Carvedilol Therapy In Patients Research Articles

Effects of Long-Term Carvedilol Therapy in Patients With ST-Segment Elevation Myocardial Infarction and Mildly Reduced Left Ventricular Ejection Fraction

The benefits of long-term oral β-blocker therapy in patients with ST-segment elevation myocardial infarction (STEMI) with mildly reduced left ventricular ejection fraction (LVEF; ≥40%) are still unknown. We sought to evaluate the efficacy of β-blocker therapy in patients with STEMI with mildly reduced LVEF. In the CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-Scale Randomized Controlled Trial), patients with STEMI with successful percutaneous coronary intervention with an LVEF of ≥40% were randomly assigned to carvedilol or no β-blocker therapy. Among 794 patients, 280 patients had an LVEF of <55% at baseline (mildly reduced LVEF stratum), whereas 514 patients had an LVEF of ≥55% at baseline (normal LVEF stratum). The primary end point was a composite of all-cause death, myocardial infarction, hospitalization for acute coronary syndrome, and hospitalization for heart failure, and the secondary end point was a cardiac composite outcome: a composite of cardiac death, myocardial infarction, and hospitalization for heart failure. The median follow-up period was 3.7years. The lower risk of carvedilol therapy relative to no β-blocker therapy was not significant for the primary end point in either the mildly reduced or normal LVEF strata. However, it was significant for the cardiac composite end point in the mildly reduced LVEF stratum (0.82/100 person-years vs 2.59/100 person-years, hazard ratio 0.32 [0.10 to 0.99], p=0.047) but not in the normal LVEF stratum (1.48/100 person-years vs 1.06/100 person-years, hazard ratio 1.39 [0.62 to 3.13], p=0.43, p for interaction=0.04). In conclusion, long-term carvedilol therapy in patients with STEMI with primary percutaneous coronary intervention might be beneficial for preventing cardiac-related events in those with a mildly reduced LVEF.

Therapeutic Inefficacy and Proarrhythmic Nature of Metoprolol Succinate and Carvedilol Therapy in Patients With Idiopathic, Frequent, Monomorphic Premature Ventricular Contractions.

Antiarrhythmic drugs remain the first-line therapy for treatment of idiopathic ventricular arrhythmias. The aim of this study was to assess the therapeutic efficacy of extended-release metoprolol succinate (MetS) and carvedilol for idiopathic, frequent, monomorphic premature ventricular contractions (PVCs). Study population consisted of 114 consecutive patients: 71 received MetS and 43 received carvedilol. All patients underwent 24-hour Holter monitoring at baseline and during drug therapy. PVC-burden response to drug therapy was categorized as "good" (≥80% reduction), "poor" (either <80% reduction or ≤50% increase), and "proarrhythmic" responses (>50% increase) based on change in PVC burden compared with baseline. Most common presenting symptom was palpitations (65.8%), followed by coincidental discovery (29%). The mean MetS and carvedilol dosages were 65.57 ± 30.67 mg/d and 23.66 ± 4.26 mg/d, respectively. "Good," "poor," and "proarrhythmic" responses were observed in 11.3% and 16.3%, 63.4% and 67.4%, and 25.3% and 16.3% of patients treated with MetS and carvedilol, respectively. In patients with relatively high (≥16%) PVC burden, the sum of "poor"/"proarrhythmic" response was observed in 95.5% and 86.4% of patients treated with MetS and carvedilol, respectively. "Proarrhythmic" response was observed in 21.9% of the patients, particularly in the presence of relatively lower (≤10%) baseline PVC burden. Patients with "good" response during beta-blocker therapy had higher baseline daily average intrinsic total heart beats compared with patients with "poor"/"proarrhythmic" response combined (96,437 ± 26,488 vs. 86,635 ± 15,028, P = 0.047, respectively). Side effects and intolerance were observed in 5.6% and 18.6% of patients treated with MetS and carvedilol, respectively. MetS and carvedilol for idiopathic, frequent, monomorphic PVCs are frequently inefficient. Therapeutic efficacy decreases further in patients with relatively high (≥16%) PVC burden. Relatively higher baseline daily intrinsic total heart beats may be used to predict "good" response before beta-blocker therapy.

