Different systolic blood pressure targets for people with a history of stroke or 
transient ischaemic attack, the PAST-BP (Prevention After Stroke – Blood 
Pressure) study: randomised controlled trial  
 
 
 
 
Jonathan Mant, Professor of Primary Care Research(1) 
Richard J McManus, (2) NIHR Professor of Primary Care Research 
Andrea Roalfe, Senior Lecturer in Medical Statistics (3) 
Kate Fletcher, (3) Non-clinical Director Primary Care Clinical Research Trials Unit (PC-CRTU) 
Clare J Taylor, (3) General Practitioner and NIHR Doctoral Research Fellow 
Una Martin, (4) Professor of Clinical Pharmacology 
Satnam Virdee, (3) Research Assistant 
Sheila Greenfield, Professor of Medical Sociology (3)  
FD Richard Hobbs, Professor of Primary Care Health Sciences (2) 
 
(1) Primary Care Unit, Department of Public Health & Primary Care, Strangeways Research 
Laboratory, University of Cambridge, Wort’s Causeway, Cambridge CB1 8RN 
 
(2) Nuffield Department of Primary Care Health Sciences, NIHR School for Primary Care 
Research, University of Oxford, Oxford, OX2 6GG. 
 
(3) Primary Care Clinical Sciences, University of Birmingham, Birmingham, B15 2TT. 
 
(4) School of Clinical & Experimental Medicine, University of Birmingham, Birmingham B15 2TT. 
 
Correspondence to: 
Jonathan Mant 
 jm677@medschl.cam.ac.uk 
01223 330325 
Abstract 
Objectives:  Blood pressure lowering is effective at reducing risk of stroke recurrence in people who 
have had a cerebrovascular event, but it is uncertain how low blood pressure should be lowered in 
this population. We assessed whether using intensive blood pressure targets would lead to lower 
blood pressure in a community population of people with prevalent cerebrovascular disease.  
Design:  Open label randomised controlled trial. 
Setting:  99 General Practices in England, with participants recruited 2009-2011. 
Participants: People with a history of stroke or transient ischaemic attack whose systolic blood 
pressure was ≥ 125 mmHg. 
Interventions: Intensive systolic blood pressure target (<130mmHg or 10mmHg reduction from 
baseline if this was < 140 mmHg) or a standard target (<140mmHg).  Apart from the different target, 
patients in both arms were actively managed in the same way with regular reviews by the primary 
care team.   
Main outcome measure:  Change in systolic blood pressure between baseline and twelve months. 
Results: 529 patients, mean age 72, were enrolled, 266 to the intensive target arm and 263 to the 
standard target arm, of whom 379 were included in the primary analysis (182, 68% intensive arm; 
197, 75% standard arm). 84 patients withdrew from the study during the follow up period (52 
intensive arm; 32 standard arm).  Mean systolic blood pressure dropped by 16.1mmHg to 
127.4mmHg in the intensive target arm and by 12.8mmHg to 129.4mmmHg in the standard arm 
(difference between groups 2.9 mmHg, 95% confidence interval (0.2 to 5.7); p = 0.03). 
Conclusions:  Aiming for target below 130mmHg for systolic blood pressure in people with 
cerebrovascular disease in primary care rather than <140mmHg leads to a small additional reduction 
in blood pressure.  Active management of systolic blood pressure in this population using a 
<140mmHg target leads to a clinically important reduction in blood pressure.   
Trial Registration:  ISRCTN29062286. 
  
