scholarly journals Investigating the stratified efficacy and safety of pharmacological blood pressure-lowering: an overall protocol for individual patient-level data meta-analyses of over 300 000 randomised participants in the new phase of the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC)

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e028698 ◽  
Author(s):  
Kazem Rahimi ◽  
Dexter Canoy ◽  
Milad Nazarzadeh ◽  
Gholamreza Salimi-Khorshidi ◽  
Mark Woodward ◽  
...  

IntroductionPrevious research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct individual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment.Methods and analysisRCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for individual meta-analyses will be developed and registered on public platforms.Ethics and disseminationEthics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BP-lowering on important, but less well understood, outcomes, such as new-onset diabetes and renal disease. Findings will be published in peer-reviewed medical journals on behalf of the collaboration.

Author(s):  
Mattias Brunström ◽  
Costas Thomopoulos ◽  
Bo Carlberg ◽  
Reinhold Kreutz ◽  
Giuseppe Mancia

Systematic reviews and meta-analyses are often considered the highest level of evidence, with high impact on clinical practice guidelines. The methodological literature on systematic reviews and meta-analyses is extensive and covers most aspects relevant to the design and interpretation of meta-analysis findings in general. Analyzing the effect of blood pressure–lowering on clinical outcomes poses several challenges over and above what is covered in the general literature, including how to combine placebo-controlled trials, target-trials, and comparative studies depending on the research question, how to handle the potential interaction between baseline blood pressure level, common comorbidities, and the estimated treatment effect, and how to consider different magnitudes of blood pressure reduction across trials. This review aims to address the most important methodological considerations, to guide the general reader of systematic reviews and meta-analyses within our field, and to help inform the design of future studies. Furthermore, we highlight issues where published meta-analyses have applied different analytical strategies and discuss pros and cons with different strategies.


2016 ◽  
Vol 84 (1-2) ◽  
Author(s):  
Enrico Mossello ◽  
David Simoni

<p>High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment. </p><p><strong>Riassunto</strong></p><p>Ipertensione arteriosa e decadimento cognitivo spesso coesistono in età avanzata, sebbene la loro associazione sia complessa dal punto di vista fisiopatologico. Diversi studi longitudinali hanno mostrato che elevati valori pressori in età adulta rappresentano un fattore di rischio per decadimento cognitivo e demenza, sebbene tale associazione sia molto meno chiara in età avanzata. L’effetto della terapia antiipertensiva è risultato ai limiti della significatività statistica nel ridurre il rischio di demenza negli studi di intervento su soggetti anziani, in parte a causa della durata insufficiente del follow-up. D’altra parte, l’insorgenza di demenza è associata con una riduzione dei valori pressori, probabilmente secondaria alla neurodegenerazione. L’effetto prognostico dei valori pressori in anziani con decadimento cognitivo non è stato ancora chiarito, in presenza di un possibile effetto dannoso di un trattamento antiipertensivo aggressivo in questa categoria di pazienti. Un breve screening cognitivo, associato con una semplice valutazione motoria, è raccomandato per identificare gli anziani fragili, che necessitano di un approccio più cauto alla terapia antiipertensiva. I risultati del monitoraggio della pressione arteriosa nelle 24 ore sembrano più utili della misurazione clinica per predire la prognosi degli anziani cognitivamente compromessi. Studi futuri dovrebbero identificare gli obiettivi pressori più appropriati nel trattamento di anziani con decadimento cognitivo.</p>


2019 ◽  
Vol 37 (8) ◽  
pp. 1567-1573 ◽  
Author(s):  
Abdul Salam ◽  
Emily R. Atkins ◽  
Benjumin Hsu ◽  
Ruth Webster ◽  
Anushka Patel ◽  
...  

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