P351Therapeutic inefficacy and pro-arrhythmic nature of metoprolol succinate and carvedilol therapy in patients with idiopathic, frequent, monomorphic premature ventricular contractions

Abstract Funding Acknowledgements None Background Anti-arrhythmic drugs remain the first-line therapy for treatment of idiopathic ventricular arrhythmias in clinical practice. Purpose The aim of this study was to assess the therapeutic efficacy of extended-release metoprolol succinate (MetS) and carvedilol for idiopathic, frequent, monomorphic premature ventricular contractions (PVCs). Methods Study population consisted of 115 consecutive patients: 72 received MetS and 43 received carvedilol. All patients underwent 24-hour Holter monitoring at baseline and during drug therapy. PVC burden response to drug therapy was categorized as "Good" (≥80% reduction), "Poor" (either &amp;lt; 80% reduction or ≤ 50% increase) and "Pro-arrhythmic" response (&amp;gt; 50% increase) based on change in PVC burden compared to baseline. Results Presenting symptoms were palpitations in 69 (60%), shortness of breath/chest pain/syncope in 12 (10.5%), and coincidentally discovered in 34 (29.5%) patients. Mean MetS and carvedilol dosages were 65.57 ± 30.67 mg/day and 23.66 ± 4.26 mg/day, respectively. "Good", "Poor" and "Pro-arrhythmic" response was observed in 13.9% and 23.3%, 61.1% and 60.5%, and 25% and 16.2% of patients treated with MetS and carvedilol, respectively. In patients with relatively high (≥16%) PVC burden, "Poor" response was observed in 86.9% and 76% of patients treated with MetS and carvedilol, respectively. Side-effects and/or intolerance were observed in 5.5 % and 13.9 % of patients treated with MetS and carvedilol, respectively. Conclusions MetS and carvedilol for idiopathic, frequent, monomorphic PVCs is frequently inefficient. Therapeutic efficacy decreases further in patients with relatively high (≥16%) PVC burden. "Pro-arrhythmic" response was observed in approximately one quarter of the patients. All patients Metoprolol Succinate (n = 71) Carvedilol (n = 43) p value Good response,n (%) 7 (9.9) 7 (16.3) 0.38 Poor response,n (%) 46 (64.8) 29 (67.4) 0.38 Pro-arrhythmic response,n (%) 18 (25.4) 7 (16.3) 0.38 Patients with PVC burden≥%16 Metoprolol Succinate (n = 22) Carvedilol (n = 25) Good response,n (%) 1 (4.5) 3 (12) 0.56 Poor response,n (%) 20 (91) 20 (80) 0.56 Pro-arrhythmic response,n (%) 1 (4.5) 2 (8) 0.56 Therapeutic response to Metoprolol Succinate and Carvedilol

Assessment of Carvedilol Therapy in Prevention of Heart Failure in HER2 Positive Breast Cancer Patients Receiving Trastuzumab

Abstract- Breast cancer is the most common cancer among the female population, and its prevalence is increasing worldwide. Trastuzumab (Herceptin) therapy improves prognosis in HER2 positive patients, but Heart Failure (HF) is one of its known complications. In this study, we aimed to assess the potential benefits of prophylactic carvedilol therapy in patients receiving Herceptin. Sixty five patients with HER2 positive breast cancer were enrolled in the study. All of the patients received Herceptin. Twenty seven patients also received carvedilol 6.25 mg twice daily, and 38 patients had usual care. Echocardiography was performed at baseline, and after three months in both groups and changes in cardiac function, parameters were compared between two groups. After 3 months, LA volume index (P=0.012), TAPSE (P=0.009), Tei index (P=0.015) and Lateral Longitudinal Strain (P=0.024) were significantly better in patients receiving carvedilol. Carvedilol can be effective in the prevention of systolic and diastolic dysfunction following Herceptin therapy.

Effects of carvedilol therapy in patients with heart failure with preserved ejection fraction – Results from the Croatian heart failure (CRO-HF) registry

Background and objectiveAccording to recent guidelines, the best approach for treatment of heart failure patients with preserved ejection function is still not defined. The aim of this study was to investigate how carvedilol therapy influences the survival rate, ejection fraction and NYHA class in these patients. Patients and methodsWe conducted study on heart failure patients with preserved systolic function from the Croatian heart failure registry who were hospitalized in the period between 2005 and 2010. We enrolled patients with carvedilol listed as treatment on their discharge letters and patients who had been using carvedilol for at least 4 years, while for the control group we selected patients with no beta-blockers on their discharge letters (113 vs 204 respectively). The primary outcome was the overall survival rate and the secondary outcome was the change in ejection fraction of the left ventricle and NYHA class during the study. ResultsPatients in the carvedilol group had a higher overall survival rate compared to patients in the control group (chi-square=14.1, P<0.001). Patients in the carvedilol group in two measurements had a significantly higher ejection fraction compared to the control group (F=148.04, P<0.001). Also, patients in the carvedilol group showed improvement in NYHA class (chi-square=29.768, P<0.001). ConclusionLong term carvedilol therapy appears to be associated with a higher overall survival rate, improvement in ejection fraction and NYHA class in heart failure patients with preserved ejection fraction.