Introduction 
Stroke accounts for about 10% of deaths internationally, and for over 4% of direct health care costs 
in developed countries. 1 If other resources, such as lost productivity, benefits payments and 
informal care costs are taken into account, the total costs double – for example in the United 
Kingdom annual care costs are around £4.4 billion, but total costs are £9 billion per annum. 2  Over 
20% of strokes are recurrent events, 3 and if one also takes into account prior history of transient 
ischaemic attack (TIA), this figure rises to about 30%. 1  Therefore, secondary prevention has a major 
potential role to play in reducing both morbidity and costs of stroke care.  Hypertension is a key risk 
factor for stroke.  A 20 mm Hg difference in usual systolic blood pressure is associated with a 60% 
lower risk of death from stroke in someone aged 50 to 70, and a 50% lower risk in someone aged 70 
to 79. 4  
The PROGRESS trial demonstrated that treatment to lower blood pressure in people who have had a 
stroke or TIA reduces risk of further stroke. 5 However, there is debate over how to apply this 
evidence in clinical practice. 6 7 In particular, there is uncertainty over how intensively to lower blood 
pressure in people who have had a stroke or TIA. 8  A post hoc observational analysis of the PROFESS 
trial found that people with recent ischaemic stroke whose systolic blood pressure was less than 
130mmHg had a higher risk of vascular events. 9 Conversely, in PROGRESS participants whose 
baseline systolic blood pressure was 120-140mmHg who were randomised to combination therapy 
had significantly reduced stroke risk. 10 The SPS3 trial of different blood pressure targets in younger 
(mean age 63) patients with recent lacunar stroke found a non-significant 19% reduction in risk of 
stroke after one year in people treated with a systolic blood pressure target of less than 130 mmHg 
as compared to a 130-149mmHg target. 11 Recent guidelines have drawn different conclusions from 
the evidence base, with the European guidelines recommending a target systolic blood pressure of 
140mmHg (or higher) 12 and British guidelines a target of 130mmHg. 13 
In view of these controversies, the Prevention After Stroke- Blood Pressure (PAST-BP) study 
compared two different targets for blood pressure lowering after stroke or TIA in people recruited 
from a prevalent primary care population. 14  The aim was to determine whether setting a more 
intensive target in primary care would lead to a lower blood pressure, as a prelude to a trial powered 
to detect whether such a strategy would lead to a reduction in stroke recurrence.  
 
Methods 
Participants 
The methods used in PAST-BP have been reported in detail elsewhere. 14  PAST-BP was an 
individually  randomised trial in which participants were allocated either to an intensive blood 
pressure target (<130mmHg or a 10mmHg reduction if baseline pressure <140mmHg) or a standard 
target (<140 mmHg).  Patients were recruited from 106 General Practices (of whom 99 contributed 
at least one patient) in England during 2009-2011.  Patients were considered for inclusion if they 
were on the practice TIA/stroke register. They were excluded if:  their baseline systolic blood 
pressure was less than 125 mmHg; they were already on 3 or more antihypertensives; they had 
>20mmHg postural change in systolic blood pressure on standing; they were already being treated 
to a 130mmHg systolic blood pressure target; they were unable to provide informed consent; or 
there was insufficient corroborative evidence that they had had a stroke or TIA.  Potentially eligible 
participants were identified using a search of the General Practice clinical computer system. A 
general practitioner reviewed this list to exclude patients for whom a study invitation would be 
inappropriate.  The remainder were sent a letter inviting them to attend a study clinic appointment 
held at their General Practice by a research nurse, where written informed consent was obtained.   
Ethical approval was provided by the Warwickshire Research Ethics Committee (reference 
08/H1211/121).  
  
