Predictors of Stable Outcome in Treating Chronic Heart Failure Patients With Carvedilol

Ho, Wan-Jing; Tsay, Pei-Kwei; Chu, Po-Hsien; Chang, Chi-Jen; Kuo, Chi‐Tai; Chen, Wen‐Jone

doi:10.1536/jhj.45.823

Cited by 5 publications

(3 citation statements)

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“…In addition, genetic differences in the responses to BBs have also been suggested as the reason for the small dose among Japanese, 11) however, there is a report that 25 mg of carvedilol was well tolerated among Chinese who might be considered to be genetically similar to Japanese. 12) There is anecdotal experience in which carvedilol was used at a dose above 20 mg daily in Japan, 13) but the report was limited to 5 patients receiving ventricular assist devices. Fur-thermore, we reported a case that showed significant left ventricular reverse remodeling (LVRR) after the titration of 40 mg/day of carvedilol under the pacing of cardiac resynchronization therapy (CRT).…”

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High Dose <i>β</i>-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic Cardiomyopathy

et al. 2016

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SummaryCarvedilol has established its evidence to improve prognosis and facilitate left ventricular reverse remodeling (LVRR) in heart failure patients with reduced left ventricular ejection fraction (LVEF), and many studies have supported its dose-dependency. However, there are few studies demonstrating the effect of high dose carvedilol in Japan. We enrolled 23 patients with idiopathic non-ischemic cardiomyopathy, in whom LVEF remained 45% or less despite 20 mg/ day of carvedilol therapy for > 3 months. After high dose (40 mg/day) carvedilol therapy for > 3 months, LVEF improved (+9.1%, P = 0.002), and LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs) reduced (-4.6 and -6.9 mm, respectively, P < 0.05) compared with the baseline data. Finally, 17 patients achieved LVRR after the high dose, when LVRR was defined as 1) those with final EF > 45%, and 2) those with final EF < 45% but who attained increases in LVEF > 10%, or LVEF > 5% with a decrease in LV end-diastolic dimension index (LVDDI) > 5%. Baseline predictors for LVRR after high dose carvedilol were the change rates of log B-type natriuretic peptide (BNP), LVDd, and LVDs from the time of pre-carvedilol introduction to enrollment (P < 0.05, respectively). In conclusion, high dose carvedilol triggered additional LVRR in patients with idiopathic non-ischemic cardiomyopathy and the change rates of log BNP, LVDd, and LVDs at 20 mg carvedilol may be predictors for the additional LVRR at high dose. (Int Heart J 2016; 57: 717-724) Key words: Carvedilol, Heart failure, Ejection fraction β -Blockers (BBs) have established the evidence to improve the prognosis of chronic heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), [1][2][3] and are recommended as one of the first line drugs in all HF guidelines. 4,5) Among the 3 BBs that have been shown to be effective in systolic HF, ie, carvedilol, bisoprolol, and metoprolol succinate, carvedilol has been used the most all over the world. [6][7][8] The approved maximal dose is 20 mg/day in Japan, whereas its standard dose in the United States and Europe is 50 mg/day. HF guidelines from the US 4) and Europe 5) state that BBs should be titrated as much as tolerated. However, a post-marketing surveillance study in Japanese HF patients reported that carvedilol was then prescribed at approximately 7.2 mg/day on average. 9) Similarly, the mean dosage of carvedilol was 25 mg/day, ie, half of the target dose in Europe in the SHIFT study.10) As such, BBs are underused in terms of their dosage in real-world clinical practice.When a new drug is introduced into Japan, approximately the half dose of that in Western countries has often been adopted as the maximal dose for Japanese simply because of their smaller average build. In most Japanese clinical trials, the protocols set the target dose of any medications relatively low. This was also the case for carvedilol. However, probably because of the Westernization of Japanese dietary habits, the improvement in the average build is q...

