Safety and Efficacy of Veverimer in Acidotic Patients With CKD and Heart Failure.
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ABSTRACT:
SUBMITTER: Mathur V
PROVIDER: S-EPMC8589701 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Safety and Efficacy of Veverimer in Acidotic Patients With CKD and Heart Failure.
Mathur Vandana V Li Elizabeth E Bushinsky David A DA
Kidney international reports 20210823 11
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Project description:CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m2 Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m2). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.
| S-EPMC8425606 | biostudies-literature
Project description:ObjectiveThis study aimed to investigate the safety and efficacy of vericiguat in patients with heart failure (HF).MethodsWe conducted a comprehensive literature review of the PubMed, Embase, and Cochrane Library databases up to 14 December 2022 for studies comparing vericiguat with placebo in patients with HF. Clinical data were extracted and cardiovascular deaths, adverse effects, and HF-related hospitalization were analyzed using Review Manager software (version 5.3), after quality assessment of the enrolled studies.ResultsFour studies (6705 patients) were included in this meta-analysis. There were no significant differences in the basic characteristics of the included studies. There was no significant difference in adverse effects between the vericiguat group and placebo group, and no significant differences between the groups in terms of cardiovascular death and HF hospitalization.ConclusionThis meta-analysis indicated that vericiguat was not an effective drug for HF; however, more clinical trials are required to verify its efficacy.
| S-EPMC10009045 | biostudies-literature
Project description:During the coronavirus disease 2019 (COVID-19) pandemic, it has become difficult to provide centre-based cardiac rehabilitation for heart failure patients. Digital therapeutics is a novel concept proposed in recent years that refers to the use of evidence-based therapeutic interventions driven by high-quality software programs to treat, manage, or prevent a medical condition. However, little is known about the use of this technology in heart failure patients. This study aims to explore the safety and efficacy of digital therapeutics-based cardiac rehabilitation in heart failure patients and to provide new insights into a new cardiac rehabilitation model during the COVID-19 era. To identify technologies related to digital therapeutics, such as the use of medical applications, wearable devices, and the Internet, all relevant studies published on PubMed, EMBASE, Cochrane database, and China National Knowledge Internet were searched from the time the database was established until October 2021. The PEDro was used to assess the quality of included studies. We ultimately identified five studies, which included 1119 patients. The mean age was 66.37, the mean BMI was 25.9, and the NYHA classification ranged from I to III (I = 232, II = 157, III = 209). The mean 6-min walk distance was 397.7 m. The PEDro scores included in the study ranged from 4 to 8, with a mean of 5.8. Exercise training was performed in four studies, and psychological interventions were conducted in three studies. No death or serious adverse events were observed. Adherence was reported in three studies, and all exceeded 85%. The results of most studies showed that digital therapeutics-based cardiac rehabilitation significantly increases exercise capacity and quality of life in heart failure patients. Overall, although this study suggests that digital therapeutics-based cardiac rehabilitation may be a viable intervention for heart failure patients during the COVID-19 era, the efficacy of this new model in routine clinical practice needs to be further validated in a large clinical trial.
| S-EPMC9773765 | biostudies-literature
Project description:Mineralocorticoid receptor antagonists (MRA) improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and reduce risk of heart failure (HF) hospitalization in patients with heart failure with preserved ejection fraction (HFpEF). However, the benefit and risks of MRA use are not clear in HF patients and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We conducted a systematic review evaluating the efficacy and safety of MRA in patients with HF and CKD. PubMed, Embase, and Cochrane Central databases were searched for relevant studies on patients with HF and reduced renal function (defined as eGFR <60 mL/min/1.73 m2). Seven studies with 5,522 patients were included. We found 3 studies in patients with HFrEF, 1 study with HFpEF, and 2 in acute HF and 1 with mixed patient population of HF. Post hoc analyses from randomized controlled trials demonstrated reduction of risk in the primary end point (adverse cardiovascular outcomes and/or all-cause mortality and/or HF hospitalization) with MRA use in the CKD subgroup (eGFR 30 to 60 mL/min/1.73 m2) despite a greater risk of hyperkalemia and higher rates of drug discontinuation. In 3 observational studies, propensity score matching was performed to compare patients treated with and without MRA and did not identify benefits, but conclusions from these studies were limited due to residual confounding and concern for bias. In conclusion, benefits of MRA use in HF appear to be consistent in patients with reduced renal function (eGFR 30 to 60 mL/min/1.73 m).