Randomisation and masking 
Randomisation was performed by the central study team at the University of Birmingham and was 
minimised on the basis of age, sex, diabetes mellitus, atrial fibrillation, baseline systolic blood 
pressure and general practice. Treatment allocation was ascertained by the research nurse either by 
telephone or online. 
Neither participants nor clinicians were blinded to treatment allocation. The primary outcome 
measure (blood pressure) was obtained using automated sphygmomanometers and measured by a 
research nurse who was not otherwise involved in the patient’s care.  
Procedures 
Patients randomised to the intensive arm were given a target systolic blood pressure < 130mmHg, or 
a target reduction of 10mmHg if their baseline blood pressure was between 125 and 140 mmHg. The 
target in the standard arm was <140 mmHg irrespective of baseline blood pressure.  Apart from the 
different blood pressure targets, the management of blood pressure was the same in both groups, 
and was carried out by a practice nurse (to monitor blood pressure) and a General Practitioner 
(responsible for modifying blood pressure treatment).  Patients whose systolic blood pressure at 
baseline was above target (everyone in the intensive arm, and those patients in the standard arm 
whose blood pressure was ≥140 mmHg) had their antihypertensive therapy reviewed by their 
General Practitioner.  A practice nurse would see all patients at three month intervals (if their blood 
pressure was below target when previously measured) or at a one month interval (if previous blood 
pressure was above target), and refer to the general practitioner if the blood pressure was above 
target.  No formal down-titration of therapy was required in the protocol if blood pressure was 
below target, but General Practitioners had discretion to change or reduce therapy in the light of 
symptoms attributable to blood pressure medication.  General Practitioners were provided with 
treatment protocols that reflected the national guidelines for blood pressure lowering in operation 
at the time of the trial. 15 In both arms of the trial, the General Practitioners had access to a 
computer based algorithm that actively suggested drugs and dosage if the participant was above 
target.  Follow up ceased if the participant had a major cardiovascular event. 
The primary outcome was change in systolic blood pressure between baseline and one year. 
Participants had blood pressure measured by a research nurse (separate from the practice nurse 
measurement described above) at baseline, six and twelve months. Blood pressure was measured 
using a British Hypertension Society validated automated electronic monitor supplied and validated 
for the study. 16 Blood pressure was measured in a standardised way, with the patient seated for five 
minutes and then six measurements taken at minute intervals. The primary outcome was the 
average of the second and third measurements.  
Secondary measures of blood pressure included diastolic blood pressure at six and twelve months, 
systolic blood pressure at six months, and proportion achieving target blood pressures at twelve 
months. For the systolic blood pressure we also calculated the means of readings 2 to 6 and 5 to 6 to 
look for any differential effects with regard to habituation to blood pressure measurement.  
Clinical events were identified through review of the general practice record at twelve months. 
These comprised: major cardiovascular events (composite of fatal and nonfatal stroke, myocardial 
infarction, fatal coronary heart disease or other cardiovascular death), emergency hospital 
admissions and deaths.  Participants were flagged for mortality at the NHS Central Register.  Side 
effects were assessed through the use of standard questionnaires. 14 
Statistical analysis 
We estimated that a sample size of 305 patients in each group would detect a 5 mmHg difference in 
systolic blood pressure between groups with 90% power at a significant level of 5% assuming a 
standard deviation of 17.5 mmHg, 10% loss to follow up, 5% mortality and 10% major vascular 
events. 5 7  For the primary analysis, mixed models were used, adjusting for baseline blood pressure, 
age group (<80 years, ≥80 years), gender, diabetes mellitus, atrial fibrillation and practice (as a 
random effect). The principal analysis was a complete case analysis. We also explored the potential 
effects of missing values by the use of three approaches: multiple imputation, group mean and by 
last available value.  Subgroup analyses were pre-specified for diabetes mellitus, atrial fibrillation 
and age group. In addition, we performed a sub-group analysis by baseline systolic blood pressure 
(<140mmHg, ≥140mmHg).  The number of consultations, treatment changes and side effects were 
compared using generalised mixed modelling, adjusting for the same variables as the primary 
outcome. For clinical events, we calculated hazard ratios and their 95% confidence interval using Cox 
proportional hazards modelling adjusting for the same covariates mentioned previously.  We 
checked the proportional hazard assumption with Schoenfeld residual plots and by including 
interaction terms in the model (for each term by time). For all clinical event analyses, patients were 
censored at the time of the first event relevant to that analysis. Thus, if a patient had more than one 
emergency hospital admission, only the first one would be counted.  Analysis was undertaken using 
SAS 9.2 and Stata 12. 
 
Patient involvement 
The study was discussed by a stroke survivor group who agreed that it was an important research 
question and that blood pressure was an important outcome for them.  Patients were involved in 
developing plans for recruitment and design of the study through representation on the Trial 
Steering Committee. No patients were asked to advise on interpretation or writing up of the results.  
We plan to disseminate the results of the research to the relevant patient community through local 
and nationally organised stroke groups. 
 
