scholarly journals Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses

BMJ ◽  
2020 ◽  
pp. l7078 ◽  
Author(s):  
Joshua D Wallach ◽  
Kun Wang ◽  
Audrey D Zhang ◽  
Deanna Cheng ◽  
Holly K Grossetta Nardini ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Systematic Review ◽  
Cardiovascular Risk ◽  
Meta Analysis ◽  
Odds Ratios ◽  
Level Data ◽  
Increased Risk ◽  
Meta Analyses ◽  
Analytical Approaches

AbstractObjectivesTo conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying analytical approaches with three aims in mind: to clarify uncertainties about the cardiovascular risk of rosiglitazone; to determine whether different analytical approaches are likely to alter the conclusions of adverse event meta-analyses; and to inform efforts to promote clinical trial transparency and data sharing.DesignSystematic review and meta-analysis of randomized controlled trials.Data sourcesGlaxoSmithKline’s (GSK’s) ClinicalStudyDataRequest.com for individual patient level data (IPD) and GSK’s Study Register platforms, MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019 for summary level data.Eligibility criteria for selecting studiesRandomized, controlled, phase II-IV clinical trials that compared rosiglitazone with any control for at least 24 weeks in adults.Data extraction and synthesisFor analyses of trials for which IPD were available, a composite outcome of acute myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death was examined. These four events were examined independently as secondary analyses. For analyses including trials for which IPD were not available, myocardial infarction and cardiovascular related death were examined, which were determined from summary level data. Multiple meta-analyses were conducted that accounted for trials with zero events in one or both arms with two different continuity corrections (0.5 constant and treatment arm) to calculate odds ratios and risk ratios with 95% confidence intervals.Results33 eligible trials were identified from ClinicalStudyDataRequest.com for which IPD were available (21 156 patients). Additionally, 103 trials for which IPD were not available were included in the meta-analyses for myocardial infarction (23 683 patients), and 103 trials for which IPD were not available contributed to the meta-analyses for cardiovascular related death (22 772 patients). Among 29 trials for which IPD were available and that were included in previous meta-analyses using GSK’s summary level data, more myocardial infarction events were identified by using IPD instead of summary level data for 26 trials, and fewer cardiovascular related deaths for five trials. When analyses were limited to trials for which IPD were available, and a constant continuity correction of 0.5 and a random effects model were used to account for trials with zero events in only one arm, patients treated with rosiglitazone had a 33% increased risk of a composite event compared with controls (odds ratio 1.33, 95% confidence interval 1.09 to 1.61; rosiglitazone population: 274 events among 11 837 patients; control population: 219 events among 9319 patients). The odds ratios for myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death were 1.17 (0.92 to 1.51), 1.54 (1.14 to 2.09), 1.15 (0.55 to 2.41), and 1.18 (0.60 to 2.30), respectively. For analyses including trials for which IPD were not available, odds ratios for myocardial infarction and cardiovascular related death were attenuated (1.09, 0.88 to 1.35, and 1.12, 0.72 to 1.74, respectively). Results were broadly consistent when analyses were repeated using trials with zero events across both arms and either of the two continuity corrections was used.ConclusionsThe results suggest that rosiglitazone is associated with an increased cardiovascular risk, especially for heart failure events. Although increased risk of myocardial infarction was observed across analyses, the strength of the evidence varied and effect estimates were attenuated when summary level data were used in addition to IPD. Because more myocardial infarctions and fewer cardiovascular related deaths were reported in the IPD than in the summary level data, sharing IPD might be necessary when performing meta-analyses focused on safety.Systematic review registrationOSF Home https://osf.io/4yvp2/.

scholarly journals Updating Insights into Rosiglitazone and Cardiovascular Risk through Shared Data: Individual Patient- and Summary-Level Meta-Analyses

2019 ◽  
Author(s):  
Joshua D Wallach ◽  
Kun Wang ◽  
Audrey D Zhang ◽  
Deanna Cheng ◽  
Holly K Grossetta Nardini ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Systematic Review ◽  
Cardiovascular Risk ◽  
Meta Analysis ◽  
Myocardial Infarctions ◽  
Odds Ratios ◽  
Level Data ◽  
Continuity Corrections ◽  
Meta Analyses