| S-EPMC7977068 | biostudies-literature
Project description:AimsThe aim of the LAICA study was to evaluate the long-term effectiveness and safety of intermittent levosimendan infusion in patients with advanced heart failure (AdHF).Methods and resultsThis was a multicentre, randomized, double-blind, placebo-controlled clinical trial of intermittent levosimendan 0.1 μg/kg/min as a continuous 24-h intravenous infusion administered once monthly for 1 year in patients with AdHF. The primary endpoint [incidence of rehospitalization (admission to the emergency department or hospital ward for >12 h) for acute decompensated HF or clinical deterioration of the underlying HF] occurred in 23/70 (33%) of the levosimendan group (Group I) and 12/27 (44%) of the placebo group (Group II) (P = 0.286). The incidence of hospital readmissions for acute decompensated HF (Group I vs. Group II) at 1, 3, 6, and 12 months was 4.2% vs. 18.2% (P = 0.036); 12.8% vs. 33.3% (P = 0.02); 25.7% vs. 40.7% (P = 0.147); 32.8% vs. 44.4% (P = 0.28), respectively. In a secondary pre-specified time-to-event analysis no differences were observed in admission for acute decompensated HF between patients treated with levosimendan compared with placebo (hazard ratio 0.66; 95% CI, 0.32-1.32; P = 0.24). Cumulative incidence for the aggregated endpoint of acute decompensation of HF and/or death at 1 and 3 months were significatively lower in the levosimendan group than in placebo group [5.7% vs. 25.9% (P = 0.004) and 17.1% vs. 48.1% (P = 0.001), respectively], but not at 6 and 12 months [34.2% vs. 59.2% (P = 0.025); 41.4% vs. 66.6% (P = 0.022), respectively]. Survival probability was significantly higher in patients who received levosimendan compared with those who received placebo (log rank: 4.06; P = 0.044). There were no clinically relevant differences in tolerability between levosimendan and placebo and no new safety signals were observed.ConclusionsIn our study, intermittent levosimendan in patients with AdHF produced a statistically non-significant reduction in the incidence of hospital readmissions for acute decompensated HF, a significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 month of treatment and a significant improvement in survival during 12 months of treatment.
| S-EPMC8712777 | biostudies-literature
Project description:PurposeTo evaluate the efficacy and safety of patiromer, a novel potassium binder, in reducing the risk of hyperkalemia in patients with heart failure and optimizing their RAASi therapy.DesignSystematic review and meta-analyses.MethodThe authors conducted a systematic search in Pubmed, Embase, Web of Science, and Cochrane Library for randomized controlled trials investigating the efficacy and safety of patiromer in heart failure patients from inception to 31 January 2023 and updated on 25 March 2023. The primary outcome was the association between the reduction of hyperkalemia and patiromer compared with placebo, and the secondary outcome was the association between optimization of RAASi therapy and patiromer.ResultsA total of four randomized controlled trials (n = 1163) were included in the study. Patiromer was able to reduce the risk of hyperkalemia in heart failure patients by 44% (RR 0.56, 95% CI 0.36 to 0.87; I2 = 61.9%), improve tolerance to target doses of MRA in patients with heart failure (RR 1.15, 95% CI 1.02 to 1.30; I2 = 49.4%), and decrease the proportion of all-cause discontinuation of RAASi (RR 0.49, 95% CI 0.25 to 0.98; I2 = 48.4%). However, patiromer therapy was associated with an increased risk of hypokalemia (RR 1.51, 95% CI 1.07 to 2.12; I2 = 0%), while no other statistically significant adverse events were observed.ConclusionPatiromer appears to have a considerable effect on reducing the incidence of hyperkalemia in heart failure patients and on optimizing the therapy of RAASi in those patients.
| S-EPMC11680614 | biostudies-literature
Project description:BackgroundPatients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF.MethodsWe conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month.ResultsA total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable.ConclusionsTolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.
| S-EPMC9692217 | biostudies-literature
Project description:To determine the safety and efficacy of nebivolol in elderly heart failure (HF) patients with renal dysfunction.SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67-1.07), 31% and 0.79 (0.60-1.04) in the middle tertile, and 29% and 0.86 (0.65-1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect (P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia.Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
| S-EPMC2729679 | biostudies-other
Project description:CKD is a risk factor for heart failure, but there is no data on the risk of ESRD and death after recurrent hospitalizations for heart failure. We sought to determine how interim heart failure hospitalizations modify the subsequent risk of ESRD or death before ESRD in patients with CKD. We retrospectively identified 2887 patients with a GFR between 15 and 60 ml/min per 1.73 m2 referred between January of 2001 and December of 2008 to a nephrology clinic in Toronto, Canada. We ascertained interim first, second, and third heart failure hospitalizations as well as ESRD and death before ESRD outcomes from administrative data. Over a median follow-up time of 3.01 (interquartile range=1.56-4.99) years, interim heart failure hospitalizations occurred in 359 (12%) patients, whereas 234 (8%) patients developed ESRD, and 499 (17%) patients died before ESRD. Compared with no heart failure hospitalizations, one, two, or three or more heart failure hospitalizations increased the adjusted hazard ratio of ESRD from 4.89 (95% confidence interval [95% CI], 3.21 to 7.44) to 10.27 (95% CI, 5.54 to 19.04) to 14.16 (95% CI, 8.07 to 24.83), respectively, and the adjusted hazard ratio death before ESRD from 3.30 (95% CI, 2.55 to 4.27) to 4.20 (95% CI, 2.82 to 6.25) to 6.87 (95% CI, 4.96 to 9.51), respectively. We conclude that recurrent interim heart failure is associated with a stepwise increase in the risk of ESRD and death before ESRD in patients with CKD.
| S-EPMC4341483 | biostudies-literature
Project description:The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo.Depression is common among HF patients. It is associated with increased hospitalization and mortality.The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks.A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78).Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).
| S-EPMC3663330 | biostudies-literature