Restrictive Filling Pattern is a Powerful Predictor of Heart Failure Events Postacute Myocardial Infarction and in Established Heart Failure: A Literature-Based Meta-Analysis

Abstract Context The goal of the meta-analysis was to evaluate the effect of pioglitazone on the primary and secondary prevention of cardiovascular diseases (CVDs) and renal adverse events in patients with or at high risk of type 2 diabetes mellitus (T2DM). Design Randomized controlled trials (RCTs) comparing pioglitazone with any control were identified through PubMed, Embase, and the Cochrane Library. Cardiovascular outcomes included major adverse cardiovascular events (MACEs, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), hospitalization for heart failure, and all-cause mortality. Renal outcomes included change in urinary albumin to creatinine ratio and 24-hour urinary protein excretion. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence intervals (CIs) were pooled. Results A total of 26 studies with 19 645 participants were enrolled. Pioglitazone reduced the risk of MACE (RR, 0.8 [95% CI, 0.7–0.9]), with benefit only seen in patients with a history of established CVDs (0.8 [0.7–0.9]) and not in those without (1.0 [0.7–1.3]). Regarding the individual components, pioglitazone reduced the risk of nonfatal myocardial infarction (0.8 [0.6–1.0]) and nonfatal stroke (0.8 [0.7–0.9]), which was confined to patients with a history of established CVDs, whereas no treatment effect was found on cardiovascular death (1.0 [0.7–1.2]) regardless of the presence of established CVDs. Pioglitazone increased the risk of hospitalization for heart failure (1.3 [1.1–1.6]) and had no treatment effect on all-cause mortality (1.0 [0.8–1.1]). Pioglitazone reduced albuminuria by 18.5% (WMD 18.5% [95% CI, 21.1-16.0]), with a similar benefit in patients with different renal function categories. Conclusions Pioglitazone should be considered in patients with or at high risk of T2DM for the prevention of cardiovascular endpoints, especially in those with a history of established CVD who might benefit the most. Robust reductions in progression of renal disease are seen regardless of baseline renal function degree.

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

BMJ ◽

10.1136/bmj.l7078 ◽

2020 ◽

pp. l7078 ◽

Cited By ~ 12

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/.

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Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials

The Lancet ◽

10.1016/s0140-6736(97)05281-1 ◽

1997 ◽

Vol 350 (9089) ◽

pp. 1417-1424 ◽

Cited By ~ 404

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Congestive Heart Failure ◽

Meta Analysis ◽

Individual Data ◽

Randomised Trials

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Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition

Cardiovascular Research ◽

10.1093/cvr/cvy145 ◽

2018 ◽

Vol 114 (11) ◽

pp. 1445-1461 ◽

Cited By ~ 30

Author(s):

Mona Panahi ◽

Angelos Papanikolaou ◽

Azam Torabi ◽

Ji-Gang Zhang ◽

Habib Khan ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Systematic Review ◽

Clinical Trials ◽

Meta Analysis

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The importance of evidence assessment: Reanalyzing a Meta-analysis on the effect of Prophylactic Amiodarone, on Mortality after Acute Myocardial Infarction and Congestive Heart Failure.

10.47449/cm.2020.1.1.26 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Arturo Martí-Carvajal ◽

Cristina Martí-Amarista

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Congestive Heart Failure ◽

Meta Analysis ◽

Insuficiencia Cardiaca

La amiodarona es un medicamento anti arrítmico que se usa como profilaxis después de un infarto agudo de miocardio (IM) y en pacientes con insuficiencia cardíaca congestiva (ICC). Este estudio tiene como objetivo reevaluar los beneficios y daños clínicos de la amiodarona en pacientes con IM y CHF, según los datos del estudio Amiodarone Trials Meta-Analysis Investigators (ATMAI). Con este objetivo, realizamos un nuevo análisis de ATMAI donde dos autores extrajeron la información de los ensayos incluidos de forma independiente; y otros dos autores comprobaron la veracidad de la información. De los 13 ensayos incluidos (6553 pacientes), ocho ensayos (5101 pacientes) se realizaron en pacientes con IM y cinco ensayos (1452 pacientes) se realizaron en pacientes con ICC. En general, la evidencia fue de baja a modesta, para todos los resultados debido al sesgo (principalmente selección y deserción) y la imprecisión. Para los pacientes con IM, la amiodarona mostró un mayor riesgo de efectos secundarios (RR 1,72; IC del 95%: 1,32 a 2,25 I2: 74%) sin beneficio alguno en la disminución del riesgo de mortalidad por todas las causas (RR 0,87; IC del 95%: 0,69 a 1,1 I2: 40%) en comparación con el placebo o ningún tratamiento. La amiodarona, sin embargo, se asoció con un menor riesgo de mortalidad cardíaca (RR 0,83; IC del 95%: 0,7 a 0,99 I2: 0%) en comparación con placebo o ningún tratamiento. Para los pacientes con ICC, no hubo diferencias entre la amiodarona y el placebo o ningún tratamiento, con respecto a la mortalidad por todas las causas (RR0,86; IC del 95%: 0,71 a 1,04 I2: 26%) y la mortalidad cardíaca (RR 0,82; IC del 95%: 0,64 a 1,04 I2 : 24%). Por tanto, nuestros resultados no apoyan las conclusiones de ATMAI con respecto al efecto beneficioso de la amiodarona en la disminución de la mortalidad en pacientes con IM o ICC. La amiodarona se asoció más bien, con un alto riesgo de eventos adversos en personas con IM. El análisis secuencial de ensayos mostró que no se necesitan más ensayos.

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

10.1101/19000463 ◽

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.

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