Blood Pressure Lowering Treatment Trialists Research Articles

Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals.

Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan+Amlodipine (ARR=8.7% compared to untreated) and 14.3% for Ramipril+Amlodipine (ARR=8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

SP-1: AGGRESSIVE BP MANAGEMENT IN OLDER ASIAN PEOPLE

With a rapidly aging population, adequate blood pressure (BP) control is critical for hypertension management and prevention of cardiovascular events. Impressive cardiovascular benefits have been observed with intensive BP control (SBP target, <120 mmHg) in the SPRINT (Systolic Blood Pressure Intervention Trial) study, even in patients 75 years of age or older. A most recent meta-analysis including 51 randomized trials with over 350,000 participants from the BPLTTC (The Blood Pressure Lowering Treatment Trialists’ Collaboration) showed that BP lowering is effective in older people for reducing major cardiovascular events. The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) study-a multicenter, randomized, controlled trial conducted in China, provided important evidence that intensive BP treatment (SBP target, 110 mmHg to < 130 mmHg) benefits older hypertensive patients (aged 60–80 years) and reduced the incidence of cardiovascular events than standard treatment (target 130 mmHg to < 150 mmHg). Because Asian people have a higher burden of hypertension and stroke than Caucasian people, intensive BP treatment has more advantages in reducing the risk of cardiovascular events including stroke in Asian hypertensive patients than in Caucasian people. Home BP monitoring is helpful to facilitate hypertension management for older patients. It should also be noted that clinical decision-making should be on a patient basis, such as fragility, diabetes, stroke, and other comorbidities, with tailored BP targets.

Blood pressure age ranges for community patient care.

British Journal of Community NursingVol. 27, No. 9 TreatmentsBlood pressure age ranges for community patient careAysha MendesAysha MendesE-mail Address: [email protected]Freelance Journalist, specialising in Healthcare and PsychologySearch for more papers by this authorAysha MendesPublished Online:7 Sep 2022https://doi.org/10.12968/bjcn.2022.27.9.422AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References National Institute for Health and Care Research. People of all ages benefit from drugs to lower blood pressure. 2022. https://evidence.nihr.ac.uk/alert/people-of-all-ages-benefit-from-drugs-to-lower-blood-pressure/ (Accessed 15 August 2022) Google ScholarThe Blood Pressure Lowering Treatment Trialists' Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021a;397(10285):1625-1636. https://doi.org/10.1016/S0140-6736(21)00590-0 Google ScholarThe Blood Pressure Lowering Treatment Trialists' Collaboration. Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis. Lancet. 2021b;398:1053-1064. https://doi.org/10.1016/S0140-6736(21)01921-8 Google Scholar FiguresReferencesRelatedDetails 2 September 2022Volume 27Issue 9ISSN (print): 1462-4753ISSN (online): 2052-2215 Metrics History Published online 7 September 2022 Published in print 2 September 2022 Information© MA Healthcare LimitedPDF download

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Blood pressure control according to type 2 diabetes status

The control of arterial hypertension is mandatory in people with and without type 2 diabetes. The Article by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), published in The Lancet Diabetes & Endocrinology.1 One-stage individual participant-level data meta-analysis of 51 major randomised controlled trials with information on type 2 diabetes status at baseline was performed. The included trials compared different antihypertensive drugs versus placebo or other classes of drugs, as well as intensive versus standard blood pressure-lowering strategies.

Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, and thiazide diuretics, was estimated using a network meta-analysis framework. This study is registered with PROSPERO, CRD42018099283. We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0-5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91-0·98]) compared with those without type 2 diabetes (0·89 [0·87-0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

IDF21-0652 Blood pressure-lowering for prevention of major cardiovascular diseases in persons with and without type 2 diabetes

