Clinical trials update from the American Heart Association meeting 2009: HEAAL, FAIR‐HF, J‐CHF, HeartMate II, PACE and a meta‐analysis of dose‐ranging studies of beta‐blockers in heart failure

Cleland, John G.F.; Coletta, A; Freemantle, Nick; Ahmed, Daniyal; Rubiś, Paweł; Clark, Andrew L.

doi:10.1093/eurjhf/hfp199

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…Furthermore, the J-CHF study randomly assigned systolic HF patients into 3 groups (carvedilol 2.5, 10, and 20 mg/day) and did not observe any dose-dependent efficacy in terms of the primary composite endpoint (death or cardiovascular hospitalizations). 22) However, these two studies were performed with 20 mg of carvedilol and included patients with various etiologies, such as ischemic cardiomyopathy. In the MOCHA study, 19) the dose-dependent increase in LVEF was only remarkable in the patients with idiopathic non-ischemic cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…was slightly less effective . A recent meta‐analysis of these and other dose‐ranging studies of beta‐blockers showed a non‐significant trend to greater reduction in mortality in patients assigned to a substantial dose of beta‐blocker compared with low or very low doses [HR 0.69 (95% CI 0.34–1.37)], but more side effects leading to discontinuation of study medication with higher doses . Beta‐blockers may retard worsening symptoms but there is little evidence that they improve quality of life .…”

Section: Discussionmentioning

confidence: 99%

“…Adequate dose‐ranging studies in patients with heart failure have not been conducted. A meta‐analysis of small dose‐ranging studies suggested a trend to greater effect with higher doses, but did not adjust for effects on heart rate . On the other hand, higher doses were definitely associated with more adverse events.…”

Section: Introductionmentioning

confidence: 99%

Heart rate achieved or beta‐blocker dose in patients with chronic heart failure: which is the better target?

Cullington

Goode

Clark

et al. 2012

European J of Heart Fail

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AimsTo investigate whether the mortality of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) is more strongly related to beta-blocker dose or to heart rate. It is known that beta-blockers reduce mortality in patients with CHF and LVSD, but the primary mechanism of action is uncertain. Methods and resultsPatients with an ejection fraction ≤40%, who were in sinus rhythm both at an initial (visit 1) and at a 4-month clinic review (visit 2), were followed for a maximum of 36 months. The relationships between heart rate, beta-blocker dose, and survival in a multivariable model were examined. Of 654 eligible patients, 381 (58%) were started on beta-blockers prior to the initial visit, increasing to 537 (82%) by visit 2. During follow-up, 142 (22%) patients died. Neither resting heart rate nor beta-blocker dose at visit 1 predicted mortality (P ¼ 0.09 and P ¼ 0.99), but resting heart rate at visit 2 did (P ¼ 0.02). Beta-blocker use at visit 2 was associated with better outcome (P ¼ 0.03) but with little variation in outcome according to dose. Patients with a heart rate of 58 -64 b.p.m. at visit 2 had the best prognosis. ConclusionsThe use of beta-blockers and resting heart rate at visit 2 both independently indicated prognosis, but beta-blocker dose did not. Beta-blockers may reduce mortality by several mechanisms; one that may be specific to blockade of adrenergic receptors and another related to heart rate reduction. Achieving a target heart rate range may be an appropriate therapeutic goal for patients with CHF.--

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“…More research is required to determine whether patients prefer heart rate control with ivabradine or beta‐blockers and whether a strategy of low‐dose beta‐blocker plus ivabradine is as safe as full‐dose beta‐blockers 23,24. There is little evidence that higher doses of beta‐blockers are more effective than lower doses, but side effects do increase with dose 25. Attaining a resting heart rate of 50–60 b.p.m.…”

Section: Shift: Systolic Heart Failure Treatment With the I(f) Inhibimentioning

confidence: 99%

Clinical trials update from the European Society of Cardiology Meeting 2011: ARISTOTLE, SMART‐AV: QLV substudy, SHIFT: echocardiography and quality of life substudies, European CRT Survey, and Basic Science Update

Cleland

Coletta

Cullington

et al. 2011

European J of Heart Fail

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This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the European Society of Cardiology meeting held in Paris, France in August 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Results from ARISTOTLE suggest that apixaban is more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. Electrical dyssynchrony, measured by the time from onset of electrical activity on the surface ECG to activation of myocardium by intrinsic conduction at the pacing site (QLV), was a strong and independent predictor of improvement in ventricular function after cardiac resynchronization therapy (CRT) in an observational analysis of a subgroup of patients from the SMART-AV study. Subgroup analyses from SHIFT suggest that heart rate reduction with ivabradine causes favourable left ventricular remodelling and improves quality of life in patients with symptomatic systolic heart failure and an increased heart rate. The European CRT Survey reported outcome data.--

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Clinical trials update from the American Heart Association meeting 2009: HEAAL, FAIR‐HF, J‐CHF, HeartMate II, PACE and a meta‐analysis of dose‐ranging studies of beta‐blockers in heart failure

Cited by 13 publications

References 21 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

Heart rate achieved or beta‐blocker dose in patients with chronic heart failure: which is the better target?

Clinical trials update from the European Society of Cardiology Meeting 2011: ARISTOTLE, SMART‐AV: QLV substudy, SHIFT: echocardiography and quality of life substudies, European CRT Survey, and Basic Science Update

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