Effects of carvedilol therapy in patients with heart failure with preserved ejection fraction – Results from the Croatian heart failure (CRO-HF) registry

Background and objectiveAccording to recent guidelines, the best approach for treatment of heart failure patients with preserved ejection function is still not defined. The aim of this study was to investigate how carvedilol therapy influences the survival rate, ejection fraction and NYHA class in these patients. Patients and methodsWe conducted study on heart failure patients with preserved systolic function from the Croatian heart failure registry who were hospitalized in the period between 2005 and 2010. We enrolled patients with carvedilol listed as treatment on their discharge letters and patients who had been using carvedilol for at least 4 years, while for the control group we selected patients with no beta-blockers on their discharge letters (113 vs 204 respectively). The primary outcome was the overall survival rate and the secondary outcome was the change in ejection fraction of the left ventricle and NYHA class during the study. ResultsPatients in the carvedilol group had a higher overall survival rate compared to patients in the control group (chi-square=14.1, P<0.001). Patients in the carvedilol group in two measurements had a significantly higher ejection fraction compared to the control group (F=148.04, P<0.001). Also, patients in the carvedilol group showed improvement in NYHA class (chi-square=29.768, P<0.001). ConclusionLong term carvedilol therapy appears to be associated with a higher overall survival rate, improvement in ejection fraction and NYHA class in heart failure patients with preserved ejection fraction.

CArdiac Resynchronization In combination with BEta blocker treatment in advanced chronic Heart Failure (CARIBE-HF): the results of the CARIBE-HF study

Objective Cardiac resynchronization therapy (CRT), combined with optimal medical therapy (OMT), is an established treatment for patients with advanced chronic heart failure (ACHF). In ACHF, carvedilol at the dose used in clinical trials, reduces morbidity and mortality. However, patients often do not tolerate the drug at the targeted dosage. The aim of the CARIBE-HF prospective observational study was to investigate the role of CRT in the implementation of carvedilol therapy in patients with ACHF.Methods One hundred and six patients (aged 65 ± 12 [mean ± SD] years) with ACHF were enrolled and treated with OMT, in which carvedilol was titrated up to the maximal dose (phase 1). Subsequently, patients with left ventricular (LV) ejection fraction ≤ 35%, NYHA class III-IV and QRS interval ≥ 120 msec were assigned to CRT. Both CRT and NO-CRT patients underwent a long-term follow-up of 7 years (1193.98 ± 924 days), while eff orts to uptitrate the carvedilol dose were continued during the second phase (471 ± 310 days). Phase 1 was completed by 84 patients (79%), and 15 (18%) underwent CRT. The mean carvedilol dose in the CRT group was 19.0 ± 17.8 mg, against 32.7 ± 19.1 mg in the remaining 69 patients (P= 0.018). At the end of phase 2, CRT patients presented a signifi cantly greater variation of increasing in the carvedilol dose than NO-CRT patients (+20.0 ± 19.8 mg vs –0.3 ± 20.5 mg; P= 0.015), a greater NYHA class reduction (-0.8 ± 0.6 vs -0.2 ± 0.7; P= 0.011), and a greater increase in LV ejection fraction (10.8 ± 9 vs 3.1± 6.1; P= 0.018).Conclusions The data from the CARIBE study suggest that, in ACHF, CRT may be eff ective in enabling the target dose of carvedilol to be reached. The signifi cant improvement seen in LV function was probably due to a synergistic eff ect of CRT and carvedilol. During the extended follow-up (mean 1193.98 ± 924 days) the mean dosage of carvedilol in the CRT group was signifi cantly higher (P < 0.02).

