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Value in Health : the Journal of the... Oct 2023Decision-analytic models (DAMs) with varying structures and assumptions have been applied in economic evaluations (EEs) to assist decision making for heart failure with... (Review)
Review
OBJECTIVES
Decision-analytic models (DAMs) with varying structures and assumptions have been applied in economic evaluations (EEs) to assist decision making for heart failure with reduced ejection fraction (HFrEF) therapeutics. This systematic review aimed to summarize and critically appraise the EEs of guideline-directed medical therapies (GDMTs) for HFrEF.
METHODS
A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists.
RESULTS
A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold.
CONCLUSIONS
Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context.
Topics: Humans; Heart Failure; Cost-Benefit Analysis; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Angiotensin-Converting Enzyme Inhibitors
PubMed: 37236395
DOI: 10.1016/j.jval.2023.05.011 -
BMJ Open Respiratory Research Aug 2023Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.
DESIGN
Systematic review.
ELIGIBILITY
Quantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.
DATA SOURCE
PubMed and Embase (1 January 2020-28 September 2022).
RISK OF BIAS
Cochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.
DATA ANALYSIS
Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available.
RESULTS
In all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.
CONCLUSIONS
Results from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.
PROSPERO REGISTRATION NUMBER
CRD42021292797.
Topics: Adult; Humans; COVID-19; Pandemics; SARS-CoV-2; Angiotensin Receptor Antagonists; Hydroxychloroquine; Ivermectin; Angiotensin-Converting Enzyme Inhibitors; Primary Prevention
PubMed: 37640510
DOI: 10.1136/bmjresp-2023-001674 -
Frontiers in Immunology 2023IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence.
METHODS
We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included.
RESULTS
Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19).
CONCLUSIONS
This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.
Topics: Humans; Male; Glomerulonephritis, IGA; Kidney Transplantation; Risk Factors; Kidney Failure, Chronic; Mycophenolic Acid
PubMed: 38090563
DOI: 10.3389/fimmu.2023.1277017 -
Drug Safety May 2024Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug...
BACKGROUND
Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.
PURPOSE
The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.
DATA SOURCES
The PubMed and EMBASE databases were searched up to November, 1st 2023.
STUDY SELECTION
We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.
DATA EXTRACTION
Two authors independently extracted the data.
DATA SYNTHESIS
Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced C and delayed t of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.
LIMITATIONS
The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).
CONCLUSIONS
To conclude, reduced C and delayed t of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Interactions; Glucagon-Like Peptide 1; Warfarin
PubMed: 38273155
DOI: 10.1007/s40264-023-01392-3 -
Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
Cureus Feb 2024Heart failure (HF) is a major cause of morbidity and mortality and imposes a significant financial burden on healthcare systems globally. Angiotensin receptor-neprilysin... (Review)
Review
Heart failure (HF) is a major cause of morbidity and mortality and imposes a significant financial burden on healthcare systems globally. Angiotensin receptor-neprilysin inhibitor (ARNI), a novel neuroendocrine inhibitor, is frequently used in treating HF. However, there is still limited understanding regarding how it compares to other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). The purpose of this research is to present the most recent data regarding the efficacy and renal impact of ARNIs in the treatment of HF in comparison to ACE inhibitors and ARBs. Several large-scale randomized controlled trials (RCTs) have recently been conducted to evaluate the benefits of this drug in patients with different types of HF, regardless of their renal status. We searched multiple databases, including PubMed, PubMed Central (PMC), and Google Scholar, to find relevant RCTs. The efficacy outcome was a composite of the rate of death from cardiovascular causes, the frequency of HF hospitalizations (HFH), and alterations in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The renal outcome was impairment of renal function. This systematic review analyzed large-scale RCTs involving 17,327 participants, with an average follow-up time of approximately 2.9 years. sacubitril/valsartan showed notable improvements compared to ACEis and ARBs in the following areas: reduction in NT-proBNP levels, prevention of further deterioration in renal function, and decreased hospitalizations for HF. Interestingly, there is no increased risk of mortality from cardiovascular causes with sacubitril or valsartan.
PubMed: 38516430
DOI: 10.7759/cureus.54501 -
Journal of Cardiovascular Pharmacology Jan 2024Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior... (Meta-Analysis)
Meta-Analysis
Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.
Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Shock, Septic; Retrospective Studies; Kidney
PubMed: 37815234
DOI: 10.1097/FJC.0000000000001491 -
Clinical Cardiology Oct 2023Sacubitril-valsartan (SV) monotherapy has been shown to help patients with Heart failure with reduced ejection fraction (HFrEF), but whether adding a sodium-glucose... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sacubitril-valsartan (SV) monotherapy has been shown to help patients with Heart failure with reduced ejection fraction (HFrEF), but whether adding a sodium-glucose cotransporter-2 inhibitor (SGLT2i) improves treatment results even more is unknown.
