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

Abstract

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...

Importance of baseline heart rate as a predictor of cardiac functional recovery in newly diagnosed heart failure with reduced ejection fraction

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