ABSTRACTObjectiveTo conduct a systematic review and meta-analysis of the effects of rosiglitazone therapy on cardiovascular risk and mortality using multiple data sources and varying analytical approaches.DesignSystematic review and meta-analysis of randomized controlled trials.Data sourcesGlaxoSmithKline’s (GSK) Clinical Study Data Request (CSDR) and Study Register platforms, MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019.Study selection criteriaRandomized, controlled, phase II-IV clinical trials comparing rosiglitazone with any control for at least 24 weeks in adults.Data extraction and synthesisFor analyses of trials for which individual patient-level data (IPD) were available, we examined a composite of the following events as our primary outcome: acute myocardial infarction, heart failure, cardiovascular-related deaths, and non-cardiovascular-related deaths. As secondary analyses, these four events were examined independently. When also including trials for which IPD were not available, we examined myocardial infarction and cardiovascular-related deaths, ascertained from summary-level data. Multiple meta-analyses were conducted, accounting for trials with zero events in one or all arms with two different continuity corrections (i.e., 0.5 constant and treatment arm comparator continuity correction), to calculate odds ratios and risk ratios with 95% confidence intervals.ResultsThere were 33 eligible trials for which IPD were available (21156 participants) through GSK’s CSDR. We also identified 103 additional trials for which IPD were not available from which we ascertained myocardial infarctions (23683 patients) and 103 trials for cardiovascular-related deaths (22772 patients). Among trials for which IPD were available, we identified a greater number of myocardial infarctions and fewer cardiovascular-related deaths reported in the IPD as compared to the summary-level data. When limited to trials for which IPD were available and accounting for trials with zero-events in only one arm using a constant continuity correction of 0.5, patients treated with rosiglitazone had a 39% increased risk of a composite event compared with controls (Mantel-Haenszel odds ratio 1.39, 95% CI 1.15 to 1.68). When examined separately, the odds ratios for myocardial infarction, heart failure, cardiovascular-related death, and non-cardiovascular-related death were 1.25 (0.99 to 1.60), 1.60 (1.20 to 2.14), 1.18 (0.64 to 2.17), and 1.13 (0.58 to 2.20), respectively. When all trials for which IPD were and were not available were combined for myocardial infarction and cardiovascular-related deaths, the odds ratios were attenuated (1.13 (0.92 to 1.38) and 1.10 (0.73 to 1.65), respectively). Effect estimates and 95% confidence intervals were broadly consistent when analyses were repeated including trials with zero events across all arms using constant continuity corrections of 0.5 or treatment arm continuity corrections.ConclusionsResults of this comprehensive meta-analysis aggregating a multitude of trials and analyzed using a variety of statistical techniques suggest that rosiglitazone is consistently associated with an increased cardiovascular risk, likely driven by heart failure events, whose interpretation is complicated by varying magnitudes of myocardial infarction risk that were attenuated through aggregation of summary-level data in addition to IPD.Systematic review registrationhttps://osf.io/4yvp2/What is already known on this topic-Since 2007, there have been multiple meta-analyses, using various analytic approaches, that have reported conflicting findings related to rosiglitazone’s cardiovascular risk.-Previous meta-analyses have relied primarily on summary-level data, and did not have access to individual patient-level data (IPD) from clinical trials.-Currently, there is little consensus on which method should be used to account for sparse adverse event data in meta-analyses.What this study adds-Among trials for which IPD were available, rosiglitazone use was consistently associated with an increased cardiovascular risk, likely driven by heart failure events.-Interpretation of rosiglitazone’s cardiovascular risk is complicated by varying magnitudes of myocardial infarction risk that were attenuated through aggregation of summary-level data in addition to IPD.-Among trials for which IPD were available, we identified a greater number of myocardial infarctions and fewer cardiovascular deaths reported in the IPD as compared to the summary-level data, which suggests that IPD may be necessary to accurately classify all adverse events when performing meta-analyses focused on safety.

scholarly journals POS1131 THE INCIDENCE AND PREVALENCE OF CARDIOVASCULAR DISEASES IN GOUT: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 844.2-845
Author(s):  
P. Cox ◽  
S. Gupta ◽  
S. S. Zhao ◽  
D. Hughes
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Venous Thromboembolism ◽  
Cardiovascular Diseases ◽  
Cerebrovascular Accident ◽  
Meta Analysis ◽  
Pooled Prevalence ◽  
Increased Risk