Results 
Figure 1 shows the trial profile.  529 patients from 99 general practices (range 1 – 16 per practice) 
entered the trial.  84 patients withdrew from the trial in the twelve months following randomisation 
(52, 20% in the intensive target arm and 32, 12% in the standard target arm, p =0.02).  Primary 
outcome data were available for 379 participants at one year follow up (182, 68% in the intensive 
target arm and 197, 75% in the standard target arm).  All patients were followed up for clinical 
events and deaths.  Table 1 shows baseline patient characteristics. About a quarter of participants 
were on no blood pressure lowering treatment at randomisation (76 in intensive arm; 63 in standard 
arm).  For half of participants, the index event was a TIA.  Just under 20% of participants reported at 
least moderate disability (modified Rankin score of three or more). There were no important 
differences in characteristics between participants who did and did not have blood pressure 
recorded at twelve months (see table 1).  
The intensive target arm was associated with significantly more consultations with the general 
practitioner and practice nurse for blood pressure control than the standard target arm (median 
visits 2 versus 1, p < 0.0001 and 3 versus 2, p = 0.002 respectively).   This higher consultation rate led 
to more intensifications of blood pressure treatment (458 versus 278, p < 0.0001), and more changes 
due to side effects (77 versus 30, p < 0.0001).  However, patients were also less likely to have their 
blood pressure treatment increased after review by the general practitioner when the blood 
pressure was above target in the intensive arm (109 versus 57, p = 0.005) (table 2).  The three 
factors that contributed most to this difference were symptoms attributed to blood pressure 
medication, blood pressure only just above target, and patient not wanting treatment intensified. At 
the end of the study, the number of antihypertensive drugs that patients were on in both arms had 
increased by a similar amount (mean number of antihypertensive drugs 2.1 in intensive arm and 1.9 
in standard arm, p = 0.13).   
Treatment to a more intensive target was associated with a significantly greater reduction in systolic 
blood pressure at twelve months (primary outcome) (table 3).  Systolic blood pressure was reduced 
by 16mmHg in the intensive target arm and by 13mmHg in the standard target arm.  This difference 
persisted if it was calculated using the mean of the 5th and 6th reading: -3.2 mmHg, 95%CI -5.8 to -
0.64) or the mean of the 2nd to 6th reading: -3.3mmHg, 95% CI -5.8 to -0.67) (see web appendix table 
i).  Taking account of the missing values using multiple imputation the effect size was -3.2mmHg, 
95% CI -5.7 to -0.65  (see web appendix table ii for results of other methods).   Blood pressure target 
(i.e. < 130mmHg or a 10 mm Hg reduction for those with a baseline systolic blood pressure < 
140mmHg) at one year was achieved in 93 (51.1%) patients in the intensive arm.  Proportions 
achieving a systolic blood pressure < 140 mmHg were similar in the two arms (150/182, 82.4% versus 
161/197, 81.7%, p = 0.59), as were those achieving a systolic blood pressure <130mmHg (103/182, 
56.6% versus 107/197, 54.3%, p = 0.36). There was no evidence of a significant difference in 
effectiveness of using an intensive blood pressure target in any patient sub-group (figure 2).  
There was one major cardiovascular event in the intensive target arm (a non-fatal myocardial 
infarction), and five in the standard care arm (3 strokes;  1 non-fatal myocardial infarction and 1 
cardiovascular death) (HR 0.19, 95% CI 0.02 to 1.87, p = 0.16). There were two deaths in the 
intensive target arm and one in the standard target arm. Risk of emergency admission was 12.8% 
per annum in the intensive target arm and 7.8% per annum in the standard target arm (HR 1.56, 
95%CI 0.84 to 2.93, p = 0.16).  Two admissions in each arm were related to falls. Apart from TIA 
(responsible for five admissions in the standard target arm and three admissions in the intensive 
target arm) and stroke, no single diagnosis accounted for more than two admissions.  Table 4 shows 
the commonest symptoms at twelve months by treatment allocation. There were no significant 
differences between the two groups.  
 
Discussion 
Statement of principal findings 
We found that aiming for a target systolic blood pressure of <130 mmHg or 10mmHg reduction from 
baseline if this was < 140 mmHg in a primary care population with prevalent cerebrovascular disease 
led to a lower systolic blood pressure than if a <140 mmHg target was aimed for, but the difference 
was small – about 3mmHg and was associated with increased workload – an extra consultation each 
for GPs and nurses per year. The intensive target arm was not associated with more side effects as 
measured at follow up, but there were more changes to treatment because of side effects during 
the trial.  More people withdrew consent for the trial from the intensive target arm, and this might 
have reflected unwillingness to persevere with the increased medication regime.  Perhaps the most 
important finding was the greater than 10mmHg reductions in mean systolic blood pressure in both 
arms of the study,   so that over 80% of participants in each arm had achieved a blood pressure of < 
140mmHg by the end of the trial, as compared to less than 50% at baseline.   
 