Background: There is insufficient randomised evidence as to whether the effect of blood pressure (BP)-lowering treatment differs in people with type 2 diabetes versus those without this metabolic condition, particularly at a normal or high-normal BP level. Aim: To investigate the effects of BP-lowering treatment on the risk of major cardiovascular events in people with and without type 2 diabetes, and by baseline levels of systolic and diastolic BP. Method: We used the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) to conduct a one-stage individual participant data meta-analysis of major randomised trials. The primary outcome was total major cardiovascular events, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal myocardial infarction, and heart failure causing death or requiring hospitalisation. The analysis was stratified for type 2 diabetes status at baseline, and baseline categories of systolic BP (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg) and diastolic BP from <70 mm Hg to ≥110 mm Hg diastolic). Cox proportional hazard model stratified by the trial was used to estimate hazard ratio (HR). A Poisson regression model with an identity link was used to calculate the absolute risk reduction (ARR). Results: Data for 358,533 participants (58.4% men) from 51 randomised clinical trials were included in the analysis, in which 28.8% (n=103,325) of the participants had diagnosis of type 2 diabetes at baseline. Baseline mean systolic/diastolic BPs were 149/84 mm Hg in participants with type 2 diabetes (n=103,325) and 153/88 mm Hg in participants without type 2 diabetes (n=255,208). The incidence risks of primary events during the study follow-up time in participants with and without type 2 diabetes were 16.5% and 10.2%, respectively. Over 4.2 years of median follow-up, a fixed value of 5-mm Hg reduction in systolic BP was associated with a lower risk of major cardiovascular events both in participants with type 2 diabetes (HR 0.94 [95% CI 0.91 to 0.98]; ARR -0.015 [95% CI -0.020 to -0.010]) and in those without history of type 2 diabetes (HR 0.89 [95% CI 0.87 to 0.92]; ARR =-0.016 [95% CI -0.018 to -0.013]). In stratified analyses, we did not find reliable evidence for heterogeneity of treatment effects by baseline systolic or diastolic BP level in participants with or without type 2 diabetes (all P for interaction > 0.78). Discussion: The effect of BP reduction for primary and secondary prevention of major cardiovascular events was broadly comparable among people with and without type 2 diabetes, with no clinically important evidence that the level of systolic or diastolic BP at baseline is a determinant of treatment effect. Recommendations by guidelines on different BP reduction treatment in people with and without diabetes, or initiation of BP reduction therapy at a specific BP threshold, are not substantiated by these findings. This work will be presented on behalf of the Blood Pressure Lowering Treatment Trialists' Collaboration. Working group: Milad Nazarzadeh, Zeinab Bidel, Dexter Canoy, Emma Copland, Abbas Dehghan, Derrick A Bennett, George Davey Smith, Rury R. Holman, Mark Woodward, Ajay Gupta, Amanda Adler, Naveed Sattar, Richard J McManus, Koon Teo, Barry R Davis, John Chalmers, Carl J. Pepine, Kazem Rahimi.

The Blood Pressure Lowering Treatment Trialists' Collaboration: methodological clarifications of recent reports.

Epidemiological evidence has consistently shown that people with higher systolic or diastolic blood pressure are at greater risk of cardiovascular diseases. However, there has been limited randomized evidence to determine the role of blood pressure level at treatment initiation in the reduction of cardiovascular diseases risk. The extent to which other characteristics of individuals, such as prior disease history, age or sex, should be taken into account has also been controversial. Furthermore, effects on less commonly reported efficacy and safety outcomes remain underexplored. The Blood Pressure Lowering Treatment Trialists' Collaboration has collected individual-level participant data from 52 randomized clinical trials, with more than 360 000 participants, and is now the largest source of individual-level data from randomized clinical trials of blood pressure-lowering treatment. This resource provides an unprecedented opportunity to address major areas of uncertainty relating to stratified efficacy and safety of antihypertensive therapy. Recent reports have demonstrated the power of pooled analyses of the Blood Pressure Lowering Treatment Trialists' Collaboration dataset in filling long-standing gaps in our knowledge. However, there have been some misconceptions regarding the methods underpinning the recent reports, which we clarify in this article.

Do recent meta-analyses truly prove that treatment with blood pressure-lowering drugs is beneficial at any blood pressure value, no matter how low? A critical review.

Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.

Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials

ObjectiveEvidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.MethodsWe...

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis

SummaryBackgroundBlood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.MethodsWe performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists’ Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.Findings145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84–0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76–0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76–0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27–1·72]) and thiazide diuretics (RR 1·20 [1·07–1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92–1·13]).InterpretationBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.FundingBritish Heart Foundation, National Institute for Health Research, and Oxford Martin School.

Timing is everything: snoring onset and blood pressure trajectories in pregnancy.

Timing is everything: snoring onset and blood pressure trajectories in pregnancy.

Time to remove hypertension from our vocabulary?

Hypercholesterolaemia has not been part of our clinical vocabulary for several decades, so why has hypertension not gone the same way? The latest individual participant-level data meta-analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC)1 is yet another nail in the coffin for hypertension. The new study included 51 trials, with 358 707 participants (149 211 [41·6%] women and 209 496 [58·4%] men) aged 21–105 years, who had 42 947 major cardiovascular events during approximately 4 years of follow-up.

Blood pressure-lowering treatment for the prevention of cardiovascular events in patients with atrial fibrillation: An individual participant data meta-analysis.

Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.

Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis

SummaryBackgroundThe 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.MethodsWe 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.FindingsData 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.InterpretationIn 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.FundingBritish Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

EFFECTS OF BLOOD PRESSURE-LOWERING ON CANCER RISK: AN INDIVIDUAL PARTICIPANT DATA META-ANALYSIS OF 300,000 PARTICIPANTS

Objective: Evidence for the effects of pharmaceutical blood pressure (BP)-lowering on cancer risk is inconsistent and based on observational data. We therefore investigated the effect of BP-lowering on the risk of cancer in a large collaborative study. Design and method: We included randomised trials participating in the Blood Pressure-Lowering Treatment Trialists’ Collaboration. Placebo-controlled trials, drug class comparison trials and trials comparing more-vs-less intensive BP-lowering that provided individual-level participant data (IPD) on cancer events were pooled. We investigated the effects of BP reduction on cancer risk by conducting one-stage IPD meta-analyses using Cox proportional hazard models, stratified by trial and accounting for competing risks. We also investigated effects stratified by age, gender, body mass index (BMI), smoking and previous antihypertensive use at baseline. Results: This analysis included 300,098 participants (42% women) from 39 trials. At baseline, the mean age of participants was 66 (standard deviation [SD] = 9), mean BMI was 28 (SD = 5), 18% were current smokers and 75% were previously on BP-lowering medication. Over a median duration of 4 years, 16,748 participants were diagnosed with cancer, and 4347 cancer deaths were reported. The hazard ratio (HR) per 5mmHg reduction in systolic BP was 1.03 (95% confidence interval [CI] 0.99–1.07) for any cancer and 1.05 (95% CI 0.98–1.12) for cancer death. We found heterogeneity in the effects of BP-lowering across age, gender, BMI and smoking groups for any cancer and cancer death, and across groups defined by previous antihypertensive use for any cancer. However, there was no evidence that BP-lowering significantly increased the risk of developing cancer in specific patient subgroups. We found no evidence for trends in increasing or decreasing risk over time for either outcome (P for trend: any cancer = 0.98, cancer death = 0.99). Conclusions: This large-scale IPD meta-analysis found no evidence that BP-lowering had an important effect on cancer risk. Although we found that BP-lowering effects differed across several patient characteristics, there was no evidence for trend in cancer risk over time. We plan to further investigate the effects of BP-lowering on site-specific cancers (breast, colorectal, kidney, lung, prostate and skin) and present these results at the meeting.

Abstract P335: Using Cardiovascular Disease Risk Versus Blood Pressure To Guide The Initiation Of Antihypertensive Medication Among Us Adults

Introduction: The primary goal of initiating antihypertensive medication is to prevent cardiovascular disease (CVD). It has been hypothesized that using CVD risk to guide the decision to initiate antihypertensive medication may prevent more CVD events than treatment guided by blood pressure (BP) alone. Methods: We estimated the number of CVD and all-cause deaths that could be prevented among US adults through the initiation of antihypertensive medication based on high CVD risk versus high BP. CVD and all-cause mortality rates were calculated using data from 4,390 participants 40 to 79 years of age not taking antihypertensive medication from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES) mortality follow-up study. High BP was defined by systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg. High CVD risk was defined by 10-year predicted CVD risk ≥10% using the Pooled Cohort risk equations or a history of CVD. Relative risks and 95% confidence limits for CVD and all-cause mortality with antihypertensive medication of 0.75 (0.57-0.98) and 0.76 (0.63-0.91), respectively, were obtained from the Blood Pressure Lowering Treatment Trialists Collaboration. Results: Among US adults not taking antihypertensive medication, 19.4% (23.5 million) had high BP and 25.5% (30.9 million) had high CVD risk. CVD mortality rates were 5.3 and 3.9 per 1,000 person-years among US adults with high CVD risk versus high BP, respectively (Table). Using high CVD risk to guide antihypertensive medication initiation is projected to prevent 403,093 deaths from CVD over 10 years compared with 224,312 deaths from CVD projected to be prevented using a BP-guided treatment approach. More all-cause deaths are projected to be prevented by using high CVD risk (2.2 million deaths) rather than high BP (1.1 million deaths) to guide the decision to initiate antihypertensive medication. Conclusions: Using predicted CVD risk instead of BP alone to guide antihypertensive medication initiation is projected to prevent more CVD and all-cause deaths.

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)

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...

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

BackgroundClinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level.Methods and findingsWe used individual participant data from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70–0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53–0.55] for the SBP strategy). Compared with treating everyone with SBP ≥ 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%–31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%–18%) more events for the same number of persons treated. Compared with treating everyone with SBP ≥ 140 mmHg, a CVD risk strategy would require treatment of 3.8% (95% CI 12.5% fewer to 7.2% more) fewer persons to prevent the same number of events or would prevent 3.1% (95% CI 1.5%–5.0%) more events for the same number of persons treated, although the former estimate was not statistically significant. In subgroup analyses, the CVD risk strategy did not appear to be more beneficial than the SBP strategy in patients with diabetes mellitus or established CVD.ConclusionsA blood pressure-lowering treatment strategy based on predicted cardiovascular risk is more effective than one based on blood pressure levels alone across a range of thresholds. These results support using cardiovascular risk assessment to guide blood pressure treatment decision-making in moderate- to high-risk individuals, particularly for primary prevention.