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

Abstract

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. 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.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. Haz...

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

“…A one-stage individual participant data meta-analysis framework was used for statistical analysis. 21 We used stratified Cox proportional hazard models, with fixed treatment effects and participants as the unit of analysis. 22 We standardised the effect sizes for a 5 mm Hg reduction in systolic blood pressure between randomised groups as a convenient round value close to the weighted mean of systolic blood pressure reduction across all trials.…”

“… 22 We standardised the effect sizes for a 5 mm Hg reduction in systolic blood pressure between randomised groups as a convenient round value close to the weighted mean of systolic blood pressure reduction across all trials. 19 , 21 Standardisation of effect size is useful when the aim is to assess the effects of blood pressure reduction through pooling of the data from different trials with differing amounts of blood pressure reduction. 21 Patients entered the analysis at the date of randomisation and were followed up until the earliest occurrence of type 2 diabetes, death, study exit, or end of the trial.…”

“… 19 , 21 Standardisation of effect size is useful when the aim is to assess the effects of blood pressure reduction through pooling of the data from different trials with differing amounts of blood pressure reduction. 21 Patients entered the analysis at the date of randomisation and were followed up until the earliest occurrence of type 2 diabetes, death, study exit, or end of the trial. Kaplan-Meier survival curves were used to compare the probability of survival during the follow-up time.…”

“…The risk of bias for each trial was assessed by the revised Cochrane risk-of-bias tool and has been reported in a previous study. 21 …”

Randomized controlled trial of stress reduction with meditation and health education in black men and women with high normal and normal blood pressure

“…The Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTT) reported a meta-analysis of 48 trials of pharmacologic interventions with 350,000 participants with a wide range of baseline blood pressures [ 50 , 51 ][52]. In patients with systolic BP in the high normal range and with no prior CVD, as was the case for participants in this trial, a standardized reduction of 5 mm Hg SBP was associated a 10% reduction in major adverse cardiovascular events with [ 50 , 52 , 53 ]. For these reasons, the International, European and American guidelines all recommend lifestyle modification for individuals with high normal BP (or stage I equivalent), especially for those without concomitant CVD as was the case for participants in this trial.…”