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High Dose <i>β</i>-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic Cardiomyopathy

et al. 2016

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“…[3][4][5][6][7] Carvedilol is an antihypertensive agent which possesses both alpha 1 and beta-receptor blocking properties. [8][9][10][11] In this study, our objective was to evaluate the effects of carvedilol versus atenolol and doxazosin on metabolic parameters in hypertensive patients with MetS.…”

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The Effect of Carvedilol on Metabolic Parameters in Patients With Metabolic Syndrome

2006

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The objective of the present study was to explore the effect of carvedilol treatment on metabolic parameters in patients with metabolic syndrome. A total of 77 patients > or = 20 years of age (59 females, 18 males, mean age, 52.3 +/- 10.3) with stage 1 hypertension who fulfilled at least 3 of the metabolic syndrome criteria proposed by NCEP-ATP III were included in this prospective, randomized, controlled study. Patients were randomly assigned to receive daily treatment with carvedilol (n = 27, 12.5 mg/day orally for the first 2 days and 25 mg/day thereafter), atenolol (n = 26, 50 mg/day orally), or doxazosin (n = 24, 2 mg/day orally) for 90 days. Doses were doubled at the end of the 3rd week in patients whose blood pressure was inadequately controlled and amlodipine 10 mg was added to the treatment if the target blood pressure was still not reached at the end of week 6. The biochemical parameters and insulin sensitivity based on the HOMA-IR model were evaluated at baseline and at the end of treatment. Similar reductions in systolic and diastolic blood pressure were observed in all groups (P > 0.05). A significant decrease in HDL cholesterol levels occurred in the doxazosin and atenolol groups compared to the carvedilol group (percent change: -5.6 +/- 13.5 and -8 +/- 9.8 versus -0.1 +/- 12.2, respectively; P < 0.05) and a significant increase in apolipoprotein A1 level was observed in the carvedilol group compared to the doxazosin and atenolol groups (percent change: + 4.3 +/- 9.6 versus - 0.5 +/- 10.6 and -2.3 +/- 6.6, respectively; P < 0.05). There were no significant differences among the groups with respect to other parameters. It is concluded antihypertensive treatment with carvedilol in patients with metabolic syndrome effectively reduces blood pressure without adversely affecting metabolic parameters.

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“…Investigation in humans suggests that carvedilol administration is effective in advanced disease (ie, EF ,25% 4,5 ) as well as in very elderly patients 28 ; however, one report indicated that response was suboptimal in patients with larger heart sizes, worse systolic function, and more advanced clinical heart failure class. 29 Advanced canine DCM is accom- panied by progressive myocyte loss due to necrosis, apoptosis, atrophy, and fibrous or fatty infiltration. 30,31 The remaining myocytes demonstrate significant abnormalities of transcription of basic cellular components as well as deficiencies in mitochondrial protein expression.…”

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Carvedilol in Dogs with Dilated Cardiomyopathy

et al. 2007

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Background: Dilated cardiomyopathy (DCM) is characterized by reduced systolic function, heightened sympathetic tone, and high morbidity and mortality. Little is known regarding the safety and efficacy of b-blocker treatment in dogs with DCM.Hypothesis: Carvedilol improves echocardiographic and neurohormonal variables in dogs with DCM over a 4-month treatment period.Methods: Prospective, placebo-controlled, double-blinded randomized study. Dogs with DCM underwent echocardiography, ECG, thoracic radiographs, and neurohormonal profiling, followed by titration onto carvedilol (0.3 mg/kg q12h) or placebo over a 4-week period and subsequently received 3 months of therapy. Primary study endpoints included left ventricular volume and function.Results: Sixteen dogs received carvedilol and 7 received placebo. At study end, 13 carvedilol dogs and 5 placebo dogs were alive. There was no difference in the mean percentage change in left ventricular volume at end-diastole (LVVd), left ventricular end-systolic volume (LVVs), and ejection fraction (EF) between treatment groups, suggesting that both groups experienced similar amounts of disease progression. Carvedilol treatment did not result in significant changes in neurohormonal activation, radiographic heart size, heart rate, or owner perceived quality-of-life. Baseline B-type natriuretic peptide (BNP) predicted dogs in the carvedilol-treated group that maintained or improved their EF over the study duration.Conclusions and Clinical Importance: Carvedilol administration did not improve echocardiographic or neurohormonal indicators of heart function. The lack of effect may be related to severity of disease, carvedilol dose, or brevity of follow-up time. Statistical power of the present study was adversely affected by a high fatality rate in study dogs and small sample size.

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Predictors of Stable Outcome in Treating Chronic Heart Failure Patients With Carvedilol

Cited by 5 publications

References 20 publications

High Dose <i>β</i>-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic Cardiomyopathy

High Dose <i>β</i>-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic Cardiomyopathy

The Effect of Carvedilol on Metabolic Parameters in Patients With Metabolic Syndrome

Carvedilol in Dogs with Dilated Cardiomyopathy

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