P1434ALDOSTERONE ANTAGONISTS FOR PATIENTS UNDERGOING DIALYSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background and Aims Patients with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular mortality and morbidity. Several clinical trials suggested that aldosterone antagonists would be a promising treatment option for patients undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for patients with CKD on dialysis have yet to be determined. This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 14 trials (12 parallel RCTs and two cross-over trials) involving a total of 1,375 participants. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 participants: RR 0.45, 95% CI 0.30 to 0.67; I=0%; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I=0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I=0%; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I=0%; moderate certainty of evidence), the elevated risk of hyperkalaemia (9 trials, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I=47%; low certainty of evidence) and increase in serum potassium (7 trials, 519 participants: MD 0.21, 95% CI -0.06 to 0.47; I2=84%) due to aldosterone antagonists was uncertain. Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (7 trials, 562 participants: SMD -0.33, 95% CI -0.72 to 0.05; I2=76%). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis. Two ongoing studies will provide better certainty of evidence in the future.

Download Full-text

MO817ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab098.009 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Takeshi Hasegawa ◽

Hiroki Nihiwaki ◽

Erika Ota ◽

William Levack ◽

Hisashi Noma

Keyword(s):

Chronic Kidney Disease ◽

High Risk ◽

Kidney Disease ◽

Standard Care ◽

Meta Analysis ◽

Cardiovascular Death ◽

Aldosterone Antagonists ◽

Mortality And Morbidity ◽

Risk Of Death ◽

Increased Risk

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.

Download Full-text

Dexamethasone in Patients with Spontaneous Intracerebral Hemorrhage: An Updated Meta-Analysis

Cerebrovascular Diseases ◽

10.1159/000510040 ◽

2020 ◽

Vol 49 (5) ◽

pp. 495-502

Author(s):

Stephanie Wintzer ◽

Josef Georg Heckmann ◽

Hagen B. Huttner ◽

Stefan Schwab

Keyword(s):

Clinical Trials ◽

High Risk ◽

Intracerebral Hemorrhage ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Risk Of Bias ◽

Spontaneous Intracerebral Hemorrhage ◽

Control Groups ◽

Language Data ◽

Negative Effect

Background: Spontaneous intracerebral hemorrhage (ICH) is a frequent cerebrovascular disorder and still associated with high mortality and poor clinical outcomes. The purpose of this review was to update a 15-year-old former meta-analysis on randomized clinical trials (RCTs) addressing the question of whether ICH patients treated with dexamethasone have better outcomes than controls. Methods: The electronic databases PubMed, SCOPUS, and Cochrane as well as web platforms on current clinical trials were searched for the years 1970–2020 without constriction on language. Data were extracted and outcomes were pooled for conventional and cumulative meta-analysis using a commercial software program (www.Meta-Analysis.com). Results: Finally, 7 RCTs were identified and analyzed including 248 participants in the dexamethasone groups and 242 in the control groups. Five studies showed a high risk of bias. The overall relative risk (RR) for death was 1.32 (95% confidence interval [CI] 0.99–1.76; p = 0.06) and did not differ significantly between the 2 groups. After exclusion of studies with high risk of bias, the RR for death was 1.37 (95% CI 0.54–3.42; p = 0.51). The RR for poor outcome did not differ significantly between the 2 groups analyzed for all included studies (RR = 0.69; 95% CI 0.47–1; p = 0.05) and after exclusion of studies with high risk of bias (RR = 0.7; 95% CI 0.45–1.08; p = 0.11). The RR for complications did not differ significantly including all studies (RR = 1.29; 95% CI 0.77–2.17; p = 0.34) and after exclusion of studies with high risk of bias (RR = 1.27; 95% CI 0.18–8.89; p = 0.81). The cumulative statistics delivered no other results; however, it pointed out fewer complications over time in the dexamethasone group. Conclusion: Clear evidence of a beneficial or negative effect of dexamethasone is still lacking. Modern RCTs or observational studies with propensity design are necessary to evaluate the efficacy and safety of treatment with dexamethasone in patients with ICH.

