Cardiovascular pharmacotherapy: Innovation stuck in translation

Rongen, Gerard A.; Wever, Kimberley E.

doi:10.1016/j.ejphar.2015.03.035

Cited by 12 publications

(8 citation statements)

References 35 publications

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“…This would help to provide a more informed view before proceeding to clinical trials and reduce publication bias [52]. It allows verification of predefined study hypothesis and end-points of the study [53]. …”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

Zheng

Bao

Zhu

et al. 2017

Oxidative Medicine and Cellular Longevity

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Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G-Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10-item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta-analyses showed that G-Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase-MB) when compared with control group (P < 0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST-segment depression were reported in one study (P < 0.05). Additionally, the possible mechanisms of G-Rb1 for myocardial infarction are antioxidant, anti-inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G-Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

Zheng

Bao

Zhu

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…In addition to limitations in internal validity, the external validity of animal studies might be limited by several factors. First, there are important differences in the biology and pathophysiology between animals and humans[ 6 ]. We show that the present body of evidence has been predominantly obtained in rodents, and suggest that replication of these results in other (larger) animal species can increase the confidence in these findings.…”

Section: Discussionmentioning

confidence: 99%

“…These disappointing findings urge a critical reappraisal of the animal studies on which the hypothesis that metformin has direct cardioprotective properties are based. In general, failed translation of preclinical results can be due to limited internal validity of the animal studies, limited external validity, or publication bias [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction

et al. 2017

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Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE’s risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.

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“…aminoglycosides, NSAIDs and inhibitors of the renin-angiotensin-aldosterone system) because clinical trials exploring other strategies to prevent ischemia–reperfusion injury are not conclusive or negative ( Zuk and Bonventre 2015, EL MESSAOUDI et al 2015b, EL MESSAOUDI et al 2015a, ROSS et al 2005 ). Thus, the conclusion is justified that, at least up to now, strategies that prevent ischemia–reperfusion injury in pre-clinical models are stuck in translation to the clinic ( RONGEN and WEVER 2015 ).…”

mentioning

confidence: 99%

“…What is the reason for these disappointments in the clinical development of promising pre-clinical interventions to prevent ischemia–reperfusion injury? First, as reviewed recently, pre-clinical studies in the field of ischemia–reperfusion often have serious methodological flaws, resulting in potential serious bias of results ( RONGEN and WEVER 2015 ). In that regard, we should however compliment Kishi et al for their accurate report of their methodology and findings: some important basic methodological essentials were addressed such as drop-outs, randomization and blinding.…”

mentioning

confidence: 99%

Cardiovascular pharmacotherapy: Innovation stuck in translation

Cited by 12 publications

References 35 publications

Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction

High Dose Meclizine Prevents Renal Ischemia–Reperfusion Injury in Healthy Male Mice

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