BPLTTC

Blood Pressure Lowering Treatment Trialists' Collaboration







Background

The BPLTTC was conceived and initiated in 1995 as a collaboration between the Principal Investigators of all the major ongoing clinical trials of blood pressure lowering agents. Although previous cycles of BPLTTC have clarified the benefits and risks of blood pressure lowering, significant uncertainties of the benefits and risks of blood pressure lowering remain. The current cycle of the BPLTTC has substantially extended the collaboration to over a quarter million individual participant data with all available baseline and outcome data. This will help to reduce may of the remaining uncertainties about the safety and efficacy of blood pressure lowering treatment.

GOVERNANCE

This current cycle (or phase) of the collaboration is coordinated by the George Institute for Global Health at Oxford. Its work is governed by a Steering Committee which consists of the Director of BPLTTC, Kazem Rahimi, as well as select Principal Investigators of some of the largest trials included in the BPLTTC. The Steering Committee is responsible for the general oversight of the BPLTTC, providing scientific leadership regarding all aspects of the proposal development, analysis, interpretation and reporting. A wide network of collaborators contributes to all scientific activities and debates.

Funding

BPLTTC was initially supported by grants from the pharmaceutical industry, including Astra Hassle AB, Bayer AG, British Heart Foundation, Bristol-Myers Squibb Company, Glaxo Wellcome, Hoechst Marion Roussel, Knoll AG, Merck and Company, Pfizer Inc., Searle, and Institut de Recherches Internationales Servier. Since 2005, BPLTTC has not been funded by the pharmaceutical industry and has only been supported by peer reviewed sources, such as the National Health and Medical Research Council of Australia and the UK National Institute for Health Research.

Projects

Blood pressure lowering in the context of regression to the mean

Status: Draft manuscript
18 March 2017

Systematic reviews of observational studies have quantified regression to the mean in the general population and showed that usual BP has a much narrower distribution than baseline BP. This project quantifies the contribution of regression to the mean to long-term BP changes in clinical trials, and assesses treatment effects by control group usual BP.

Proportional effects of BP lowering treatment on serious vascular events by baseline BP levels, age and by disease status at baseline

Status: Protocol development
26 October 2016

The largest tabular meta-analysis of BP trials has recently suggested similar proportional benefits of BP lowering at different baseline trial-level BP for a range of CVD outcomes but uncertainty remains whether this is true for all patient subgroups. Furthermore, tabular meta-analyses are unable stratify by baseline BP at an individual level and to control for competing events. A detailed IPD meta-analysis will provide a more in depth examination of BP lowering at different baseline levels results and the different proportional effects on CVD outcomes. Furthermore, this will help to ascertain whether certain drug classes have particularly strong positive or negative effects in specific patient subgroups.

Proportional effects of BP lowering on total risk of serious adverse events, by baseline BP levels, age and by disease status at baseline

Status: Protocol development
26 October 2016

Although some BP lowering trials have shown that more intensive lowering is associated higher risk of SAEs as less intensive lower. However, this has not been investigated in detail across the whole spectrums of BP levels and by other important patient features. A detailed IPD meta-analysis will help to address the question of safety of BP lowering overall, by BP levels at baseline, age and disease status.

BP lowering treatment on risk of cancer overall and by class of drug

Status: Protocol development
26 October 2016

Observational evidence suggests BP lowering is associated with a lower risk of non-vascular mortality. However, whether this is causal or due to event misclassification is uncertain. Conflicting meta-analyses have suggested angiotensin receptor blockers increase the risk of cancer and have no effect on cancer. A large-scale IPD meta-analysis will help to provide important evidence on BP lowering effects on cancer risk overall and by drug classes.