Efficacy and Safety of Carvedilol in Treatment of Heart Failure with Chronic Kidney Disease

Background— The safety and efficacy of different types of β-blocker therapy in patients with non–dialysis-dependent chronic kidney disease (CKD) and systolic heart failure (HF) are not well described. We assessed whether treatment of systolic HF with carvedilol is efficacious and safe in adults with CKD. Methods and Results— We performed a post hoc analysis of pooled individual patient data (n=4217) from 2 multinational, double-blinded, placebo-controlled, randomized trials, CAPRICORN (Carvedilol Postinfarct Survival Control in Left Ventricular Dysfunction Study) and COPERNICUS (Carvedilol Prospective Randomized, Cumulative Survival study). Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, HF mortality, first HF hospitalization, the composite of cardiovascular mortality or first HF hospitalization, and sudden cardiac death. Non–dialysis-dependent CKD was defined by estimated glomerular filtration rate ≤60 mL/min/1.73 m 2 , using the abbreviated Modification of Diet in Renal Disease equation. CKD was present in 2566 of 4217 (60.8%) of the cohort, 50.4% of whom were randomly assigned to carvedilol therapy. Within the CKD group, treatment with carvedilol decreased the risks of all-cause mortality (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63 to 0.93; P =0.007), cardiovascular mortality (HR, 0.76; 95% CI, 0.62 to 0.94; P =0.011), HF mortality (HR, 0.68; 95% CI, 0.52 to 0.88; P =0.003), first hospitalization for HF (HR, 0.74; 95% CI, 0.61 to 0.88; P =0.0009), and the composite of cardiovascular mortality or HF hospitalization (HR, 0.75; 95% CI, 0.65 to 0.87; P &lt;0.001) but was without significant effect on sudden cardiac death (HR, 0.76; 95% CI, 0.56 to 1.05; P =0.098). There was no significant interaction between treatment arm and study type. Carvedilol was generally well tolerated by both groups of patients, with an increased relative incidence in transient increase in serum creatinine without need for dialysis and other electrolyte changes in the CKD patients. However, in a sensitivity analysis among HF subjects with estimated glomerular filtration rate &lt;45 mL/min/1.73 m 2 (CKD stage 3b), the efficacy of carvedilol was not significantly different from placebo. Conclusions— This analysis suggests that the benefits of carvedilol therapy in patients with systolic left ventricular dysfunction with or without symptoms of HF are consistent even in the presence of mild to moderate CKD. Whether carvedilol therapy is similarly efficacious in HF patients with more advanced kidney disease requires further study.

Efeito do carvedilol a curto prazo na atividade simpática cardíaca pela cintilografia com 123I-MIBG

Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG) scintigraphy imaging of the heart. to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45%. Sixteen patients, aged 56.3 +/- 12.6 years (11 males), with a mean LVEF of 28% +/- 8% and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. Patients' functional class showed improvement: before the treatment, 50% of the patients were FC II and 50% were FC III. After 3 months, 7 patients were FC I (43.8%) and 9 were FC II (56.2%), (p = 0.0001). The mean LVEF assessed by RIV increased from 29% to 33% (p = 0.017). There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. The short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by 123I-MIBG scintigraphy, as well as the measurement of circulating catecholamines.

Abstract 2083: Improvement in Coronary Flow Reserve is Associated With Late Recovery of Left Ventricular Function After Carvedilol Therapy in Patients with Idiopathic Dilated Cardiomyopathy

Background: Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in theses circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in IDC patients. Methods: We studied 20 patients with IDC (mean age 56 ± 15 years, NYHA I–II) who were scheduled to receive carvedilol therapy. All patients were stabilized using an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and diuretic treatment. Transthoracic Doppler echocardiography with intravenous infusion of adenosine triphosphate was used to assess CFR in the left anterior descending artery at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 ± 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as Group A (LVEF change ≥10%) and Group B (LVEF change &lt;10%). Results: Although there was no significant difference in CFR between the 2 groups at baseline (Group A vs. Group B, 2.4 ± 1.0 vs. 2.2 ± 0.8; P =NS), CFR was significantly higher in Group A than in Group B at 1 month of therapy (3.7 ± 0.5 vs. 2.5 ± 0.9; P &lt;0.01). The magnitude of CFR change after 1 month of therapy was significantly greater in Group A than in Group B (1.3 ± 0.6 vs. 0.4 ± 0.5; P &lt;0.01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up ( P &lt;0.05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r=0.65, P &lt;0.01). Conclusions: This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.