Download Full-text

Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ ◽

10.1136/bmj.m2980 ◽

2020 ◽

pp. m2980 ◽

Cited By ~ 49

Author(s):

Reed AC Siemieniuk ◽

Jessica J Bartoszko ◽

Long Ge ◽

Dena Zeraatkar ◽

Ariel Izcovich ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Standard Care ◽

Interferon Beta ◽

Meta Analysis ◽

Risk Of Bias ◽

Drug Discontinuation ◽

Duration Of Symptoms ◽

Risk Of Death ◽

The Impact

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Download Full-text

Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

10.1101/2021.07.05.21259867 ◽

2021 ◽

Author(s):

Dena Zeraatkar ◽

Ellen Cusano ◽

Juan Pablo Diaz Martinez ◽

Anila Qasim ◽

Sophia O Mangala ◽

...

Keyword(s):

Systematic Review ◽

Standard Care ◽

Meta Analysis ◽

Analysis Data ◽

Risk Of Bias ◽

Risk Of Death ◽

Study Selection ◽

Receptor Blockers ◽

Meta Analyses ◽

Grade Approach

Objective: To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19. Design: Systematic review and network meta-analysis Data sources: WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses Study selection: Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. Results: We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias 2.0 tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach. We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty). Conclusion: IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.

Download Full-text

Effects of open-label placebos in clinical trials: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-83148-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Melina von Wernsdorff ◽

Martin Loef ◽

Brunna Tuschen-Caffier ◽

Stefan Schmidt

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Medical Condition ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Open Label ◽

Cancer Related Fatigue ◽

Promising Treatment ◽

Irritable Bowel

AbstractOpen-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.

Download Full-text

Association of dyslipidemia with the severity and mortality of coronavirus disease 2019 (COVID-19): a meta-analysis

Virology Journal ◽

10.1186/s12985-021-01604-1 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Yanli Liu ◽

Yilong Pan ◽

Yuyao Yin ◽

Wenhao Chen ◽

Xiaodong Li

Keyword(s):

Fixed Effects ◽

Meta Analysis ◽

Cochrane Library ◽

Case Control Studies ◽

Risk Of Death ◽

Potential Association ◽

Increased Risk ◽

Language Restriction ◽

Newcastle Ottawa Scale

Abstract Background The numbers of confirmed cases of coronavirus disease 2019 (COVID-19) and COVID-19 related deaths are still increasing, so it is very important to determine the risk factors of COVID-19. Dyslipidemia is a common complication in patients with COVID-19, but the association of dyslipidemia with the severity and mortality of COVID-19 is still unclear. The aim of this study is to analyze the potential association of dyslipidemia with the severity and mortality of COVID-19. Methods We searched the PubMed, Embase, MEDLINE, and Cochrane Library databases for all relevant studies up to August 24, 2020. All the articles published were retrieved without language restriction. All analysis was performed using Stata 13.1 software and Mantel–Haenszel formula with fixed effects models was used to compare the differences between studies. The Newcastle Ottawa scale was used to assess the quality of the included studies. Results Twenty-eight studies involving 12,995 COVID-19 patients were included in the meta-analysis, which was consisted of 26 cohort studies and 2 case–control studies. Dyslipidemia was associated with the severity of COVID-19 (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.11–1.44, P = 0.038, I2 = 39.8%). Further, patients with dyslipidemia had a 2.13-fold increased risk of death compared to patients without dyslipidemia (95% CI 1.84–2.47, P = 0.001, I2 = 66.4%). Conclusions The results proved that dyslipidemia is associated with increased severity and mortality of COVID-19. Therefore, we should monitor blood lipids and administer active treatments in COVID-19 patients with dyslipidemia to reduce the severity and mortality.

Download Full-text

Clinical effectiveness of convalescent plasma in hospitalized patients with COVID-19: a systematic review and meta-analysis

Therapeutic Advances in Respiratory Disease ◽

10.1177/17534666211028077 ◽

2021 ◽

Vol 15 ◽

pp. 175346662110280

Author(s):

Roberto Ariel Abeldaño Zuñiga ◽

Ruth Ana María González-Villoria ◽

María Vanesa Elizondo ◽

Anel Yaneli Nicolás Osorio ◽

David Gómez Martínez ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Clinical Improvement ◽

Data Extraction ◽

Meta Analysis ◽

Clinical Effectiveness ◽

Risk Of Bias ◽

Hospitalized Patients ◽

Low Risk ◽

Controlled Clinical Trials

Aims: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. Methods: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. Results: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. Conclusion: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed. The reviews of this paper are available via the supplemental material section.

