 and 83%, respectively. In both treatment groups, blood glucose concentrations were maintained within narrow limits. Glycated haemoglobin A1, which provides a profile of the mean blood glucose levels present during the preceding weeks, also remained unchanged. Oral antidiabetic medication taken by the patient remained constant and no hypoglycaemia was reported. When used in therapeutic doses in non-insulin-dependent diabetics, carvedilol is thus unlikely to cause a deterioration of carbohydrate metabolism.

Acute hemodynamic effects of the vasodilating and beta-blocking agent carvedilol in comparison to propranolol.

In a randomized double-blind study, oral doses of 50 mg carvedilol were compared to 40 mg propranolol in 16 male patients with coronary heart disease (12 without significant stenosis after percutaneous transluminal coronary angioplasty) at rest, during and after exercise, and before and 80 min after drug application. Systemic and pulmonary pressures, heart rate, cardiac index, and lower limb blood flow were measured, and systemic and pulmonary resistances calculated. Carvedilol does not lead, as the classical beta-blocker propranolol does, to an increase in systemic or pulmonary resistance, nor to a decrease in cardiac output, or to an increase of the pulmonary capillary wedge pressure during exercise. In contrast to propranolol, the postexercise lower limb blood flow has increased significantly. The differences in action between the two beta-blockers can be explained by the vasodilating properties of carvedilol. Due to these acute effects, carvedilol may be of advantage compared to propranolol in the treatment of peripheral occlusive artery disease, hypertension, and coronary vasospasm.