Relation of early improvement in coronary flow reserve to late recovery of left ventricular function after β-blocker therapy in patients with idiopathic dilated cardiomyopathy

Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in these circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in patients with IDC. Eighteen patients with IDC underwent CFR measurements by transthoracic Doppler echocardiography at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 +/- 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as group A (LVEF change > or = 10%) and group B (LVEF change < 10%). Although there was no significant difference in CFR between the 2 groups at baseline, CFR was significantly higher in group A than in group B at 1 month of therapy (3.7 +/- 0.5 vs 2.5 +/- 0.9; P < .01). Coronary flow reserve change after 1 month was significantly greater in group A than in group B (1.3 +/- 0.6 vs 0.4 +/- 0.5; P < .01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up (P < .05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r = 0.65, P < .01). This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.

Changes in Heart Rate Variability Are Correlated to Hemodynamic Improvement With Chronic CARVEDILOL Therapy in Heart Failure

Background Reduced heart rate variability (HRV) has been shown to predict mortality in heart failure (CHF). The relationship between improved cardiac function and improvement in HRV has not been previously studied. Methods and Results This was substudy of a randomized, placebo-controlled, double-blinded trial of carvedilol of four months duration. Analysis of HRV was performed on 24-hour Holter monitors obtained at baseline and completion of study. All subjects had symptomatic CHF and an left ventricular ejection fraction (LVEF) <0.35. Study medication was titrated over 1 month to 50 mg/day (≤75 kg) or 100 mg/day (<75 kg). A total of 17 subjects were randomized to carvedilol and 12 to placebo. Treatment with carvedilol was associated with significant increases in total frequency power, very low frequency power, high frequency power, SDNN, the root-mean square of difference of successive RRs, and pNN50. Change in time and frequency domain measures of HRV had a positive correlation with change in LVEF and negative correlation with change in coronary sinus norepinephrine levels. Conclusion Carvedilol therapy in patients with CHF significantly increased HRV. Change in HRV correlates to improved hemodynamics. This suggests that carvedilol therapy partially normalizes autonomic modulation of heart rate in patients with CHF.

Improvement of Left Ventricular Dyssynchrony by Carvedilol Therapy in Patients with Idiopathic Dilated Cardiomyopathy: Analysis Using Strain Echocardiography

Improvement of Left Ventricular Dyssynchrony by Carvedilol Therapy in Patients with Idiopathic Dilated Cardiomyopathy: Analysis Using Strain Echocardiography

Left Ventricular Diastolic Function Improvement by Carvedilol Therapy in Advanced Heart Failure

Carvedilol treatment in chronic heart failure (CHF) patients has been demonstrated to reduce mortality by improving cardiac systolic function and reducing left ventricular adverse remodeling. However, the effects of the drug on left ventricular (LV) filling are less studied. In this study we evaluated early and long-term diastolic cardiac modifications by an echo-Doppler method during carvedilol therapy in patients with advanced CHF and pseudonormal or restrictive filling pattern. We studied 58 patients with severe but stable CHF (39 in class NYHA III and 19 in IV) having systolic and diastolic dysfunction caused by idiopathic or ischemic cardiomyopathy. Thirty-two patients were randomized to receive previous treatment plus carvedilol (group 1) and 26 continued standard therapy (group 2). In all subjects we evaluated LV volumes, LV mass, LV ejection fraction (EF), and the following transmitral filling parameters: early wave (E), atrial wave (A), E/A ratio, deceleration time (DT), and isovolumetric releasing time (IVRT). After 4 months of therapy, the carvedilol group showed a significant increase of A wave (P < 0.001), DT (P < 0.0001), IVRT (P < 0.0001), and a significant reduction of E/A ratio (P < 0.0005) with respect to group 2. Further improvement was observed at 12 months (A P < 0.0005; DT P < 0.00002; IVRT P < 0.000004; E/A P < 0.0008), although an E wave reduction was observed in group 1 with respect to controls (P < 0.001). Moreover, after 1 year of follow-up a reduction of systolic volume (P < 0.001) and pulmonary pressure (P < 0.0001) and consequent increase of EF (P < 0.001) was observed in the carvedilol group. Carvedilol treatment improved diastolic function in CHF with severe diastolic and systolic impairment at early time, converting a restrictive or pseudonormal filling pattern into an altered pattern. These changes remained significant after 1 year of therapy together with improvement in systolic function.