Strengths and weaknesses of the study 
Blood pressure at twelve months was not available for 28% of patients randomised. This reflected a 
high number of patient withdrawals from the study, with some differential loss to follow up in the 
intensive target arm.  However, if missing values were imputed using multiple imputation – the most 
robust method -the difference in achieved blood pressure between arms at one year was very 
similar to that observed.  Although we did not achieve our sample size, in the event our trial was 
adequately powered, since the observed standard deviation in blood pressure was less than we had 
anticipated in our sample size calculation. This is reflected in the statistical significance of the small 
difference in observed blood pressure between arms.  Nevertheless, the upper limit of the 
confidence interval around the difference between arms at one year was 5.68mmHg, which would 
be regarded as a clinically important effect.  Only 4% of patients on general practice stroke/TIA 
registers participated in the trial. Participants had a low prevalence of disability for a prevalent 
cerebrovascular disease population, were younger than typical patients in primary care with a 
history of cerebrovascular disease and over-represented people with a history of TIA only. 7  It is 
likely therefore that the more intensive target would have been even harder to achieve if the trial 
population was more representative of people with prevalent cerebrovascular disease.  The trial 
represents a post-stroke primary care population managed by generalists rather than a selective 
hospital/ out-patient population managed by specialists. The outcome measure was unblinded, but 
obtained using an automated sphygmomanometer by a nurse not directly involved in the 
participant’s care, so systematic recording bias is unlikely.  
The standard target arm in PAST-BP was actively managed, with support of a computer based 
algorithm that suggested medication changes rather than simply receiving ‘usual care’.  If we had 
used a more passive management strategy in the comparison group, we may have achieved a 
greater separation in systolic blood pressure between arms.  In another blood pressure lowering 
study of patients with increased cardiovascular risk undertaken by our group in the same timeframe, 
the standard care control arm dropped by 6mmHg from a similar baseline compared to 13mmHg in 
the current study. 17  We used an active control as we wanted to ascertain the impact of setting 
different blood pressure targets, and to avoid confounding that would be introduced by having 
different management strategies in the two arms. The target in the intensive arm was more 
complicated than that in the standard care arm, but we minimised the impact of this on protocol 
adherence by ensuring that the primary care staff managed all trial participants in the same way, 
with prompts to review treatment if it was above the individualised target.  
Comparison with other studies and interpretation 
The change in mean blood pressure that we observed in the intensive target arm was very similar to 
that observed in the <130mmHg target arm of the SPS3 trial, with both PAST-BP and SPS3 achieving 
a mean systolic blood pressure in the intensive arm of 127 mmHg after one year. 11  However, the 
comparison arms had different achieved blood pressures (PAST-BP 129 mmHg versus SPS3 138 
mmHg).  This reflects the more conservative target in the higher target arm of SPS3 (130-149mmHg 
as opposed to <140mmHg), and that antihypertensive therapy was reduced if blood pressure fell 
below target.   
Most of the observed reduction in blood pressure is likely to have been mediated by increased use 
of antihypertensive drugs, which on average went up from 1 to 2 drugs per person over the year of 
the study in both arms of the trial. Alternative explanations are that there was habituation to blood 
pressure measurement leading to reduced white coat effect, or that there was regression dilution 
bias. However, in a blood pressure monitoring trial in a similar post-stroke population with similar 
mean baseline systolic blood pressure, no fall in blood pressure was observed in the control group 
over a twelve month period, 18  and in the SPS3 trial (also with similar mean baseline systolic blood 
pressure to PAST-BP) there was a fall of just 4 mmHg in the 140 mmHg target arm over the study 
period. 11  This suggests that the fall of 13 mmHg observed in the standard target arm of PAST-BP is 
unlikely to be primarily due to effects of regression dilution or habituation to measurement.  Given 
that we had a relatively low systolic blood pressure inclusion criterion of ≥ 125 mmHg, important 
regression dilution bias would not be anticipated in this study.  
Only 51% of patients in the intensive target arm of PAST-BP achieved their target blood pressure.  
Both patient wishes and general practitioner decision making led to treatment not being intensified 
when blood pressure was above target (table 2).  Greater reluctance to lower blood pressure when 
near target, higher attribution of symptoms to blood pressure medication (table 2) despite an 
absence of objective evidence of increased symptoms (table 4) in the intensive target arm and 
greater reluctance of patients to increase treatment hint at the difficulties faced in achieving lower 
blood pressure targets in clinical practice. 19  This impression of practical difficulty is reinforced by 
the  significantly higher proportion of participants that withdrew from the trial in the intensive arm. 
Although reported side effects and symptoms were similar in the two arms, and serious adverse 
events were infrequent (two admissions for falls in each arm), significantly more changes to 
treatment needed to be made because of side effects in the intensive target arm.   
 
