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

BMJ ◽  
2021 ◽  
pp. n1302
Keyword(s):  
Cardiovascular Risk ◽  
Shared Data ◽  
Meta Analyses

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 Sex Disparities in Cardiovascular Risk Factor Assessment and Screening for Diabetes-Related Complications in Individuals With Diabetes: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Marit de Jong ◽  
Sanne A. E. Peters ◽  
Rianneke de Ritter ◽  
Carla J. H. van der Kallen ◽  
Simone J. S. Sep ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Smoking Status ◽  
Sex Disparities ◽  
Meta Analyses ◽  
Number Of Individuals ◽  
To Receive ◽  
Substantial Heterogeneity

BackgroundInsight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study whether sex disparities exist in the assessment of cardiovascular risk factors and screening for diabetes-related complications.MethodsPubMed was systematically searched up to April 2020, followed by manual reference screening and citations checks (snowballing) using Google Scholar. Observational studies were included if they reported on the assessment of cardiovascular risk factors (HbA1c, lipids, blood pressure, smoking status, or BMI) and/or screening for nephropathy, retinopathy, or performance of feet examinations, in men and women with diabetes separately. Studies adjusting their analyses for at least age, or when age was considered as a covariable but left out from the final analyses for various reasons (i.e. backward selection), were included for qualitative analyses. No meta-analyses were planned because substantial heterogeneity between studies was expected. A modified Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess risk of bias.ResultsOverall, 81 studies were included. The majority of the included studies were from Europe or North America (84%).The number of individuals per study ranged from 200 to 3,135,019 and data were extracted from various data sources in a variety of settings. Screening rates varied considerably across studies. For example, screening rates for retinopathy ranged from 13% to 90%, with half the studies reporting screening rates less than 50%. Mixed findings were found regarding the presence, magnitude, and direction of sex disparities with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, with some evidence suggesting that women, compared with men, may be more likely to receive retinopathy screening and less likely to receive foot exams.ConclusionOverall, no consistent pattern favoring men or women was found with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, and screening rates can be improved for both sexes.

scholarly journals Maternal diabetes during pregnancy and carotid intima-media thickness in children

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Chiolero ◽  
A Epure ◽  
M Rios-Leyvraz ◽  
D Anker ◽  
Y Mivelaz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Maternal Diabetes ◽  
Small Sample ◽  
Primordial Prevention ◽  
Media Thickness ◽  
Mean Differences ◽  
Meta Analyses

Abstract Background Cardiovascular risk over the life course may be related to intrauterine risk factors, for instance, the exposure to maternal diabetes. Our objective was to systematically review studies that assessed the association of maternal diabetes during pregnancy and carotid-intima media thickness (CIMT), a marker of cardiovascular risk, in children. Methods We followed methods outlined in a published protocol for a systematic review on risk factors and determinants of CIMT in children (PROSPERO registration: CRD42017075169). Standardized mean differences in CIMT between offspring of women with and without diabetes during pregnancy were computed. Random effects meta-analyses were performed. The reliability of CIMT measurements was assessed. Funding SNSF 32003B-163240. Results Three observational studies involving 658 children were retained. Two studies were conducted in Europe and one in Australia. Age at CIMT assessment ranged from 2 days to 8 years. Two studies evaluated gestational diabetes during pregnancy and found no difference in CIMT among exposed children compared to controls (0.00 (95% CI: -0.41 to 0.41); 0.00 (95% CI; -0.28 to 0.28)). One study, that did not specify the type of diabetes evaluated, identified a higher CIMT (0.46 (95% CI; -0.07 to 1.00)). The pooled standardized mean difference in CIMT between offspring of women with and without diabetes during pregnancy was 0.08 (95% CI: -0.16 to 0.33; I2: 17.1%). Conclusions Overall, there is no clear association between maternal diabetes during pregnancy and offspring's CIMT. The degree of confidence in results is limited by the low number of studies, with relatively small sample sizes and a low number of participants exposed to maternal diabetes. Key messages Children exposed to maternal diabetes have no substantial alterations in vascular structure. More research is needed to inform primordial prevention of cardiovascular disease among these children.

Nonselective Nonsteroidal Antiinflammatory Drugs and Cardiovascular Risk: Are They Safe?