Download Full-text

Mortality Benefit From the Passive Leg Raise Maneuver in Guiding Resuscitation of Septic Shock Patients: A Systematic Review and Meta-Analysis of Randomized Trials

Journal of Intensive Care Medicine ◽

10.1177/08850666211019713 ◽

2021 ◽

pp. 088506662110197

Author(s):

Moosa Azadian ◽

Suyee Win ◽

Amir Abdipour ◽

Carolyn Krystal Kim ◽

H. Bryant Nguyen

Keyword(s):

Systematic Review ◽

Septic Shock ◽

Fluid Resuscitation ◽

Standard Care ◽

Meta Analysis ◽

Risk Of Bias ◽

Time Interval ◽

Eligibility Criteria ◽

Significant Difference ◽

Passive Leg Raise

Background: Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. Methods: This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. Results: We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. Conclusion: Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.

Download Full-text

The role of cardio-protective agents in breast cancer patients to prevent anthracycline induced cardiotoxicity: a systematic review and network meta-analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.3291 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Jeyaprakash ◽

S Sangha ◽

K Robeldo ◽

K Ellenberger ◽

S Sivapathan ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Ace Inhibitors ◽

Ace Inhibitor ◽

Beta Blockers ◽

Meta Analysis ◽

Risk Of Bias ◽

Breast Cancer Patients ◽

Protective Agents ◽

Cardio Protection

Abstract Background Anthracycline (ANT)-based chemotherapy for breast malignancies have significantly improved cancer outcomes. However, the cardiotoxicity induced by ANTs in the breast cancer population has increased major adverse cardiac events. While randomised controlled trials (RCTs) have explored different primary preventative agents to confer cardio-protection pre chemotherapy, comparisons between agents has been limited. It is unclear which drug is the most efficacious in preserving Left Ventricular Ejection Fraction (LVEF) amongst this population. Purpose To perform a network meta-analysis of RCTs comparing the impact on LVEF of various prophylactic cardio-protective agents, when prescribed to breast cancer patients prior to ANT-based chemotherapy. Methods Two independent authors performed a literature search as per the PRISMA guidelines using four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTS evaluating cardio protective agents. The trial population was limited to patients with breast cancer without prior ANT exposure. Trials were only included if the cardio-protective agents were commenced prior to ANT dosing. The assessed outcome was a mean change in LVEF pre and post ANT dosing, compared to placebo prevention. Extracted data included age, ANT dose, and LVEF pre and post chemotherapy. The Cochrane Risk of Bias tool was used to appraise included RCTs. Results From 2807 search results, we identified twelve RCTs which evaluated 1126 patients. Seven studies assessed beta-blockers alone and two assessed combination ACE inhibitors and beta blockers. Individual studies assessing ACE inhibitors, spironolactone or rosuvastatin alone were also included. All patients were female with an average age of 50.5 and average ANT dose of 412 mg/m2. Our network meta-analysis showed beta-blockers showed significant protection with higher LVEF than placebo by 2.38% [0.52, 4.25]. ACE inhibitors showed a similar magnitude of LVEF preservation 2.59% [−0.20, 5.38] but not statistically significant due to wider CI because of lower sample size (n=250). Spironolactone showed a statistically significant preservation in LVEF by 12.80% [3.44, 22.16], however this was based on a single study (n=83), with marked measurement bias and deviations from intended intervention. All included trials had an intermediate or high risk of bias, with marked heterogeneity in ANT dosing and LVEF monitoring. Conclusion Beta-blockers minimise LVEF decline when administered prior to anthracycline chemotherapy, compared against alternate agents. Data may be underpowered to demonstrate the benefit of ACE inhibitor and combination beta blocker/ACE inhibitor prescription. The quality of RCT data to date is limited by a high risk of bias and significant heterogeneity between RCA reporting. This analysis is likely to inform clinical practice, and allow clinicians to prescribe primary cardio-protection in patients at high risk of cardiotoxicity. Funding Acknowledgement Type of funding source: None

Download Full-text

Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Cancers ◽

10.3390/cancers13092159 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2159

Author(s):

Charalampos Aktypis ◽

Maria-Eleni Spei ◽

Maria Yavropoulou ◽

Göran Wallin ◽

Anna Koumarianou ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Effects ◽

Targeted Therapies ◽

Safety Profile ◽

Meta Analysis ◽

Mtor Inhibitors ◽

Risk Of Bias ◽

Neuroendocrine Neoplasms ◽

Controlled Trials

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.

Download Full-text