Background:Gout is an inflammatory crystal arthropathy characterised by hyperuricaemia and sodium urate crystal deposition. Both gout and subclinical hyperuricaemia are associated with adverse cardiovascular outcomes. Several studies have found gout to cause an increased risk of cardiovascular disease, but the evidence is not unanimous. The conflicting evidence has made it difficult to establish the extent of the cardiovascular risk to patients with gout.Objectives:To describe the incidence and prevalence of cardiovascular disease in gout, compare these results with non-gout controls.Methods:PubMed, Scopus and Web of Science were systematically searched in January 2021 for studies reporting prevalence of any cardiovascular disease in a gout population. Studies with non-representative sampling, where a cohort had been used in another study, small sample size (< 100) and where gout could not be distinguished from other rheumatic conditions were excluded. Sample size, prevalence of the investigated cardiovascular disease, definition of gout and cardiovascular disease, demographic data, data source and any comparisons with non-gout controls were extracted from each study. Where prevalence data was reported in ≥3 cohorts meta-analysis was performed using random-effect models.Results:Of the 6164 titles identified, 105 full texts were assessed for eligibility with 30 included in the review, producing a gout population of 1,125,988. Pooled prevalence estimates were calculated for six cardiovascular diseases: heart failure (8.73%; 95% confidence interval (CI), 2.85 – 23.76), cerebrovascular accident (4.27%; 95% CI, 1.83 – 9.67), myocardial infarction (2.82%; 95% CI, 1.58 – 5.01), venous thromboembolism (2.05%; 95% CI, 1.22 – 3.43), hypertension (63.94%; 95% CI, 24.51 – 90.64) and cardiovascular mortality (4.75%; 95% CI, 3.56 – 6.31). Twenty studies reported comparisons with non-gout controls, illustrating an increased risk in the gout group across all cardiovascular diseases, particularly for myocardial infarction.Conclusion:Cardiovascular diseases are more prevalent in patients with gout and should prompt vigilance from clinicians to the need to assess and stratify cardiovascular risk. These results are in line with other studies which have shown an increased cardiovascular risk for sufferers of hyperuricaemia, highlighting the need for future research to explain this finding. There are limited studies in the literature investigating less common cardiovascular conditions, illustrating the need for future work if a more thorough picture of prevalence is to be established.Figure 1.Forest plots of pooled prevalence of: (A) 8.73% for heart failure, (B) 4.27% for cerebrovascular accident, (C) 2.82% for myocardial infarction, (D) 2.05% for venous thromboembolism, (E) 63.94% for hypertension and (F) 4.75% for cardiovascular mortality.Disclosure of Interests:None declared.

scholarly journals The incidence and prevalence of cardiovascular diseases in gout: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Peter Cox ◽  
Sonal Gupta ◽  
Sizheng Steven Zhao ◽  
David M. Hughes
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Random Effect ◽  
Small Sample ◽  
Future Research ◽  
Increased Risk

AbstractThe aims of this systematic review and meta-analysis were to describe prevalence of cardiovascular disease in gout, compare these results with non-gout controls and consider whether there were differences according to geography. PubMed, Scopus and Web of Science were systematically searched for studies reporting prevalence of any cardiovascular disease in a gout population. Studies with non-representative sampling, where a cohort had been used in another study, small sample size (< 100) and where gout could not be distinguished from other rheumatic conditions were excluded, as were reviews, editorials and comments. Where possible meta-analysis was performed using random-effect models. Twenty-six studies comprising 949,773 gout patients were included in the review. Pooled prevalence estimates were calculated for five cardiovascular diseases: myocardial infarction (2.8%; 95% confidence interval (CI)s 1.6, 5.0), heart failure (8.7%; 95% CI 2.9, 23.8), venous thromboembolism (2.1%; 95% CI 1.2, 3.4), cerebrovascular accident (4.3%; 95% CI 1.8, 9.7) and hypertension (63.9%; 95% CI 24.5, 90.6). Sixteen studies reported comparisons with non-gout controls, illustrating an increased risk in the gout group across all cardiovascular diseases. There were no identifiable reliable patterns when analysing the results by country. Cardiovascular diseases are more prevalent in patients with gout and should prompt vigilance from clinicians to the need to assess and stratify cardiovascular risk. Future research is needed to investigate the link between gout, hyperuricaemia and increased cardiovascular risk and also to establish a more thorough picture of prevalence for less common cardiovascular diseases.

scholarly journals Prediction of all-cause mortality with malnutrition assessed by controlling nutritional status score in patients with heart failure: a systematic review and meta-analysis

2021 ◽  
pp. 1-8
Author(s):  
Huiyang Li ◽  
Peng Zhou ◽  
Yikai Zhao ◽  
Huaichun Ni ◽  
Xinping Luo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Nutritional Status ◽  
Meta Analysis ◽  
Predictive Values ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Conut Score

Abstract Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure. Design: Systematic review and meta-analysis. Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase. Participants: Ten studies involving 5196 patients with heart failure. Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up. Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.

scholarly journals Platelet function and cardiovascular risk in adult HIV-infected patients on HAART: a protocol for a systematic review and meta-analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e019468 ◽  
Author(s):  
Bongani Brian Nkambule ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Phiwayinkosi Vusi Dludla
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Cardiovascular Risk ◽  
Platelet Activation ◽  
Meta Analysis ◽  
People Living With Hiv ◽  
Qualitative Synthesis ◽  
Cvd Risk ◽  
Increased Risk ◽  
Statistical Heterogeneity

IntroductionThe incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART).MethodsThis will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened; data will be extracted, and a qualitative synthesis will be conducted. Data extraction will be performed using Review Manager V.5.3. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran’s Q statistic and the I2statistics will be used to analyse statistical heterogeneity between studies. If included studies show high levels of homogeneity, a random effects meta-analysis will be performed using R statistical software.Ethics and disseminationThis will be a review of existing studies and will not require ethical approval. The findings will be disseminated through peer-reviewed publication and presented at local and international conferences. An emerging patient management dilemma is that of the increased incidence of CVD in people living with HIV on HAART. This review may inform treatment and cardiovascular risk stratification of HIV-infected patients at increased risk of developing CVD.PROSPERO registration numberCRD42017062393.