Proportional effects of BP lowering on risk of new-onset diabetes, overall and by class of drug

Status: Protocol development
26 October 2016

Observational studies have shown a clear and strong association between elevated BP and future risk of diabetes. Meta-analysis of randomised trials, on the other hand, have indicated that beta-blocker and diuretic use is associated with an increased risk of new onset diabetes and that RAS inhibitor use is associated with a decreased risk of new onset diabetes. However, it is unclear if BP lowering (with either RAS inhibitor or CCB) reduces the risk of new onset diabetes or if prevention of incident diabetes is a class effect.

Proportional effects of BP lowering on risk of new-onset fractures, overall and by class of drug

Status: Protocol development
26 October 2016

Some observational analyses have suggested that initiation of BP lowering therapy is associated with an increased risk of fractures. However, these analyses are susceptible to confounding (sicker elderly patients being initiated on BP lowering medication). In contrast, an analysis of HYVET indicated that BP lowering in the elderly reduced the rate of fractures. An IPD meta-analysis will investigate the effect of antihypertensive therapy on falls/fractures in more detail.

Proportional effects of BP lowering on risk of new-onset dementia, overall and by class of drug

Status: Protocol development
26 October 2016

Observational evidence suggests elevated BP is associated with an increased risk of dementia. However, a meta-analysis of randomised trials found no effect of BP lowering on risk of dementia, but was underpowered to detect a difference. In this project, we explore the effect of BP lowering on risk of dementia.

Proportional effects of BP lowering on risk of atrial fibrillation, overall, by risk of cardiovascular disease and by class of drug.

Status: Protocol development
26 October 2016

Elevated BP is a risk factor for incident atrial fibrillation (AF). However, in a tabular meta-analysis, BP lowering was not associated with a decreased risk of AF outside heart failure patients. This meta-analysis was limited by the small number of incident AF events in non-heart disease populations. Use of individual patient data with more AF events will allow for a reliable determination of whether BP lowering reduces the risk of AF.

More than 250,000 patients

With > 250,000 patients enrolled in the program, the BPLTTC is the largest single database of randomized individual patient data.

Contributing Trials

ALLHAT
ONTARGET
INVEST
PRoFESS
ASCOT
HOT
MRC-1
CONVINCE
VALUE
CHIEF
EUROPA
ACCOMPLISH
ADVANCE
CAPPP
HDFP
NORDIL
FEVER

NAVIGATOR
HOPE
LIFE
ACTIVE I
ALTITUDE
PEACE
ACTION
STOP2
INSIGHT
IPPSH
PROGRESS
ANBP2
TRANSCEND
PATS
DREAM
COLM
SCOPE

DIABHYCAR
SHEP
ACCORD
CASE-J
Syst-Eur
ROADMAP
JATOS
MRC-2
HYVET
HOMED-BP
COPE
Australian TTMH (ANBP - 1983)
VALISH
MultiCentre Int
SPS3
LIT

Syst-China
ELSA
BBB
Hunan province
HIJ-CREATE
DIRECT PROTECT 1
DIRETCT PROTECT 2
SHELL
QUIET
IDNT
JMIC-B
STONE
E-COST
STOP
RENAAL
Dutch TIA
VA NEPHRON-D

PREVENDIT
DIRECT PREVENT 1
MOSES
CAMELOT
BENEDICT
OSCAR
UKPDS
Cardio-Sis
Taylor
AASK
VANHLBI
PHARAO
TOMHS
HEP
MIDAS
EWPHE
NICOLE

PREVENT
APSIS
TROPHY
BCAPS
Oslo
Wei
PART-2
VHAS
ABCD-2
ABCD-1
SCAT
NICS-EH
USPHS

Steering Committee

Barry Davis

Carl Pepine

John Chalmers

Teo Koon

Kazem Rahimi

Publications

Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data

Blood Pressure Lowering Treatment Trialists' Collaboration., Kunal N. Karmali, Donald M. Lloyd-Jones, Joep van der Leeuw, David C. Goff Jr., Salim Yusuf, Alberto Zanchetti, Paul Glasziou, Rodney Jackson, Mark Woodward, Anthony Rodgers, Bruce C. Neal, Eivind Berge, Koon Teo
PLoS medicine 2018, 15(3).