HYPOTHESIS
The goal of this study was to look at the efficacy of SV with additional SGLT2i in HFrEF patients.
METHODS
For this study, several databases, such as PubMed, EMBASE, Web of Science, and the Cochrane Library, were searched. A coherent search approach was used for data extraction. Review Manager 5.2 and MedCalc were used for conducting the meta-analysis and bias analysis. A meta-regression study correlates patient mean age with primary and secondary outcomes.
RESULTS
Seven trials totaling 16 100 patients were included in this meta-analysis. All-cause mortality, cardiovascular mortality, and improvement in mean left ventricular ejection fraction (LVEF) were the study's major objectives, while hospitalization for heart failure (HF) was calculated to be its secondary outcome. Our analysis showed that HFrEF patients receiving the combination of SV and SGLT2i had better treatment outcomes than the standard SV monotherapy, with risk ratios of 0.76 (0.65-0.88) for all-cause mortality, 0.65 (0.49-0.86) for cardiovascular mortality, 1.41 (-0.59 to 3.42) for change in mean LVEF, and 0.80 (0.64-1.01) for hospitalization for HF. According to the regression analysis, older HFrEF patients have higher rates of hospitalization, cardiovascular disease, and overall death.
CONCLUSIONS
The combination of SV and SGLT2i may have a greater cardiovascular protective effect and minimize the risk of death or hospitalization due to heart failure in HFrEF.
Topics: Humans; Heart Failure; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left; Tetrazoles; Angiotensin Receptor Antagonists; Drug Combinations
PubMed: 37465885
DOI: 10.1002/clc.24085 -
ESC Heart Failure Jun 2024Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by...
AIMS
Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by vaccination.
METHODS AND RESULTS
We did a systematic review, searching PubMed, Embase, Web of Science, Ovid MEDLINE, Journals@Ovid, and Scopus databases up to 26 April 2023 to identify case reports or case series of vaccine-induced TTS. We then extracted and summarized the data from these reports. Eighteen reports were identified, with a total of 19 patients with TTS associated with vaccinations. Of the 19 included patients, the majority were female (n = 13, 68.4%) with a mean age of 56.6 ± 21.9 years. Seventeen patients developed TTS after coronavirus disease 2019 vaccination, 14 of whom received an mRNA vaccination. Two cases of TTS occurred after influenza vaccination. Among the 19 patients, 17 (89.5%) completed transthoracic echocardiography and 16 (84.2%) underwent angiography procedures. Seven patients (36.8%) completed cardiac magnetic resonance imaging. The median time to symptom onset was 2 (inter-quartile range, 1-4) days. The most common symptoms were chest pain (68.4%), dyspnoea (57.9%), and digestive symptoms (31.6%). A total of 57.9% of patients developed nonspecific symptoms such as fatigue, myalgia, diaphoresis, and fever. Among the 16 reported cases of TTS, 15 patients (93.8%) exhibited elevated cardiac troponin levels, while among the nine reported cases, eight patients (88.9%) had elevated natriuretic peptide levels. All patients had electrocardiographic changes: ST-segment change (47.1%), T-wave inversion (58.8%), and prolonged corrected QT interval (35.3%). The most common TTS type was apical ballooning (88.2%). Treatment during hospitalization typically included beta-blockers (44.4%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (33.3%), and diuretics (22.2%). After treatment, 81.3% of patients were discharged with improved symptoms. Among this group, nine patients (56.3%) were reported to have recovered ventricular wall motion during follow-up. Two patients (12.5%) died following vaccination without resuscitation attempts.
CONCLUSIONS
TTS is a rare but potentially life-threatening complication of vaccination. Typical TTS symptoms such as chest pain and dyspnoea should be considered alarming symptoms, though nonspecific symptoms are common. The risks of such rare adverse events should be balanced against the risks of infection.
Topics: Humans; Takotsubo Cardiomyopathy; COVID-19 Vaccines; COVID-19; Vaccination; SARS-CoV-2; Echocardiography
PubMed: 38344896
DOI: 10.1002/ehf2.14719 -
High Blood Pressure & Cardiovascular... Mar 2024Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg...
Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Drug Resistance; Drug Therapy, Combination; Hypertension; Precision Medicine; Treatment Outcome
PubMed: 38616212
DOI: 10.1007/s40292-024-00634-4