Implications 
Recent evidence from SPRINT and a systematic review highlight the benefits of intensive blood 
pressure lowering. 20 21  In some blood pressure target trials such as SPRINT and SPS3, the trial design 
maximised the achieved difference in blood pressure between the two arms, with the less intensive 
arm having a target range rather than simply a < 140mmHg systolic target, and with treatment being 
reduced if blood pressure fell below the target range. This is an appropriate design for an 
explanatory trial designed to test the question does lowering blood pressure reduce risk of 
cardiovascular events? In our pragmatic trial which sought to test the effect of different blood 
pressure targets as they would be used in clinical practice, the protocol did not stipulate a reduction 
in blood pressure therapy if the blood pressure was below target and the control arm was actively 
managed to achieve a target blood pressure < 140mmHg.  As a result of this, and of reluctance on 
the part of both clinicians and patients to instigate all increases in blood pressure medication in the 
intensive group, the achieved difference in blood pressure between the two arms was small.  
Nevertheless, we found that active management was associated with clinically important reductions 
in blood pressure in both arms – the 13mmHg reduction achieved in the < 140mmHg arm equates to 
over 40% and 20% reduction in risk of stroke and coronary heart disease respectively. 22 Indeed, the 
reduction in blood pressure in our less intensive arm was similar to that achieved in the active arms 
of other blood pressure lowering trials and more than in their control groups. 11 17 The additional 
resources required to achieve the additional 3mmHg lower blood pressure in the intensive target 
arm might be better spent in increasing the proportion of people with stroke in primary care who 
have a systolic blood pressure < 140mmHg. Given this conclusion we did not feel that a pragmatic 
trial powered to detect a difference in cardiovascular end-points using an intensive target in primary 
care was warranted. Furthermore, the ongoing ESH-CHL SHOT trial will provide important data on 
whether intensive blood pressure lowering reduces cardiovascular events in people with stroke (who 
were excluded from the SPRINT trial). 23 The explanatory trial design is likely to lead to clear 
differences in achieved blood pressure in the treatment arms and confirm whether or not intensive 
blood pressure lowering reduces cardiovascular end-points in the post-stroke population.   
 
 
  
Panel: What this paper adds 
What is already know on this subject 
 Lowering blood pressure after stroke is associated with lower risk of stroke recurrence, but 
there is uncertainty over what the target blood pressure should be 
 One trial in people with recent lacunar stroke found that a systolic blood pressure target of < 
130mmHg was associated with a non-significant reduction in stroke compared to a target of 
130-149mmHg 
 No trials have been carried out in primary care settings of different blood pressure targets 
after stroke 
 
What this study adds 
 Patients set a target of < 130mmHg or a 10mmHg reduction if initial blood pressure < 
140mmHg achieved lower systolic blood pressures than those set a target of < 140mmHg, 
but the difference was small (3mmHg) in the context of the reduction in blood pressure 
observed in both arms (13mmHg and 16mmHg). 
 Active management of blood pressure after stroke/TIA  is more important than the target 
that is set. 
 
 
 
Details of Contributors 
JM, RMcM, SG & FDRH had the original idea and gained the funding.  KF, JM, RMcM, CT, UM, SV, SG 
& FDRH contributed to the protocol.  AR conducted the primary data analysis. KF & SV were 
responsible for the data collection. JM wrote the first draft of the paper. All authors subsequently 
refined the manuscript and approved the final version. JM is the study guarantor. JM affirms that the 
manuscript is an honest, accurate, and transparent account of the study being reported; and that no 
important aspects of the study have been omitted. There are no discrepancies from our original 
plans for this study. 
 
All authors have full access to all of the data (including statistical reports and tables) in the study and 
can take responsibility for the integrity of the data and the accuracy of the data analysis. 
 
Funding 
This report is independent research funded by the National Institute for Health Research (Stroke 
Prevention in Primary Care, Programme Grant for Applied Research, RP-PG-0606-1153), and by an 
NIHR Professorship (Prof McManus). FDRH is part funded as Director of the National Institute for 
Health Research (NIHR) School for Primary Care Research (SPCR), Theme Leader of the NIHR Oxford 
Biomedical Research Centre (BRC), and Director of the NIHR Collaboration for Leadership in Applied 
Health Research and Care (CLAHRC) Oxford. The views expressed in this publication are those of the 
author(s) and not necessarily those of the NHS. The study sponsor was the University of Birmingham. 
The study funder and sponsor had no role in the study design, collection, analysis or interpretation 
of data, in the writing of the report, or in the decision to submit to publication. The researchers are 
independent of the funders.  
 
Data sharing 
No additional data available. 
A CC BY licence is required. 
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All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf 
and declare: Professor Mant reports grants from Ferrer and NIHR; Professor McManus reports 
grants from Ferrer,  during the conduct of the study; grants and personal fees from Omron, grants 
from Lloyds Pharmacy, personal fees and other from Japanese Society of Hypertension, personal 
fees and other from American Society of Nephrology,  outside the submitted work; Mrs. Roalfe 
reports grants from University of Birmingham,  during the conduct of the study; Dr. Hobbs reports 
grants from NIHR, non-financial support from Omron & Microlife,  during the conduct of the study; 
no other support from any organisation for the submitted work; no other financial relationships with 
organisations that might have interest in the submitted work; no other relationships or activities 
that could appear to have influenced the submitted work.   
 
  
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32:1888-97. 
 