Effects of blood pressure lowering on cardiovascular risk according to baseline body-mass index: a meta-analysis of randomised trials.

Blood Pressure Lowering Treatment Trialists' Collaboration., Ying A, Arima H, Czernichow S, Woodward M, Huxley R, Turnbull F, Perkovic V, Neal B.
Lancet. 2015 Mar 7;385(9971):867-74. doi: 10.1016/S0140-6736(14)61171-5. Epub 2014 Nov 4.

Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data.

Blood Pressure Lowering Treatment Trialists' Collaboration., Sundström J, Arima H, Woodward M, Jackson R, Karmali K, Lloyd-Jones D, Baigent C, Emberson J, Rahimi K, MacMahon S, Patel A, Perkovic V, Turnbull F, Neal B.
Lancet. 2014 Aug 16;384(9943):591-8. doi: 10.1016/S0140-6736(14)61212-5.

Authors' reply to Ladapo and Ogedegbe.

Ninomiya T, Perkovic V; Blood Pressure Lowering Treatment Trialists’ Collaboration.
BMJ. 2014 Jan 15;348:g148. doi: 10.1136/bmj.g148. No abstract available.

Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials.

Blood Pressure Lowering Treatment Trialists' Collaboration., Ninomiya T, Perkovic V, Turnbull F, Neal B, Barzi F, Cass A, Baigent C, Chalmers J, Li N, Woodward M, MacMahon S.
BMJ. 2013 Oct 3;347:f5680. doi: 10.1136/bmj.f5680. Review.

The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline blood pressure: meta-analysis of randomized trials.

Czernichow S, Zanchetti A, Turnbull F, Barzi F, Ninomiya T, Kengne AP, Lambers Heerspink HJ, Perkovic V, Huxley R, Arima H, Patel A, Chalmers J, Woodward M, MacMahon S, Neal B; Blood Pressure Lowering Treatment Trialists' Collaboration.
J Hypertens. 2011 Jan;29(1):4-16. doi: 10.1097/HJH.0b013e32834000be.

Do men and women respond differently to blood pressure-lowering treatment? Results of prospectively designed overviews of randomized trials.

Turnbull F, Woodward M, Neal B, Barzi F, Ninomiya T, Chalmers J, Perkovic V, Li N, MacMahon S; Blood Pressure Lowering Treatment Trialists' Collaboration.
Eur Heart J. 2008 Nov;29(21):2669-80. doi: 10.1093/eurheartj/ehn427. Epub 2008 Oct 13. Review.

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials.

Blood Pressure Lowering Treatment Trialists' Collaboration., Turnbull F, Neal B, Ninomiya T, Algert C, Arima H, Barzi F, Bulpitt C, Chalmers J, Fagard R, Gleason A, Heritier S, Li N, Perkovic V, Woodward M, MacMahon S.
BMJ. 2008 May 17;336(7653):1121-3. doi: 10.1136/bmj.39548.738368.BE. Epub 2008 May 14. Review.

Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system.

Blood Pressure Lowering Treatment Trialists' Collaboration., Turnbull F, Neal B, Pfeffer M, Kostis J, Algert C, Woodward M, Chalmers J, Zanchetti A, MacMahon S.
J Hypertens. 2007 May;25(5):951-8. Erratum in: J Hypertens. 2007 Jul;25(7):1524.

Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials.

Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J, Woodward M, MacMahon S; Blood Pressure Lowering Treatment Trialists' Collaboration.
Arch Intern Med. 2005 Jun 27;165(12):1410-9.

Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.

Turnbull F; Blood Pressure Lowering Treatment Trialists' Collaboration.
Lancet. 2003 Nov 8;362(9395):1527-35.

BPLTTC Platform.
A collaborative workspace for trialists

BPLTTC trialists will be able to work in a collaborative environment.
Some of the functionalities are: project discussions, proposals for new projects, trials search, analytics and more.

Comming soon