Efficacy Of Carvedilol In Patients Research Articles

Association of common polymorphisms in β1-adrenergic receptor with antihypertensive response to carvedilol.

Marked interpatient variability exists in the blood pressure response to carvedilol, a nonselective β-blocker. Here we evaluated the influence of 4 common polymorphisms in genes of the β-adrenergic receptor on the antihypertensive efficacy of carvedilol in patients in a double-blinded monotherapy study. Eighty-seven subjects with uncomplicated essential hypertensive (49% men; age = 52.2 ± 11.1 years) from Jilin province of China were enrolled in the study, and 5 of them discontinued the treatment due to adverse effects. Both systolic and diastolic blood pressures (DBPs) were measured before and after 7 days of treatment with carvedilol (10 mg/d). Genotypes of the β1-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly) and β2-adrenergic receptor (ADRB2 Gly16Arg and Glu27Gln) were determined by polymerase chain reaction with restriction fragment length polymorphism. Patients homozygous for ADRB1 Arg389 had an approximately 4-fold greater reduction in DBPs than those homozygous for ADRB1 Gly389 (10.61 vs. 2.62 mm Hg, P = 0.013). The ADRB1 haplotype was also a significant predictor of response, as patients with the Gly49Arg389/Ser49Arg389 haplotype pair had a 5.7-fold greater reduction in DBPs than those homozygous for the Ser49Gly389 haplotype (16.11 vs. 2.83 mm Hg, P = 0.0055). An association was not found between ADRB2 polymorphism and carvedilol responsiveness in antihypertensive therapy. This study provides the first evidence to support that ADRB1 polymorphisms play an important role in the DBPs response to carvedilol treatment in patients with essential hypertension.

Tolerability of carvedilol in patients with heart failure and concomitant chronic obstructive pulmonary disease or asthma

Background A substantial proportion of the population with congestive heart failure (CHF) has concomitant airway disease. Little information exists on the tolerability of carvedilol in patients with chronic obstructive pulmonary disease (COPD). In this study, we assessed the tolerability and efficacy of carvedilol in patients with CHF and concomitant COPD or asthma. Methods Between 1996 and 2000, a total of 487 patients began receiving open-label carvedilol. Forty-three (9%) had COPD ( n = 31) or asthma ( n = 12). Spirometry supported clinical diagnosis in all, and full pulmonary function testing supported diagnosis in 71%. Sixty percent began carvedilol therapy in the hospital and underwent measurement of peak expiratory flow rates (PEFR) before and after dosing. Results In patients with COPD, mean forced expiratory volume in one second (FEV 1) was 62% ± 13% predicted, reversibility was 4% ± 4% with bronchodilators, and FEV 1/FVC was 62% ± 8%. Mean PEFR was 325 ± 115 liter/min before the dose and increased by 17% 2 hours after the carvedilol dose ( p = 0.04). In patients with asthma, mean FEV 1 was 80% ± 17% predicted, reversibility was 13% ± 7% , and FEV 1/FVC was 74% ± 11%. Mean PEFR was 407 ± 161 liter/min before the dose with no significant change 2 hours after the dose. Carvedilol was introduced safely in 84% of patients with COPD, with only 1 patient withdrawn from therapy for wheezing. In contrast, only 50% of patients with asthma tolerated carvedilol. Survival at 2.5 years was 72%. In survivors, left ventricular end-diastolic diameter decreased from 76 ± 11 mm to 72 ± 14 mm ( p = 0.01), left ventricular end-systolic diameter decreased from 65 ± 13 mm to 60 ± 15 mm ( p = 0.01), and fractional shortening increased from 14% ± 7% to 17% ± 7% ( p = 0.05) at 12 months. Conclusions Patients with CHF and COPD tolerated carvedilol well with no significant reversible airflow limitation, but patients with CHF and asthma tolerated carvedilol poorly. The effect of carvedilol on left ventricular dimensions and function in patients with concomitant airway diseases was similar to that seen in our general group of patients. Asthma remains a contraindication to β-blockade.

Impact of concurrent amiodarone treatment on the tolerability and efficacy of carvedilol in patients with chronic heart failure

OBJECTIVETo assess the safety and efficacy of carvedilol when administered to heart failure patients already receiving amiodarone.DESIGNRetrospective analysis of the clinical outcome of 230 patients treated with carvedilol for chronic...

Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure

OBJECTIVESThe purpose of this study was to assess the tolerability and efficacy of carvedilol in patients with New York Heart Association (NYHA) functional class IV symptoms.BACKGROUNDCarvedilol, a nonselective beta-adrenergic blocking drug with alpha-adrenergic blocking and antioxidant properties, has been shown to improve left ventricular function and clinical outcome in patients with mild to moderate chronic heart failure.METHODSWe retrospectively analyzed the outcomes of 230 patients with heart failure treated with carvedilol who were stratified according to baseline functional class: 63 patients were NYHA class IV and 167 were NYHA class I, II or III. Carvedilol was commenced at 3.125 mg b.i.d. and titrated to 25 mg b.i.d. as tolerated. Patients with class IV symptoms were older (p = 0.03), had lower left ventricular fractional shortening (p < 0.001), had lower six-min walk distance (p < 0.001) and were receiving more heart failure medications at baseline compared with less symptomatic patients.RESULTSNonfatal adverse events while taking carvedilol occurred more frequently in class IV patients (43% vs. 24%, p < 0.0001), and more often resulted in permanent withdrawal of the drug (25% vs. 13%, p < 0.01). Thirty-seven (59%) patients who were NYHA class IV at baseline had improved by one or more functional class at 3 months, 8 (13%) were unchanged and 18 (29%) had deteriorated or died. Among the less symptomatic group, 62 (37%) patients had improved their NYHA status at 3 months, 73 (44%) were unchanged and 32 (19%) had deteriorated or died. The differences in symptomatic outcome at three months between the two groups were statistically significant (p = 0.001, chi-square analysis). Both groups demonstrated similar significant improvements in left ventricular dimensions and systolic function.CONCLUSIONSPatients with chronic NYHA class IV heart failure are more likely to develop adverse events during initiation and dose titration when compared with less symptomatic patients but are more likely to show symptomatic improvement in the long term. We conclude that carvedilol is a useful adjunctive therapy for patients with NYHA class IV heart failure; however, they require close observation during initiation and titration of the drug.