 LEGEND FOR FIGURES  
(Figures provided in separate file) 
Figure 1: Trial profile 
‡ Reasons given: patient was housebound or in a nursing home (957, 33%); would be unable to 
provide consent (338, 12%); co-morbidity (216, 7%); blood pressure too low (199, 7%); at risk of 
falling (164, 6%); insufficient evidence of stroke/TIA (98, 3%); already being treated to 130 mmHg 
target (71, 2%); other patient factors (69, 2%); patient choice (54, 2%); terminally ill (48, 2%); 
deceased or left practice (41, 1%); participating in another trial (9). In 618 (21%) cases, no reason 
was given. 
†blood pressure < 125mmHg 447; lack of corroborative evidence of stroke/TIA 60; on 3 or more 
antihypertensives 51; orthostatic hypotension 22; already being treated to lower BP target 4; unable 
to provide informed consent 2. 
SBP: Systolic Blood Pressure 
Figure 2 Effect of intensive versus standard target on systolic BP at twelve months for different 
patient sub-groups  
Adjusted for baseline blood pressure, age group (<80, ≥80), gender, diabetes mellitus, atrial 
fibrillation and general practice (random effect) 
 
 
  
 All participants Participants with systolic blood pressure 
recorded at 12 months 
 Intensive target Standard target Intensive target Standard target 
 n=266 n=263 n=182 n=197 
Age (years)                     71.9 (9.1) 71.7 (9.4) 72.6 (8.3) 71.9 (9.5) 
Men 157 (59.0) 156 (59.3) 104 (57.2) 125 (63.5) 
White ethnicity 260 (97.7) 259 (98.5) 180 (98.8) 194 (98.5) 
Current smoker 25 (9.4) 33 (12.6) 15 (8.3) 27 (13.9) 
Systolic blood pressure 
  <140mmHg 
  >=140mmHg                                         
142.9 (14.0) 
128 (48.1) 
138 (51.9) 
142.2 (13.4)  
129 (49.1) 
134 (50.9) 
143.5 (13.5) 
79 (43.4) 
103 (56.6) 
142.2 (12.9)  
98 (49.8) 
99 (50.3) 
Diastolic blood pressure         79.9 (10.0)      80.4 (9.8)           78.8 (9.3)      80.7 (10.1)      
Diabetes mellitus 26 (9.8) 25 (9.5) 19 (10.4) 21 (10.7) 
Atrial Fibrillation 28 (10.5) 27 (10.3) 21 (11.5) 22 (11.2) 
Coronary heart disease 41 (15.4) 46 (17.5) 28 (15.4) 35 (17.8) 
Chronic kidney disease 26 (9.8) 30 (11.4) 19 (10.4) 23 (11.7) 
Heart failure 2 (0.8) 7 (2.7) 1 (0.6) 6 (3.1) 
Peripheral vascular disease 11 (4.1) 11 (4.2) 7 (3.9) 6 (3.1) 
Stroke 130 (48.9) 122 (46.4) 85 (46.7) 95 (48.2) 
TIA only 135 (50.8) 141 (53.6) 97 (53.3) 102 (51.8) 
Number of antihypertensive drugs 
Number of other drugs 
Total number of drugs  
1.0 (0.8) 
4.5 (2.5) 
5.6 (2.8) 
1.1 (0.8) 
4.6 (2.6) 
5.7 (2.7) 
1.1 (0.8) 
4.5 (2.5) 
5.6 (2.7) 
1.1 (0.8) 
4.6 (2.6) 
5.7 (2.7) 
Modified Rankin scale† 
0 or 1 
 
135 (50.8) 
 
125 (47.5) 
 
98 (53.8) 
 
84 (42.6) 
2 65 (24.4) 69 (26.2) 42 (23.1) 57 (28.9) 
3 or 4 47 (17.7) 51 (19.4)  29 (15.9) 42 (21.3) 
Table 1: Baseline characteristics 
Data are mean (SD) or number (%); †Data missing for 19 patients in intensive arm and 18 in standard arm (all 
participants) and for 13 patients in intensive arm and 14 in standard arm (participants with 12 month systolic 
blood pressure). 
  Intensive target  
(n=109) 
Standard target  
(n=57) 
 
Other blood pressure readings (e.g. home readings) taken into account 
 
17 20 
Patient did not want treatment intensified 
 
22 13 
Decision taken to re-measure blood pressure at future time 
 
19 12 
Symptoms attributed to blood pressure medication 
 
24 5 
Blood pressure only just above target 
 
14 2 
Patient had not been taking pills 
 
9 5 
Blood pressure reading attributed to patient anxiety 
 
3 8 
Changes to drug therapy already made 4 2 
 
Postural hypotension 3 2 
 
Awaiting specialist advice/ test results 
 
5 - 
Intercurrent illness 
 
3 - 
Patient too old for further increases in therapy 
 
1 2 
Change in lifestyle advocated rather than change in medication 
 
- 1 
 
Table 2: Reasons given by general practitioner for not increasing blood pressure medication after 
patient referred by practice nurse with blood pressure above target 
 
