Evid Based Med 2013;18:222-223 doi:10.1136/eb-2013-101302

Systematic review and meta-analysis

Meta-analysis shows limited benefit of lowering blood pressure below 130/80?mm?Hg in patients with type 2 diabetes
Farrukh M Koraishy, Aldo J Peixoto

Commentary on:
McBrien K, Rabi DM, Campbell N, et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2012;172:1296–303.

Context

Although lowering blood pressure (BP) to the standard target of 140/90?mm?Hg improves cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM), the benefits of more intensive lowering to <130/80?mm?Hg have not been conclusively demonstrated.
Despite this shortcoming, most current practice guidelines recommend this lower target.
Two meta-analyses of studies evaluating outcomes according to the level of BP achieved in patients with diabetes, or glucose intolerance demonstrated that tight BP control resulted in fewer strokes and albuminuria, but had no impact on other cardiovascular events or death.

Methods

The investigators evaluated five randomised clinical trials including 7312 patients with T2DM.
The studies compared a standard BP target (systolic BP (SBP) <140?mm?Hg in one study, or diastolic BP (DBP) <90?mm?Hg in four studies) to a more intensive one (SBP <120?mm?Hg in 1 study; DBP <75?mm?Hg in 3 studies, or <80 or <85?mm?Hg in 1 study).
Only studies evaluating mortality, myocardial infarction (MI) or stroke were included.
As a supplementary analysis, the authors meta-analysed another five randomised trials that compared BP targets <150–160/85–100?mm?Hg with historical BP control above these levels in 3093 T2DM patients.

Findings
Intensive BP control led to a significant decrease in stroke (risk ratio (RR) 0.65, 95% CI 0.48 to 0.86) but resulted in non-significant trends on mortality (RR 0.76, 95% CI 0.55 to 1.05) and MI (RR 0.93, 95% CI 0.8 to 1.08). Despite the significant 35% lower risk of stroke, the absolute risk reduction was low (?1%, 95% CI ?2% to 0%) given the low overall incidence of stroke.
Intensive BP control was associated with increased risk for serious adverse events (3.3% vs 1.7%, p<0.001), particularly hypotension and acute fall in renal function.
In the supplementary meta-analysis, the results demonstrated significant risk reduction in mortality, stroke and MI with BP lowering to the range of 142–153/70–84?mm?Hg.

Commentary
This was a well-performed meta-analysis including only trials that compared prespecified BP goals that are similar to the current BP guidelines, hence distinguishing it from the previous two meta-analyses.
Its major limitation relates to the paucity of large, well-conducted trials comparing BP targets in T2DM. Furthermore, one single study (Action to Control Cardiovascular Risk in Diabetes, ACCORD3) was responsible for 65% of all participants, 69% deaths, 83% MIs and 48% strokes.

The evidence that SBP reduction below 130?mm?Hg in patients with diabetes seems to have a benefit in stroke but not in MI might be explained by differences in the physiology of the two circulations. While coronary blood flow is highly dependent on DBP and its autoregulation is impaired in left ventricular hypertrophy (LVH) and coronary artery disease (CAD), the cerebral circulation has more robust autoregulatory mechanisms and is less affected by low BP; possibly the explanation for the ‘J-curve phenomenon’ linking low DBP to increased risk for MI but not stroke.

When one attempts to translate these findings in practice, several points need to be discussed.
First, based on the supplementary meta-analysis, clinicians must strive to decrease the BP to levels at least in the 140/90?mm?Hg range; failure to do so results in excess risk of death, stroke, MI and microvascular complications.
Second, largely based on the results of ACCORD, SBP reduction to <120?mm?Hg results in increased serious adverse events, thus limiting the enthusiasm for aggressive BP reduction even though there was a non-significant trend towards reduction of all endpoints, especially because the absolute risk reductions were small. The available data do not allow comments related to intermediate SBP levels in the 120–130?mm?Hg range.
Third, tighter BP control demands the use of more medications, which is associated with increased costs and decreased adherence.
Finally, given the greater relative benefits in stroke prevention, it will be important to develop methods to define stroke risk in T2DM so that patients at high risk can be treated to lower BP targets, especially when not accompanied by LVH or CAD. Current evidence on this is sparse;

older age, hypertension, diabetic nephropathy and prior strokes are associated with increased risk, but we were unable to identify any reliable risk prediction tool.
Based on current evidence, most T2DM patients should have their BP controlled to the 130–140/80–85?mm?Hg range.

G Mohan.