Clinical Efficacy of Carvedilol in Patients with Moderate to Severe Congestive Heart Failure

Background：Clinical trials have shown that β-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate congestive heart failure. Carvedilol is a mild β1-selective adrenergic blocking agent with vasodilating properties due to α blocker and antioxidant and anti-proliferative properties. This study assessed the efficacy and safety of carvedilol in patients with moderate to severe congestive heart failure caused by idiopathic dilated cardiomyopathy. Methods：We enrolled 27 patients with moderate to severe congestive heart failure with a left ventricular ejection fraction of 35% by MUGA scan. Each patient was randomly assigned to either control (n＝9 or carvedilol (n＝18, target dose 25 mg bid for 6 months while background therapy with digoxin, diuretics, and ACE inhibitor remained constant. Results：Compared to the control group, patients in the carvedilol group showed significant increase of left ventricular ejection fraction (p<0.05. In addition, patients in the carvedilol group had a tendency to show a decrease in left ventricular end-diastolic dimension and heart rate. Also, the carvedilol group had a greater frequency of symptomatic improvement than the control group. There was neither serious side effects nor hospitalization. Conclusion： These finding indicate that carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and ACE inhibitor without serious side effects. (Korean Circulation J 1998;28(4 :523-531

Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders.

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.

Carvedilol improves left ventricular function and symptoms in chronic heart failure: A double-blind randomized study

This study assessed the safety and efficacy of carvedilol in patients with heart failure caused by idiopathic or ischemic cardiomyopathy. Carvedilol is a mildly beta 1-selective beta-adrenergic blocking agent with vasodilator properties. Beta-blockade may be beneficial in patients with heart failure, but the effects of carvedilol are not known. Sixty patients with heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction < or = 0.35 were enrolled in the study. All patients tolerated challenge with carvedilol, 3.125 mg twice a day, and were randomized to receive carvedilol (n = 36) versus placebo (n = 24). Study medication was titrated over 1 month from 6.25 to 25 mg twice a day (< 75 kg) or 50 mg twice a day (> 75 kg) and continued for 3 months. One placebo-treated and two carvedilol-treated patients did not complete the study. Carvedilol therapy resulted in a significant reduction in heart rate and mean pulmonary artery and pulmonary capillary wedge pressures and a significant increase in stroke volume and left ventricular stroke work. Left ventricular ejection fraction increased 52% in the carvedilol group (from 0.21 to 0.32, p < 0.0001 vs. placebo group). Carvedilol-treated patients also reported a significant lessening of heart failure symptoms (p < 0.05 vs. placebo group). Submaximal exercise duration tended to increase with carvedilol therapy (from 688 +/- 31 s to 871 +/- 32 s), but this change was not significantly different from that with placebo therapy by between-group analysis. Peak oxygen consumption during maximal exercise did not change. Long-term carvedilol therapy improves rest cardiac function and lessens symptoms in patients with heart failure.

Efficacy of carvedilol in hypertensive black patients: A pilot study

Beta-blockers do not effectively control blood pressure in hypertensive black patients. Carvedilol is a new, noncardioselective, vasodilating beta-adrenoceptor blocker without intrinsic sympathomimetic activity. The efficacy of carvedilol in patients with mild-to-moderate hypertension has been proven in whites but not in blacks. In a single-blind study, we evaluated the blood-pressure-lowering effect of carvedilol 25 mg once daily for 4 weeks in 20 black patients. Patients previously treated with antihypertensive medication completed a 2-week washout period before receiving carvedilol. Patients who responded to treatment with carvedilol 25 mg once daily continued to receive the drug for an additional 4 weeks. Nonresponders received carvedilol 25 mg plus hydrochlorothiazide 25 mg once daily for a further 4 weeks. The baseline sitting blood pressure after placebo was 168.2 ± 12.6 mmHg systolic and 100.9 ± 3.5 mmHg. After 4 weeks, sitting blood pressure decreased to 157.5 ± 19.3 mmHg systolic and 88.4 ± 8.3 mmHg diastolic ( P < 0.001). At the end of 8 weeks, the sitting systolic blood pressure was 155.8 ± 12.9 mmHg and the diastolic blood pressure was 84.2 mmHg ± 6.3 mmHg ( P < 0.001). Heart rate decreased from 74.3 ± 11.9 beats/min to 65.4 ± 9.8 beats/min at the end of 8 weeks. Seventeen (85%) patients responded to carvedilol 25 mg daily and 3 (15%) patients responded to carvedilol 25 mg daily combined with hydrochlorothiazide. Carvedilol is an effective agent for treating hypertension in black patients.