TY - JOUR
T1 - Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure
T2 - an individual participant-level data meta-analysis
AU - Algra, Ale
AU - Asselbergs, Folkert
N1 - Funding Information:
This research was funded by the BHF (PG/18/65/33872 and FS/19/36/34346), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, and the Oxford Martin School. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health and Social Care. This manuscript was prepared using ACCORD, ALLHAT, PEACE, and SHEP studies' research materials obtained from the US National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Centre and does not necessarily reflect the opinions or views of the ACCORD, ALLHAT, PEACE, and SHEP investigators, or the NHLBI. The AASK study was done by AASK investigators and supported by the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the AASK study reported here were supplied by the NIDDK central repositories. This manuscript was not prepared in collaboration with the investigators of the AASK study and does not necessarily reflect the opinions or views of AASK, the NIDDK central repositories, or the NIDDK. We acknowledge the original depositors of the Australian National Blood Pressure Study data and the Australian Data Archive, and declare that those who carried out the original analysis and collection of the data bear no responsibility for the further analysis or interpretation of the data.
Funding Information:
This research was funded by the BHF (PG/18/65/33872 and FS/19/36/34346), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, and the Oxford Martin School. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health and Social Care. This manuscript was prepared using ACCORD, ALLHAT, PEACE, and SHEP studies' research materials obtained from the US National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Centre and does not necessarily reflect the opinions or views of the ACCORD, ALLHAT, PEACE, and SHEP investigators, or the NHLBI. The AASK study was done by AASK investigators and supported by the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the AASK study reported here were supplied by the NIDDK central repositories. This manuscript was not prepared in collaboration with the investigators of the AASK study and does not necessarily reflect the opinions or views of AASK, the NIDDK central repositories, or the NIDDK. We acknowledge the original depositors of the Australian National Blood Pressure Study data and the Australian Data Archive, and declare that those who carried out the original analysis and collection of the data bear no responsibility for the further analysis or interpretation of the data.
Funding Information:
MW reports personal fees from Amgen, Kyowa Kirin, and Freeline. MN and DC report grants from the British Heart Foundation (BHF). KR reports grants from BHF, the UK Research and Innovation Global Challenges Research Fund, Oxford Martin School (University of Oxford, Oxford, UK), and National Institute for Health Research Oxford Biomedical Research Centre (University of Oxford); and personal fees from British Medical Journal Heart and Public Library of Science Medicine. JC reports grants from the National Health and Medical Research Council of Australia. EC, ZB, RR, KKT, CJP, A-CP-G, and BRD declare no competing interests.
Publisher Copyright:
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Background: The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods: We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat. Findings: Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19·8%) of participants with previous cardiovascular disease and 14 928 (8·0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4·15 years' follow-up (Q1–Q3 2·97–4·96), 42 324 participants (12·3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31·9 (95% CI 31·3–32·5) in the comparator group and 25·9 (25·4–26·4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0–40·5) and 36·0 (95% CI 35·3–36·7), in the comparator and intervention groups, respectively. Hazard ratios (HR) associated with a reduction of systolic blood pressure by 5 mm Hg for a major cardiovascular event were 0·91, 95% CI 0·89–0·94 for partipants without previous cardiovascular disease and 0·89, 0·86–0·92, for those with previous cardiovascular disease. In stratified analyses, there was no reliable evidence of heterogeneity of treatment effects on major cardiovascular events by baseline cardiovascular disease status or systolic blood pressure categories. Interpretation: In this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high–normal blood pressure values. These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment. Physicians communicating the indication for blood pressure lowering treatment to their patients should emphasise its importance on reducing cardiovascular risk rather than focusing on blood pressure reduction itself. Funding: British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.
AB - Background: The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods: We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat. Findings: Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19·8%) of participants with previous cardiovascular disease and 14 928 (8·0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4·15 years' follow-up (Q1–Q3 2·97–4·96), 42 324 participants (12·3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31·9 (95% CI 31·3–32·5) in the comparator group and 25·9 (25·4–26·4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0–40·5) and 36·0 (95% CI 35·3–36·7), in the comparator and intervention groups, respectively. Hazard ratios (HR) associated with a reduction of systolic blood pressure by 5 mm Hg for a major cardiovascular event were 0·91, 95% CI 0·89–0·94 for partipants without previous cardiovascular disease and 0·89, 0·86–0·92, for those with previous cardiovascular disease. In stratified analyses, there was no reliable evidence of heterogeneity of treatment effects on major cardiovascular events by baseline cardiovascular disease status or systolic blood pressure categories. Interpretation: In this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high–normal blood pressure values. These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment. Physicians communicating the indication for blood pressure lowering treatment to their patients should emphasise its importance on reducing cardiovascular risk rather than focusing on blood pressure reduction itself. Funding: British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.
UR - http://www.scopus.com/inward/record.url?scp=85104906763&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(21)00590-0
DO - 10.1016/S0140-6736(21)00590-0
M3 - Article
C2 - 33933205
SN - 0140-6736
VL - 397
SP - 1625
EP - 1636
JO - Lancet (London, England)
JF - Lancet (London, England)
IS - 10285
ER -