Association between depression and increased risk of readmission in patients with heart failure: a systematic review and meta-analysis

2021 ◽  
Vol 69 (4) ◽  
Author(s):  
Jakrin KEWCHAROEN ◽  
Chol TACHORUEANGWIWAT ◽  
Chanavuth KANITSORAPHAN ◽  
Sakditad SAOWAPA ◽  
Nattapat NITINAI ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Meta Analysis ◽  
Increased Risk ◽  
Patients With Heart Failure

scholarly journals Investigating alexithymia in autism: A systematic review and meta-analysis

2019 ◽  
Vol 55 ◽  
pp. 80-89 ◽  
Author(s):  
Emma Kinnaird ◽  
Catherine Stewart ◽  
Kate Tchanturia
Keyword(s):  
Systematic Review ◽  
Emotional Processing ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Autistic People ◽  
Increased Risk ◽  
Popu Lations ◽  
Specific Subgroup ◽  
New Research ◽  
Meta Analyses

AbstractBackground:New research suggests that, rather than representing a core feature of autism spectrum disorder (ASD), emotional processing difficulties reflect co-occurring alexithymia. Autistic individuals with alexithymia could therefore represent a specific subgroup of autism who may benefit from tailored interventions. The aim of this systematic review and meta-analysis was to explore the nature and prevalence of alexithymia in autism using the Toronto Alexithymia Scale (TAS).Methods:Online scientific databases were searched systematically for studies on ASD popu lations using the TAS. Meta-analyses were performed to evaluate differences in scores between the ASD and neurotypical groups, and to determine the prevalence of alexithymia in these populations.Results:15 articles comparing autistic and neurotypical (NT) groups were identified. Autistic people scored significantly higher on all scores compared to the NT group. There was also a higher prevalence of alexithymia in the ASD group (49.93% compared to 4.89%), with a significantly increased risk of alexithymia in autistic participants.Conclusions:This review highlights that alexithymia is common, rather than universal, in ASD, supporting a growing body of evidence that co-occurring autism and alexithymia represents a specific subgroup in the ASD population that may have specific clinical needs. More research is needed to understand the nature and implications of co-occurring ASD and alexithymia.

scholarly journals Natriuretic peptide-guided treatment for heart failure: a systematic review and meta-analysis

2019 ◽  
Vol 25 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Julie McLellan ◽  
Clare R Bankhead ◽  
Jason L Oke ◽  
F D Richard Hobbs ◽  
Clare J Taylor ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Natriuretic Peptide ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Individual Outcomes ◽  
All Cause Mortality ◽  
Registration Number ◽  
Randomised Controlled ◽  
Meta Analyses

BackgroundGUIDE-IT, the largest trial to date, published in August 2017, evaluating the effectiveness of natriuretic peptide (NP)-guided treatment of heart failure (HF), was stopped early for futility on a composite outcome. However, the reported effect sizes on individual outcomes of all-cause mortality and HF admissions are potentially clinically relevant.ObjectiveThis systematic review and meta-analysis aims to combine all available trial level evidence to determine if NP-guided treatment of HF reduces all-cause mortality and HF admissions in patients with HF.Study selectionEight databases, no language restrictions, up to November 2017 were searched for all randomised controlled trials comparing NP-guided treatment versus clinical assessment alone in adult patients with HF. No language restrictions were applied. Publications were independently double screened and extracted. Fixed-effect meta-analyses were conducted.Findings89 papers were included, reporting 19 trials (4554 participants), average ages 62–80 years. Pooled risk ratio estimates for all-cause mortality (16 trials, 4063 participants) were 0.87, 95% CI 0.77 to 0.99 and 0.80, 95% CI 0.72 to 0.89 for HF admissions (11 trials, 2822 participants). Sensitivity analyses, restricted to low risk of bias, produced similar estimates, but were no longer statistically significant.ConclusionsConsidering all the evidence to date, the pooled effects suggest that NP-guided treatment is beneficial in reducing HF admissions and all-cause mortality. However, there is still insufficient high-quality evidence to make definitive recommendations on the use of NP-guided treatment in clinical practice.Trial registration numberSystematic Review Cochrane Database Number: CD008966.

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