Background
There is controversy over whether the threshold for blood pressure-lowering treatment should be different between people with and without type 2 diabetes. Our objective was to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by state. of type 2 diabetes, as well as according to initial levels of systolic blood pressure.
Methods
We performed a single-stage, individual participant-level data meta-analysis of major randomized controlled trials using the Blood Pressure Lowering Treatment Trials Collaboration dataset. Trials with information on baseline status of type 2 diabetes were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus standard blood pressure-lowering strategy, and reported at least 1000 person-years of follow-up in each group.
Trials exclusively in participants with heart failure or on short-term treatments and acute myocardial infarction or other acute settings were excluded. We expressed the effect of treatment by 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as a primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischemic heart disease. fatal, or heart failure causing death or requiring hospitalization.
Cox proportional hazards models, stratified by trial, were used to estimate hazard ratios (HRs) separately by baseline type 2 diabetes status, with additional stratification by baseline systolic blood pressure categories (in increments of 10 mm Hg from <120 mm Hg to ≥ 170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the duration of follow-up.
The effect of each of the five major classes of medications on lowering blood pressure, 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.
Results
We included data from 51 randomized clinical trials published between 1981 and 2014 with 358,533 participants (58% men), of whom 103,325 (29%) had known type 2 diabetes at baseline. The mean baseline systolic/diastolic blood pressure of people with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively.
Over a median follow-up of 4·2 years (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 relative treatment effect weaker 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]; p interaction=0·0013).
However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes due to the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence of heterogeneity of treatment effects by blood pressure. initial systolic blood pressure in neither group.
Consistent with the main findings, the analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with and without type 2 diabetes for any of the medication 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, the absolute effects were similar .
The difference in relative risk reduction was not related to baseline blood pressure or assignment to different drug classes. Therefore, the adoption of differential blood pressure thresholds, blood pressure lowering intensities, or classes of drugs used in people with and without type 2 diabetes is not justified .
Added value of this study
Blood pressure-lowering treatment reduced the risk of major cardiovascular events in people with and without type 2 diabetes in our meta-analysis of individual participant-level data from major blood pressure-lowering drug trials involving 103,325 participants with type 2 diabetes and 255,208 participants without type 2 diabetes.
However, the relative effects were weaker in people with established type 2 diabetes than in those without. However, because participants with type 2 diabetes had a higher risk of major cardiovascular events, the absolute risk reductions between the two groups did not differ.
Investigation of the underlying reasons for the heterogeneous relative effects suggested that the differences were not substantially influenced by baseline systolic blood pressure levels or the types of antihypertensive drugs used.
Implications of all available evidence
Our analyzes challenge the adoption of differential blood pressure thresholds, intensities, or drug classes in people with and without type 2 diabetes. This study calls for the elimination of specific blood pressure thresholds when selecting people with type 2 diabetes for antihypertensive therapy.
Money
British Heart Foundation, UK National Institute for Health Research and Oxford Martin School.
