Even in those with normal or only mildly elevated blood pressure (BP), anti-hypertensive medication lowering of BP protects against future cardiovascular (CV) events, found a large meta-analysis in The Lancet. 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 (CVD), and even at normal or high–normal blood pressure values.
"The take-home message is that pharmacological blood pressure lowering should be considered as a tool for cardiovascular risk management even when blood pressure is normal or mildly elevated, for primary and secondary prevention of CVD," said lead investigator Dr Kazem Rahimi, University of Oxford.
"The advice to patients with normal blood pressure and high CVD risk is that they are likely to benefit from taking one or several antihypertensive medications to reduce their risk of suffering a major cardiovascular event in the future," Rahimi added.
For this analysis, Rahimi and colleagues looked at individual participant-level data from 48 randomized antihypertensive treatment trials. Participants were divided into seven subgroups based on systolic blood pressure baseline (less than 120, 120-129, 130-139, 140-149, 150-159, 160-169, 170 and above mm Hg).
The analysis included 344,716 patients with ≥1000 patient-years per allocated group.
Over an average 4 years of follow-up, a 5 mm Hg reduction in systolic blood pressure lowered the relative risk for major CV events by about 10%.
The risks for stroke, heart failure, ischaemic heart disease, and death from CVD were reduced by 13%, 13%, 8%, and 5%, respectively.
The relative risk reductions were proportional to the intensity of blood pressure-lowering. Neither the presence of CVD nor the level of blood pressure at study entry modified the effect of treatment.
"This study calls for a change in clinical practice that predominantly confines antihypertensive treatment to people with higher than average blood pressure values," Rahimi and colleagues write.
"On the basis of this study, the decision to prescribe blood pressure medication should not be based simply on a previous diagnosis of cardiovascular disease or an individual's current blood pressure. Rather, blood pressure medication should be viewed as an effective tool for preventing cardiovascular disease when an individual's cardiovascular risk is elevated," they say.
In a linked editorial, Dr Thomas Kahan, Karolinska Institute, Stockholm, Sweden, writes that "the study by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) represents the largest meta-analysis so far of individual participant-level data for the effects of antihypertensive treatment stratified by initial blood pressure and prevalent cardiovascular disease. The results showed that the benefit of antihypertensive drug treatment is proportional to the intensity of blood pressure reduction, and that the magnitude of relative (and absolute) risk reduction is similar across baseline systolic blood pressure levels from less than 120 mm Hg to more than 170 mm Hg, extending observations from epidemiological studies."
"In agreement with previous reports, antihypertensive treatment appears to reduce incident stroke and heart failure by a greater extent than ischaemic heart disease. However, the reported benefit at low entry systolic blood pressure in patients with a high proportion (75%) of ischaemic heart disease suggests that the risk of blood pressure lowering in this group of patients (ie, a J-curve for risk) might not be a problem in most patients.
"Of note, this systematic review could not include all eligible trials, which is an inherent limitation of all individual participant data meta-analyses. However, the investigators assessed the risk of acquisition bias, and also did sensitivity analyses excluding trials, without important effects on their findings. The findings might not be generalisable to patient groups with concomitant conditions not studied in these analyses (eg, heart failure).
"The similar relative benefits of treatment in primary and secondary prevention presented in the study by the BPLTTC indicate that the cardiovascular risk of an individual will be a major determinant of the absolute benefit of treatment, confirming the importance of risk assessment in individual patients.
"These findings have important implications for clinical practice, and suggest that antihypertensive treatment might be considered for any person for whom the absolute risk for a future cardiovascular event is sufficiently high. This suggestion calls for simple, reliable multivariable risk prediction tools made readily available in the electronic health record systems used by health-care providers. The use of patient self-reported computerised medical history taking could facilitate such development.11 Taken together, decisions about offering people antihypertensive treatment are all about cardiovascular risk reduction."
Dr Sir Nilesh Samani, medical director for the British Heart Foundation, said this study "again emphasises the importance of controlling blood pressure as well as possible, to reduce the risk of heart and circulatory diseases".
"The benefits of lowering blood pressure are there whether you have pre-existing heart disease or not, and this study shows that lowering blood pressure – even if it is in the normal range – is associated with fewer heart attacks and strokes," Samani said.
"This doesn't mean we should treat everyone with blood pressure-lowering drugs. If someone already has a low risk of heart disease, a 10% reduction in their blood pressure may only carry a small direct benefit," Samani added. "Ultimately, the decision to treat blood pressure and the target level to aim for is something that requires a conversation between the patient and the doctor. It’s also important to remember that blood pressure can be improved by means other than medication such as exercise and losing weight."
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
The Blood Pressure Lowering Treatment Trialists' Collaboration
Published in The Lancet on 1 May 2021
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.
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.
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 participants 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.
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.
British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School
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