A reason was given for 164 of 166 non-intensification decisions. Numbers add up to more than 164 as in some 
cases two reasons were given. 
  Mean blood pressure (mm Hg) Mean difference from baseline 
(mm Hg) 
Effect size (mm Hg, 95% CI)† 
 Baseline 6 months 
 
12 months 6 months 12 months 6 months 12 months 
 Systolic blood pressure 
 
     
Intensive target‡ 
 
143.5 (13.5) 125.7 (14.5) 127.4 (14.8) -17.3 (16.7) -16.1 (15.0) -4.12 (-6.84 to -1.40) -2.94 (-5.68 to -0.21) 
Standard target* 
 
142.2 (12.9) 129.3 (14.6) 129.4 (14.8) -12.7 (16.7) -12.8 (17.2) .. .. 
 Diastolic blood pressure 
 
     
Intensive target‡ 
 
78.8 (9.3) 73.1 (10.3) 72.0 (9.0) -6.5 (10.7) -6.8 (9.1) -1.14 (-2.86 to 0.58) -1.63 (-3.10 to -0.15) 
Standard target* 
 
80.7 (10.1) 74.6 (9.8) 74.4 (8.9) -6.1 (9.7) -6.3 (9.4) .. .. 
 
Table 3: Systolic and diastolic blood pressure in intensive target and standard target groups 
Data are mean (standard deviation) 
†Adjusted for baseline blood pressure, age group (<80, ≥80), gender, diabetes mellitus, atrial fibrillation and general practice (random effect) 
‡Blood pressure data for 193 intensive target patients at six months and 182 at twelve months 
*Blood pressure data for 198 standard target patients at six months and 197 at twelve months 
 
 
  
  
 
 Intensive target 
arm 
Standard target arm Effect size 
Odds ratio (95% CI) 
P value 
     
Pain 93/163 (57%) 89/173 (51%) 1.17 (0.75 to 1.84) 0.48 
Breathlessness 53/148 (36%) 49/158 (31%) 1.17 (0.72 to 1.92) 0.53 
Fatigue 75/149 (50%) 88/163 (54%) 0.81 (0.51 to 1.28) 0.36 
Stiff joints 93/162 (57%) 99/176 (56%) 0.94 (0.59 to 1.49) 0.80 
Sore eyes 35/148 (24%) 24/158 (15%) 1.68 (0.93 to 3.04) 0.08 
Wheeziness 32/163 (20%) 28/175 (16%) 1.24 (0.70 to 2.21) 0.46 
Headaches 27/151 (18%) 36/165 (22%) 0.69 (0.38 to 1.24) 0.22 
Sleep difficulties 56/150 (37%) 66/163 (40%) 0.81 (0.51 to 1.31) 0.39 
Dizziness 45/164 (27%) 39/173 (23%) 1.24 (0.74 to 2.08) 0.42 
Loss of strength 44/148 (30%) 51/162 (31%) 0.85 (0.51 to 1.40) 0.52 
Loss of libido 47/160 (29%) 50/171 (29%) 1.06 (0.65 to 1.72) 0.83 
Impotence 29/129 (22%) 31/145 (21%) 1.22 (0.65 to 2.30) 0.54 
 Pins and needles 54/163 (33%) 44/176 (25%) 1.48 (0.91 to 2.41) 0.11 
Cough 40/144 (28%) 49/160 (31%) 0.86 (0.51 to 1.44) 0.57 
Swelling of 
legs/ankles 
51/162 (31%) 49/177 (28%) 1.10 (0.67 to 1.81) 0.70 
Dry mouth 34/147 (23%) 36/161 (22%) 0.98 (0.57 to 1.70) 0.95 
 
Table 4: Most frequent symptoms at 12 months 
Adjusted for baseline systolic blood pressure, age group (<80, ≥80), gender, diabetes mellitus, atrial fibrillation 
and general practice (random effect)    
 
 
 
 
 
Figure 2 Effect of intensive versus standard target on systolic BP at twelve months for different 
patient sub-groups  
Adjusted for baseline blood pressure, age group (<80, ≥80), gender, diabetes mellitus, atrial fibrillation and 
general practice (random effect) 
 
 Figure 1