2007 ◽  
Vol 41 (7-8) ◽  
pp. 1163-1173 ◽  
Author(s):  
Javier C Waksman ◽  
Aaron Brody ◽  
Scott D Phillips
Keyword(s):  
Cardiovascular Risk ◽  
Significant Risk ◽  
Case Control ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Double Blind Study ◽  
Case Control Studies ◽  
Antiinflammatory Drugs ◽  
Double Blind ◽  
Nsaid Treatment ◽  
Meta Analyses

Objective: To assess possible cardiovascular risks associated with use of nonselective nonsteroidal antiinflammatory drugs (NSAIDs). Data Sources: Medline and Embase were searched from January 1985 through April 2007 and relevant studies were retrieved. Study Selection and Data Extraction: Peer-reviewed, prospective, double-blind, case–control, and cohort-design studies published in the English language literature were considered eligible for review. Previous meta-analyses and systematic reviews were also analyzed. In total, 17 case–control studies; 9 cohort studies; 1 prospective, double-blind study; 3 meta-analyses; and 1 systematic review of observational studies were identified. Data Synthesis: Three studies were prospective and the remainder consisted of observational, retrospective studies, with most reporting acute fatal or nonfatal myocardial infarction as the cardiovascular endpoint. Among the nonselective NSAIDs, diclofenac appears to pose the highest risk for cardiovascular toxicity; other agents trend toward a neutral effect with respect to cardiovascular risk. Although the data are suggestive, it remains unclear whether naproxen provides protective cardiovascular effects among patients on chronic therapy. Conclusions: Currently available data are insufficient for defining evidence-based clinical guidelines for the use of NSAIDs, and the need for additional research, specifically randomized controlled trials, is evident. Diclofenac demonstrates a significant risk while naproxen appears to pose the lowest, albeit nonsignificant, risk for cardiovascular morbidity. Although the current clinical evidence may not warrant recommending naproxen as the preferred NSAID treatment, it may be prudent to avoid diclofenac for patients with cardiovascular risk factors requiring NSAID treatment.

scholarly journals Physicians’ Appraisal and Response to Early Evidence on Cardiovascular Risk Associated with Rosiglitazone: Knowledge Translation in Clinical Practice

2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Garielle E. Brown ◽  
Adriane M. Lewin MSc ◽  
Michael A. De Souza BSc ◽  
Alun L Edwards MD ◽  
William A. Ghali MD MPH ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiovascular Risk ◽  
Knowledge Translation ◽  
Meta Analysis ◽  
Oral Hypoglycemic Agent ◽  
High Profile ◽  
Hypoglycemic Agent ◽  
Early Evidence ◽  
Meta Analyses

In 2007, a high-profile meta-analysis raised concerns about the safety of rosiglitazone, a thenpopular oral hypoglycemic agent. In this study, the authors describe how physicians accessed, evaluated, and applied this information clinically. Their findings showed that although a highly publicized meta-analysis raised concerns among physicians, meta-analyses can be challenging to interpret. Efforts are needed to improve the understanding of this methodology to aid physicians in translating results into practice.

scholarly journals The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications

2019 ◽  
Vol 91 (8) ◽  
pp. 118-126 ◽  
Author(s):  
O D Ostroumova ◽  
A I Kochetkov ◽  
A P Pereverzev ◽  
E V Kravchenko ◽  
A N Kazjulin ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Drug Interactions ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cardiovascular Events ◽  
Cardiovascular Complications ◽  
Inclusion Criteria ◽  
Combined Use ◽  
Meta Analyses ◽  
The Relationship

In the article the problem of the combined use of clopidogrel and various proton pump inhibitors (PPIs) in terms of cardiovascular complications risk and stent thrombosis is considered. The results of meta - analyses and a systematic reviews affecting this issue are represented in detail. The inter - drug interactions mechanisms of various PPIs with clopidogrel based on the characteristics of the metabolism in the liver cytochromes system are discussed. The authors conducted a search, systematization and analysis of studies regarding the association between cardiovascular risk and combined use of individual medications from PPI class with clopidogrel, and these results are presented in the review. Currently available data do not allow to answer the question about the differences between individual PPIs in their impact on the risk of adverse cardiovascular events due to the small number of such studies, design heterogeneity, differences in the inclusion criteria and end points as well as in the rate of administration of individual PPIs.

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