Globalization of heart failure clinical trials: a systematic review of 305 trials conducted over 16 years

Vaduganathan, Muthiah; Tahhan, Ayman Samman; Greene, Stephen J.; Okafor, Maureen; Kumar, Sonali; Butler, Javed

doi:10.1002/ejhf.1130

Cited by 19 publications

(20 citation statements)

References 9 publications

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“…Cardiomyocyte apoptosis during the I/R process is responsible for multiple sequelae of myocardial infarction, including congestive heart failure, cardiac rupture and ventricular arrhythmia (27,28). In the present study, the cardioprotective effect of YB1 in the prevention and control of I/R-derived cardiac damage was evaluated in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3

Wang

et al. 2019

Mol Med Report

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Oxidative stress serves important roles in cardiac injury during the process of ischemia/reperfusion (I/R). Y-box protein 1 (YB1), a member of the highly conserved Y-box protein family, is closely associated with inflammation and stress responses by regulating gene transcription, RNA splicing and mRNA translation. However, the roles of YB1 in oxidative stress-induced myocardial-I/R (M-I/R) injury are unknown. The aim of the present study was to examine the effects of YB1 on H 2 O 2 -induced cardiomyocyte injury and its underlying mechanism. The results demonstrated that YB1 expression was upregulated during H 2 O 2 -induced myocardial injury. YB1 knockdown through transfection of small interfering RNA significantly aggravated cardiac cell apoptosis. Furthermore, YB1 knockdown significantly reversed the H 2 O 2 -mediated increase in phosphorylated signal transducer and activator of transcription (STAT)3, but did not affect the phosphorylation of P38, extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinases, P65, Janus kinase 1 and 2 or STAT1. Moreover, protein co-immunoprecipitation and RNA-binding protein immunoprecipitation assays revealed that YB1 interacted with protein inhibitor of activated STAT 3 (PIAS3) mRNA but not its translated protein. YB1 overexpression may have promoted PIAS3 mRNA decay, decreasing PIAS3 protein levels, and therefore increased the levels of phosphorylated STAT3. Finally, YB1 knockdown, mediated by a lentivirus carrying YB1 targeted short hairpin RNA, significantly decreased left ventricle percentage fractional shortening and ejection fraction values, while increasing the infarct sizes in a rat model of M-I/R injury. These results demonstrated for the first time (to the best of our knowledge) that YB1 may protect cardiac myocytes against H 2 O 2 or M-I/R-induced injury by binding to PIAS3 mRNA and resulting in the phosphorylation of STAT3.

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Section: Discussionmentioning

confidence: 99%

YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3

Wang

et al. 2019

Mol Med Report

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“…The primary region of enrolment for almost half of contemporary HF trials lays outside WE and NA . A meta‐analysis of 300 trials showed that the proportion of trials having their primary region of enrolment in NA or WE decreased from almost 70% to just over 50% within a decade . An important driver of this trend is the greater efficiency of trial enrolment (higher rate of enrolment per centre) in EE and LA .…”

Section: Socioeconomic Determinants As Drivers Of Enrolment and Outcomesmentioning

confidence: 99%

“…61 An important driver of this trend is the greater efficiency of trial enrolment (higher rate of enrolment per centre) in EE and LA. 30,31,61,62 In the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) programme, sites from LA (20 patients per site) and EE (20 patients per site) enrolled more than twice the number of patients per site than those from NA (seven patients per site) and WE (eight patients per site). 62 Similar differences were seen in the ASCEND-HF and ASTRONAUT trials 29,31 (Figure 1).…”

Section: Socioeconomic Determinants Driving Enrolment Of Trialsmentioning

confidence: 99%

“…A meta‐analysis of 300 trials showed that the proportion of trials having their primary region of enrolment in NA or WE decreased from almost 70% to just over 50% within a decade . An important driver of this trend is the greater efficiency of trial enrolment (higher rate of enrolment per centre) in EE and LA . In the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) programme, sites from LA (20 patients per site) and EE (20 patients per site) enrolled more than twice the number of patients per site than those from NA (seven patients per site) and WE (eight patients per site) .…”

Section: Socioeconomic Determinants As Drivers Of Enrolment and Outcomesmentioning

confidence: 99%

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Heart failure around the world

Tromp

Ferreira

Janwanishstaporn

et al. 2019

European J of Heart Fail

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With increasingly large sample sizes required to demonstrate event reduction, heart failure outcome trials are no longer being performed in a small group of selected patients and countries, but at a global scale with worldwide contribution of patients from countries with considerable differences in background therapy, socioeconomic status and healthcare practices. Recent studies have highlighted how socioeconomic determinants rather than geographical factors may underlie the heterogeneity of patient populations across the globe. Therefore, in this review, we evaluated (i) regional differences in patient characteristics and outcomes in recent epidemiologic studies; (ii) regional differences in worldwide representativeness of clinical trial populations; and (iii) the role of socioeconomic determinants in driving country differences in heart failure trial enrolment and clinical outcomes.

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“…1,2 The cost of conducting clinical trials has also continued to rise, promoting migration of trials away from the US. 3 These challenges threaten our ability to reliably generate timely information on important therapies. In addition to delaying completion, variation in enrollment can reduce the power of clinical trials to answer questions.…”

Section: Introductionmentioning

confidence: 99%

Why Do Patients Decline Heart Failure Trials, and What Should We Do About It?

Shore

Speight

Kelkar

et al. 2019

Preprint

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Background: Low patient enrollment in randomized clinical trials (RCTs) escalates costs, leads to under-representation of real-world patient populations, and delays generation of knowledge. Limited data exists on why patients decline participation in RCTs and what factors may lead to increased participation rates. Methods: In-person and telephone interviews were conducted with 19 patients with congestive heart failure who declined participation in RCTs. Interviews were conducted using a structured interview guide. Interviews were transcribed verbatim, and qualitative descriptive analysis was performed. Results: Participants’ median age was 63 years (IQR 51.5-69), 42% were female, and 53% were Black or African-American. Only 6 participants could accurately describe the intervention and clearly understood design of the trial in which they were asked to participate. Most participants made the decision not to participate quickly; only 1 participant took time to deliberate. The most common reasons for not participating were concern for adverse events from the intervention being studied (n=15) and perception of participation being too burdensome (n=10). The most common suggestion provided to increase participant recruitment was involving primary care physicians or cardiologists known to the patients. Conclusion: These findings suggest that patients often decide not to participate in clinical trials quickly, with relatively minimal understanding of the trial. Reasons for declining were heterogeneous, but the most common suggestions for improvement were engaging physicians known to them in the process of recruitment and making participation less burdensome. Addressing these issues may reduce barriers to participation and enhance respect for patients.

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Globalization of heart failure clinical trials: a systematic review of 305 trials conducted over 16 years

Cited by 19 publications

References 9 publications

YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3

YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3

Heart failure around the world

Why Do Patients Decline Heart Failure Trials, and What Should We Do About It?

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