Prédiction du risque d’intolérance du traitement bêtabloquant chez l’insuffisant cardiaque chronique par le dosage du BNP

Beta-blocker therapy is actually recommended as first line therapy for systolic heart failure. However, beta-blocker have a low prescription rate comparatively to ACEI. Beta-blocker potential side effects as bradycardia, hypotension and especially acute decompensation could explain this under prescription. Clinical data's could easily identify high-risk patients for hypotension or bradycardia but not high-risk patients for induced decompensation linked to beta-blocker therapy. BNP could identify these patients with a high sensitivity. Patients with BNP above 1000 pg/ml had a 40% risk of acute decompensation after introduction or increase of beta-blocker therapy. As a conclusion, clinicians must be very cautious for introducing or increasing Carvedilol therapy in patients with high BNP levels.

Neutrophils superoxide anion generation during carvedilol therapy in patients with stable angina

Neutrophil superoxide anion (O 2 ⨪) generation was measured during carvedilol therapy in patients with stable angina. The carvedilol group comprised 27 patients (18 men and 9 women), aged 38–51 years (mean 47.6 years) with stable angina. Carvedilol was administered in increased every 4-week doses: 12.5, 25 and 50 mg/24 h, respectively. The control group included 12 healthy subjects, aged 39–49 years (mean 45.7 years) with no drug administered. Blood samples were collected from cubital vein before and 4, 8 and 12 weeks after the therapy and once in the control group. Neutrophil O 2 ⨪ generation was determined in whole blood without and with opsonized zymosan (OZ) stimulation according to Bellavite et al. method using superoxide dismutase from bovine erythrocytes. O 2 ⨪ generation by nonstimulated and OZ-stimulated neutrophils was significantly higher ( p<0.05) in patients with stable angina than in the control group. In carvedilol group, statistically significant ( p<0.05) decrease in superoxide anion generation by nonstimulated and OZ-stimulated neutrophils was observed 8 and 12 weeks after the therapy and it did not differ from that in healthy subjects. Carvedilol has been shown to inhibit neutrophil O 2 ⨪ generation in patients with stable angina.

Regional myocardial free fatty acid utilization following carvedilol therapy in patients with heart failure

Regional myocardial free fatty acid utilization following carvedilol therapy in patients with heart failure

BNP plasma levels and Carvedilol Therapy in patients with Chronic Heart Failure

BNP plasma levels and Carvedilol Therapy in patients with Chronic Heart Failure

β-Blockade therapy in chronic heart failure: Diastolic function and mitral regurgitation improvement by carvedilol

Background In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this β-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear. Objective To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations. Methods Forty-five consecutive patients with chronic heart failure (ejection fraction 24% ± 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 ± 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared. Results After 6 months of treatment with carvedilol, left ventricular ejection fraction had increased from 24% ± 7% to 29% ± 9% ( P < .0001); this change was caused by a reduction in end-systolic volume index (106 ± 41 vs 93 ± 37 mL/m 2; P < .0001). Deceleration time of early diastolic filling increased (134 ± 74 vs 196 ± 63 ms; P < .0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no signigicant changes in deceleration time of early diastolic filling were found (139 ± 74 vs 132 ± 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 ± 25 vs 16 ± 13 mL; P < .0001) but not in the control group (57 ± 29 vs 47 ± 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume ( r = −.57, P < .0001). These findings were not observed in patients in the control group. Conclusions The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.

Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial

The encouraging results of recent multicenter clinical trials conducted in the US on the effect of carvedilol therapy in patients with chronic heart failure, prompted us to verify its tolerability in a group of elderly patients. For the open, randomized, placebo-controlled study, we selected 40 patients (28 men and 12 women, mean age 76.8±5.9 years) with mild, moderate or severe chronic heart failure. Exclusion criteria included dementia, chronic hepatitis, renal failure, severe vascular disease and respiratory failure. All patients were receiving treatment with digitalis, furosemide and ACE inhibitors. The study lasted 12 weeks. During the first week, all subjects received oral placebo or carvedilol, at a dose of 6.25 mg twice daily. The twice daily dose was then increased to 12.5 mg during weeks 2–4 and to 25 mg from weeks 5–12. At 0, after the 2 weeks of run-in, 4 and 12 weeks patients underwent assessment of systolic and diastolic blood pressure, heart rate, left ventricular ejection fraction, cognitive status and functional ability. Our findings indicate that elderly patients with congestive heart failure tolerate carvedilol therapy well. Carvedilol slightly improves heart function without altering functional or cognitive ability. A larger-scale trial in geriatric patients is now required to determine whether this treatment will reduce serious morbidity or mortality from heart failure.