The LANCET: Diabetes &
Endocrinology: Published on July, 2022
Diabetes is a major cause of death,
cardiovascular complications, and health-care burden worldwide.
People with type 2 diabetes who
have high blood pressure are at an increased risk of morbidity and death from
major cardiovascular events.
However, there are inadequate
randomised controlled trial data to determine if the benefit of blood
pressure-lowering treatment differs in people with type 2 diabetes versus those
without this metabolic condition.
Similarly, there is uncertainty around initiating blood pressure reduction therapy at a specific blood pressure threshold, particularly in people with normal or high-to-normal blood pressure levels.
TAKE-HOME MESSAGE
Do the effects of blood pressure–lowering treatment on the risk of major
cardiovascular events differ between people living with and without type 2
diabetes?
And should a specific blood pressure threshold to initiate blood
pressure–lowering treatment differ between people with and without type 2
diabetes?
This meta-analysis of 51 major
randomised controlled trials between 1981 and 2014 involving 358,533
participants investigated the effects of blood pressure lowering on the risk of
major cardiovascular events by type 2 diabetes statuses.
In both individuals with and
without type 2 diabetes, a 5–mm Hg reduction in systolic blood pressure
decreased the risk of major cardiovascular events in both groups, with a weaker
treatment effect in patients with type 2 diabetes. There was no difference in
absolute risk reductions between the two groups.
The results of the meta-analysis have a major implication for clinical
practice, as these indicate that there are no absolute differences in the risk
of major cardiovascular events between people with type 2 diabetes and those
without type 2 diabetes, so there is no need to apply differential blood
pressure thresholds, intensities of drug classes or allocate different drug
classes when controlling hypertension in people with and without type 2 diabetes.
However, these findings may or may
not apply to populations often not eligible for inclusion in intensive blood
pressure treatment trials, such as older adults with multi-morbidity.
Background: Controversy
exists as to whether the threshold for blood pressure-lowering treatment should
differ between people with and without type 2 diabetes. Study aimed to
investigate the effects of blood pressure-lowering treatment on the risk of
major cardiovascular events by type 2 diabetes statuses, as well as by baseline
levels of systolic blood pressure.
Methods: Authors
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 statuses
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. Authors 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.
Findings: Authors
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 and 153/88
mm Hg, respectively. Over 4·2 years median follow-up, 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 compared with those without type 2 diabetes. 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.
Interpretation: 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.
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