Safety and Tolerability of Once-Daily Controlled-Release Carvedilol 10-80mg in Japanese Patients With Chronic Heart Failure

Kitakaze, Masafumi; Sarai, Nobuaki; Ando, Hidekazu; Sakamoto, Takashi; Nakajima, Hitoshi

doi:10.1253/circj.cj-11-0210

Cited by 4 publications

(4 citation statements)

References 45 publications

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“…Despite the widely held perception that Asian patients need lower dosages of medications, studies comparing dosage patterns of HF medications in Asians vs. non‐Asians are scarce . In our analysis, we found larger body size was associated with maximum prescribed dosage; however, geographic region was a strong modifier of that association.…”

Section: Baseline Characteristics By Geographical Regioncontrasting

confidence: 55%

“…Despite the widely held perception that Asian patients need lower dosages of medications, studies comparing dosage patterns of HF medications in Asians vs. non-Asians are scarce. 2,8,9 In our analysis, we found larger body size was associated with maximum prescribed dosage; however, geographic region was a strong modifier of that association. Notably, while healthcare providers might be less inclined to titrate -blocker and ACEi doses in various regions based on BSA of patients, our findings suggest that differences in patients' risk factor profiles (SBP, heart rate, eGFR) and regional practice, rather than body size per se, may influence HF dosage patterns.…”

Section: Association Between Body Surface Area and Prescribed Doses Of Guideline-directed Medications Among International Patients With Hmentioning

confidence: 44%

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Association between body surface area and prescribed doses of guideline‐directed medications among international patients with heart failure and reduced ejection fraction

Teng

Cooper

Tay

et al. 2019

European J of Heart Fail

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Section: Baseline Characteristics By Geographical Regioncontrasting

confidence: 55%

Section: Association Between Body Surface Area and Prescribed Doses Of Guideline-directed Medications Among International Patients With Hmentioning

confidence: 44%

Association between body surface area and prescribed doses of guideline‐directed medications among international patients with heart failure and reduced ejection fraction

Teng

Cooper

Tay

et al. 2019

European J of Heart Fail

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“…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). 14) Recently phase 1 and phase 2 trials in Japan have reported that 80 mg once-daily controlled-release carvedilol (Coreg CR ® ), which is equivalent to 50 mg daily of carvedilol, was well tolerated, 15) however, the long-term benefit of the high dose carvedilol therapy remains uncertain.…”

mentioning

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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“… 4 , 7 , 8 Therefore, there is a common perception that Asian patients might do with lower doses. 10 , 11 , 12 However, data relating to any sustained differences between Asian and Western populations in longitudinal titration patterns of evidence‐based anti‐HF medications are sparse.…”

Section: Introductionmentioning

confidence: 99%

Titration of medications and outcomes in multi‐ethnic heart failure cohorts (with reduced ejection fraction) from Singapore and New Zealand

et al. 2023

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Aims We investigated titration patterns of angiotensin‐converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) and beta‐blockers, quality of life (QoL) over 6 months, and associated 1 year outcome [all‐cause mortality/heart failure (HF) hospitalization] in a real‐world population with HF with reduced ejection fraction (HFrEF). Methods and results Participants with HFrEF (left ventricular ejection fraction <40%) from a prospective multi‐centre study were examined for use and dose [relative to guideline‐recommended maintenance dose (GRD)] of ACEis/ARBs and beta‐blockers at baseline and 6 months. ‘Stay low’ was defined as <50% GRD at both time points, ‘stay high’ as ≥50% GRD, and ‘up‐titrate’ and ‘down‐titrate’ as dose trajectories. Among 1110 patients (mean age 63 ± 13 years, 16% women, 26% New York Heart Association Class III/IV), 714 (64%) were multi‐ethnic Asians from Singapore and 396 were from New Zealand (mainly European ethnicity). Baseline use of either ACEis/ARBs or beta‐blockers was high (87%). Loop diuretic was prescribed in >80% of patients, mineralocorticoid receptor antagonist in about half of patients, and statins in >90% of patients. At baseline, only 11% and 9% received 100% GRD for each drug class, respectively, with about half (47%) achieving ≥50% GRD for ACEis/ARBs or beta‐blockers. At 6 months, a large majority remained in the ‘stay low’ category, one third remained in ‘stay high’, whereas 10–16% up‐titrated and 4–6% down‐titrated. Patients with lower (vs. higher) N‐terminal pro‐beta‐type natriuretic peptide levels were more likely to be up‐titrated or be in ‘stay high’ for ACEis/ARBs and beta‐blockers ( P = 0.002). Ischaemic aetiology, prior HF hospitalization, and enrolment in Singapore (vs. New Zealand) were independently associated with higher odds of ‘staying low’ (all P < 0.005) for prescribed doses of ACEis/ARBs and beta‐blockers. Adjusted for inverse probability weighting, ≥100% GRD for ACEis/ARBs [hazard ratio (HR) = 0.42; 95% confidence interval (CI) 0.24–0.73] and ≥50% GRD for beta‐blockers (HR = 0.58; 95% CI 0.37–0.90) (vs. Nil) were associated with lower hazards for 1 year composite outcome. Country of enrolment did not modify the associations of dose categories with 1 year composite outcome. Higher medication doses were associated with greater improvements in QoL. Conclusions Although HF medication use at baseline was high, most patients did not have these medications up‐titrated over 6 months. Multiple clinical factors were associated with changes in medication dosages. Further research is urgently needed to investigate the causes of lack of up‐titration of HF therapy (and its frequency), which could inform strategies for timely up‐titration of HF therapy based on clinical and biochemical parameters.

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Safety and Tolerability of Once-Daily Controlled-Release Carvedilol 10-80mg in Japanese Patients With Chronic Heart Failure

Cited by 4 publications

References 45 publications

Association between body surface area and prescribed doses of guideline‐directed medications among international patients with heart failure and reduced ejection fraction

Association between body surface area and prescribed doses of guideline‐directed medications among international patients with heart failure and reduced ejection fraction

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

Titration of medications and outcomes in multi‐ethnic heart failure cohorts (with reduced ejection fraction) from Singapore and New Zealand

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