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Outpatient Management of Stable Heart Failure with Reduced Ejection Fraction
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Leah Reid, Jonathan Murrow, Kent Nilsson, Catherine Marti
The overall clinical goal is to achieve the highest tolerated dose, best done by starting with a low dose and increasing the dose over time while being mindful of precipitating fluid retention among those without concurrent diuretic therapy. MERIT-HF11 showed a mortality reduction of over 30% when targeting 200 mg/day. This dose was achieved in 64% of patients; the mean dose was 159 mg/day.5 In the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) trial, four out of five patients reached the target dose of 50 mg daily.12 Furthermore, side effects reported with carvedilol were actually less than those reported with placebo. Importantly, reactive airways disease or asymptomatic bradycardia should not necessarily constrain the use of beta-blockers.13 In most health systems, beta-blocker prescription costs are low, yielding an Incremental Cost Effectiveness Ratio of only $34/quality-adjusted life years in one analysis.14
Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Carvedilol is a newer substance of particular interest in heart failure because it has both alpha-adrenergic and beta-adrenergic action (the latter is non-specific, in contrast to metoprolol which is cardiospecific). Carvedilol differs from other beta-blockers by being a vasodilator. It has been used successfully in children with heart failure secondary to left ventricular dysfunction [21,22]. Initial doses as low as 10 mcg/kg/day have been recommended, increasing slowly, by weekly increments, to 200 mcg/kg/day; the maximum dose is 700 mcg/kg/day.
Survivorship: Pediatric cancer survivors
Published in Susan F. Dent, Practical Cardio-Oncology, 2019
Shahnawaz Amdani, Neha Bansal, Emma Rachel Lipshultz, Michael Jacob Adams, Steven E. Lipshultz
Carvedilol is a combination of a nonselective beta-blocker and an α-1 blocker. In rats, its antioxidant activity protected against doxorubicin-induced mitochondrial damage (174). In children with ALL, pretreatment with carvedilol before Adriamycin administration reduced troponin I and lactate dehydrogenase concentrations after treatment more than concentrations in patients not pretreated with carvedilol. Also, pretreated patients had significantly higher LVFS and global peak systolic strain than did nontreated patients (175). In a more recent randomized trial in women with breast cancer about to receive anthracyclines, prophylactic carvedilol preserved LVEF and significantly lowered cTnI concentrations 30 days after treatment (176).
New and developing pharmacotherapies for hypertension
Published in Expert Review of Cardiovascular Therapy, 2022
Christian Höcht, Miguel A Allo, Ariel Héctor Polizio, Marcela A Morettón, Andrea Carranza, Diego A Chiappetta, Marcelo Roberto Choi
Another point of great relevance is the lack of adequate formulations for paediatric patients [179]. It is estimated that 4% of the paediatric population is affected by hypertension and is exposed to a greater risk of developing adult hypertension and metabolic syndrome [180]. Adequate screening, diagnosis, and treatment of paediatric hypertension can prevent one of the 10 cases of hypertension in adults [180]. Carvedilol is only available in solid dosage forms, which can be a real problem for those paediatric patients who cannot swallow tablets [181]. For this reason, Wegmann et al. developed a novel carvedilol paediatric liquid formulation based on polymeric nanomicelles [182]. This formulation showed an increase in oral bioavailability of 4.95-fold versus a drug formulation currently employed in a paediatric hospital (Garrahan Paediatric Hospital, Argentina) [181,182].
Oral ivermectin for the treatment of red scrotum syndrome
Published in Journal of Dermatological Treatment, 2022
Jose Dario Martinez, Manuel Soria Orozco, Jesus Alberto Cardenas-de la Garza
To our knowledge this is the first report in literature to examine and describe successful treatment with oral ivermectin. The successful clinical outcome is hypothesized to be due to ivermectin’s profile in reducing the priming and activation of specific T cells, as well as reducing the production of inflammatory cytokines and vascular inflammation (2). Other therapeutic options addressed to the vascular component of RSS have been reported. Indeed, anecdotal case reports have found oral carvedilol, a β-2 adrenergic blocker, to be a therapeutic option in managing red vulva syndrome and RSS (3,4). Carvedilol, besides the β-blocker and vasoconstriction effect, seems to have also antioxidant and anti-inflammatory effects with clinical response 3 weeks after initiation of treatment (4,5). However, carvedilol dose should be adjusted to minimize risks and adverse effects (e.g. orthostatic effects, hypotension, dizziness, and bradycardia) (3). Topical timolol was reported effective in a patient that previously failed oral carvedilol therapy (6).
Blood pressure targets and pharmacotherapy for hypertensive patients on hemodialysis
Published in Expert Opinion on Pharmacotherapy, 2020
Takashi Maruyama, Hiroyuki Takashima, Masanori Abe
The results of the BLOCADE study were recently reported [125]. Seventy-two patients who were undergoing hemodialysis or peritoneal dialysis were treated with carvedilol for a run-in period of 6 weeks, and those who tolerated carvedilol at 6.25 mg twice daily were randomly assigned to receive carvedilol (up to 25 mg twice daily) or placebo. The primary outcome was the proportion of patients who tolerated carvedilol at 6.25 mg twice daily during the run-in period. Forty-nine of 72 patients achieved the primary outcome. Twenty-six of these 49 patients were then allocated to a carvedilol group and 23 to a placebo group. Overall, the withdrawal rate and the incidence of intra-dialytic hypotension were comparable between the two groups. This study could not recruit the intended number of patients because of its narrow inclusion criteria and the high number of dropouts at all stages. Despite the possible therapeutic outcome of β-blockers in patients on dialysis, the evidence from randomized controlled investigations of efficacy is limited to these two trials. Further studies are needed to clarify the potential use of β-blockers to improve cardiovascular mortality before a recommendation can be made. However, β-blockers are prescribed as first-line antihypertensive therapy in patients on hemodialysis in the absence of supporting studies. Table 4 summarizes the clinical studies performed to elucidate the effect of β-blockers on cardiovascular outcomes in patients on dialysis [56,120,125].