Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial

Mant J, et al assessed whether using intensive blood pressure targets leads to lower blood pressure (BP) in a community population of people with prevalent cerebrovascular disease.
They observed that aiming for target below 130 mm Hg rather than 140 mm Hg for systolic BP in people with cerebrovascular disease in primary care led to a small additional reduction in BP. Active management of systolic BP in this population using a <140 mm Hg target led to a clinically important reduction in BP.1

This group also assessed the efficacy and safety of intensive BP-lowering strategies. They identified 19 trials including 44,989 participants, during a mean 3•8 years of follow-up (range 1•0-8•4 years). This meta-analysis showed that patients in the more intensive BP-lowering treatment group had mean BP levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive BP-lowering treatment achieved relative risk reductions for major cardiovascular events (14% [95% CI 4-22]), myocardial infarction (13% [0-24]), stroke (22% [10-32]), albuminuria (10% [3-16]), and retinopathy progression (19% [0-34]). The reduction in major cardiovascular events was consistent across patient groups, and additional BP-lowering had a clear benefit even in patients with systolic BP lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes.2

Previous studies determined the subgroup specific associations between usual BP and risk of peripheral arterial disease, and to examine the relation between peripheral arterial disease and a range of other types of vascular disease in a large contemporary cohort. They observed that a 20 mm Hg higher than usual systolic BP was associated with a 63% higher risk of peripheral arterial disease (hazard ratio 1.63) and peripheral arterial disease was associated with an increased risk of 11 different vascular events, including ischaemic heart disease, heart failure, aortic aneurysm, and chronic kidney disease, but not haemorrhagic stroke.3 Therefore, to control BP is important to prevent vascular injury.

The next question is to define the most optimal BP target level in people with hypertension. Because observational studies with a low risk of confounding have shown a linear relationship between BP and cardiovascular risk down to 115/75 mm Hg.4 To answer in people with diabetes, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was performed and showed surprising results- no significant overall difference in cardiovascular events between patients with type 2 diabetes assigned to a systolic BP target of less than 120 mm Hg and those assigned to a target of less than 140 mm Hg.5 Therefore, the Eighth Joint National Committee took a targeted approach to consideration of previous trials and concluded that systolic BP targets should be below 140 mm Hg, or below 150 mm Hg in those 60 years of age or older.6

Nonetheless, the Systolic Blood Pressure Intervention Trial (SPRINT) reported that among patients at high risk for cardiovascular events but without diabetes, targeting a systolic BP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group.7 Its editorial disclosed that the effects on individual outcomes in SPRINT and the ACCORD trial are generally consistent and the main differences were that the ACCORD trial had less statistical power than SPRINT, and its primary outcome included a higher proportion of events that are less sensitive to BP reduction and suggested current guidelines and guideline processes require revision.8

Now are Prevention After Stroke-Blood Pressure (PAST-BP) and SPRINT studies enough to finish this debate regarding optimal BP targets? Some observational studies with a greater potential for confounding, involving persons at increased risk, have suggested a J-shaped curve. Indeed, Brunstrom M, et al reiterated this fact. They evaluated the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels and observed that antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic BP more than 140 mm Hg. If systolic BP is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.9 Furthermore, physicians should keep in mind rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive treatment group than in the standard-treatment group.7 When we go over even PAST-BP study with caution, patients set a target of <130 mm Hg or a 10 mm Hg reduction if initial BP was <140 mm Hg achieved lower systolic blood pressures than those set a target of <140 mm Hg. However, the difference was small (3 mm Hg) in the context of the reduction in BP observed in both arms (13 mm Hg and 16 mm Hg). Active management of BP after stroke/transient ischaemic attack is more important than the target that is set.1

Physicians are now in chaos because of recent controversial clinical trials. Various strategies to reduce residual cardiovascular risk in hypertensive patients included treating BP to lower target goals and using different classes of anti-hypertensive medications, however still considerable residual risk remained. In contrast, controlling hypercholesterolemia in hypertensive patients by statins is very effective in reducing residual cardiovascular risk by 35% to 40%.10 Also, cross-talk between hypercholesterolemia and rennin angiotensin system (RAS) exists at multiple steps of insulin resistance and endothelial dysfunction. In this regard, combined therapy with statins and RAS blockers demonstrate additive/synergistic effects on endothelial dysfunction and insulin resistance in addition to lowering cholesterol levels and blood pressure when compared with either monotherapy in patients.11,12 This is mediated by both distinct and interrelated mechanisms. Therefore, combined therapy with statins and RAS blockers may be important in developing optimal management strategies in patients with hypertension, hypercholesterolemia, diabetes, metabolic syndrome, or obesity to prevent vascular risk.13-15 Nonetheless, a current pretty low incidence taking statins in hypertensive patients is very disappointing.

REFERENCES
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2. Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet 2016;387:435-43.

3. Emdin CA, Anderson SG, Callender T, et al. Usual blood pressure, peripheral arterial disease, and vascular risk: cohort study of 4.2 million adults. BMJ 2015;351:h4865.

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