Article Text
Abstract
Introduction Previous 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 analysis RCTs 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 dissemination Ethics 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.
- blood pressure
- meta-analyses
- efficacy and safety of bp lowering treatment
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Footnotes
Contributors KR: wrote the first draft of the manuscript; KR and DC: sought access to the data; DC, MN and KR: conducted the systematic review; KR, DC, MN, GSK, MW, KT, BRD, JC and CJP: contributed in the conception and design of the study, provided critical input into the subsequent revisions of the manuscript and gave approval to the final version to be published; KR and DC: are guarantors of this protocol.
Funding BPLTTC is supported by the Oxford Martin School and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).
Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health; Funders have no involvement in the conduct of the review or in the development of the protocol.
Competing interests George Health Enterprises, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin, and blood pressure-lowering drugs. George Health Enterprises has submitted patents for low-dose blood pressure combinations on which one of the collaborators (A Rodgers) is listed as one of the inventors, but does not have a financial interest in these planned products.
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators The Blood Pressure Lowering Treatment Trialists’ Collaboration: Steering Committee: Kazem Rahimi (Chair) (The George Institute for Global Health, University of Oxford, Oxford, United Kingdom), Koon Teo (Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada) Barry R Davis (The University of Texas School of Public Health, Houston, Texas, USA), John Chalmers (The George Institute for Global Health, University of New South Wales, Sydney, Australia), Carl J. Pepine (Department of Medicine, University of Florida, Gainesville, Florida, USA). Collaborating Trialists: L Agodoa (AASK [African-American Study of Kidney Disease and Hypertension]), A Algra (Dutch TIA Study [Dutch Transient Ischemic Attack Study]), F W Asselbergs (PREVEND-IT [Prevention of Renal and Vascular End- stage Disease Intervention Trial]), N Beckett (HYVET [Hypertension in the Very Elderly Trial]), E Berge (VALUE trial [Valsartan Antihypertensive Long-term Use Evaluation trial]), H Black (CONVINCE [Controlled Onset Verapamil Investigation of Cardiovascular End Points]), F.P.J. Brouwers (PREVEND-IT), M Brown (INSIGHT [International Nifedipine GITS Study: Intervention as a Goal in Hypertension]), C J Bulpitt (HYVET), B Byington (PREVENT [Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial]), J Chalmers (ADVANCE [Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation]), J Cutler (ALLHAT [Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial]), B Davis (ALLHAT), R B Devereaux (LIFE [Losartan Intervention For Endpoint reduction in hypertension]), D Dwyer (IDNT [Irbesartan Diabetic Nephropathy Trial]), R Estacio (ABCD [Appropriate Blood Pressure Control in Diabetes]), R Fagard (SYST-EUR [SYSTolic Hypertension in EURope]), K Fox (EUROPA [European trial on Reduction Of cardiac events with Perindopril among patients with stable coronary Artery disease]), T Fukui (CASE-J [Candesartan Antihypertensive Survival Evaluation in Japan]), A J Gupta (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial]), R R Holman (UKPDS [UK Prospective Diabetes Study]), Y Imai (HOMED-BP [Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure]), M Ishii (JMIC-B [Japan Multicenter Investigation for Cardiovascular Diseases-B]), S Julius (VALUE), Y Kanno (E-COST [Efficacy of Candesartan on Outcome in Saitama Trial]), S E Kjeldsen (VALUE, LIFE), J Kostis (SHEP [Systolic Hypertension in the Elderly Program]) K Kuramoto (NICS-EH [National Intervention Cooperative Study in Elderly Hypertensives]), J Lanke (STOP2 [Swedish Trial in Old Patients with Hypertension-2], NORDIL [Nordic Diltiazem]), E Lewis (IDNT), J Lewis (IDNT) M Lievre (DIABHYCAR [Non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril study]), L H Lindholm (CAPPP [Captopril Prevention Project], STOP2, NORDIL), S Lueders (MOSES [The Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention]), S MacMahon (ADVANCE), M Matsuzaki (COPE [The Combination Therapy of Hypertension to Prevent Cardiovascular Events]), M H Mehlum (VALUE), S Nissen (CAMELOT [Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis]), H Ogawa (HIJ-CREATE [Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Heart Disease]), T Othisgihara (CASE-J), T Ohkubo (HOMED-BP), C Palmer (INSIGHT), A Patel (ADVANCE), C Pepine (INVEST [International Verapamil SR-Trandolapril Study]), M Pfeffer (PEACE [Prevention of Events With Angiotensin- Converting Enzyme Inhibition]), N R Poulter (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial]), H Rakugi (VALISH [Valsartan in Elderly Isolated Systolic Hypertension Study], CASE-J), G Remuzzi (BENEDICT [BErgamo NEphrologic DIabetes Complications Trial]), P Ruggenenti (BENEDICT), T Saruta (CASE-J), J Schrader (MOSES), R Schrier (ABCD), P Sever (ASCOT), P Sleight (CONVINCE, HOPE [Heart Outcomes Prevention Evaluation], TRANSCEND [Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease], ONTARGET [Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial]), J A Staessen (SYST-EUR [Systolic Hypertension in Europe]), H Suzuki (ECOST), L Thijs (Syst-Eur), K Ueshima (VALISH, CASE-J), S Umemoto (COPE), W H van Gilst (PREVEND-IT), P Verdecchia (Cardio-Sis [CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica]), K Wachtell (LIFE), L Wing (ANBP2 [The Second Australian National Blood Pressure Study]), Y Yui (JMIC-B), S Yusuf (HOPE, ONTARGET, TRANSCEND), A Zanchetti (deceased) (VHAS [Verapamil in Hypertension and Atherosclerosis Study], ELSA [European Lacidipine Study on Atherosclerosis]). Other members: C Baigent, R Collins, D de Zeeuw B Neal, V Perkovic, M Rahman, W J Remme, A Rodgers, J Sundström, F Turnbull.