Chapter 7: Blood pressure in acute stroke

Acute haemorrhagic stroke

High blood pressure is common in acute intracerebral haemorrhage and is associated with haematoma expansion, death and less neurological recovery. Treatment depends partly on whether intervention begins within or after six hours of symptom onset. Earlier randomised trials suggested that, in people treated within six hours, reducing very high systolic pressure toward 140 mmHg could reduce disability and death, whereas reducing it below 140 mmHg did not add benefit and in one trial increased adverse renal events.

A continuous association between the magnitude of pressure reduction during the first 24 hours and functional neurological improvement was found in an analysis of 3,809 people whose treatment began a mean 3.6 hours after onset. A meta-analysis of five RCTs also found functional improvement when people with small-to-moderate haematomas were reduced below 140/90 mmHg. More intensive early targets may therefore be reasonable in selected patients.

Excessive lowering remains a concern. A pooled analysis of INTERACT2 and ATTACH-2 participants found worse outcomes when systolic pressure fell by more than 60 mmHg compared with a smaller fall. For systolic pressure below 220 mmHg when treatment begins more than six hours after onset, evidence is less clear. A recent individual-participant meta-analysis of 16 studies involving 6,221 people found that a moderate reduction, approximately 12.1 mmHg over several hours, reduced haematoma expansion but did not clearly improve functional recovery. Slow and moderate reduction is therefore preferable to an intensive numerical target.

Less evidence is available when systolic pressure exceeds 220 mmHg. Meta-analysis and secondary RCT analyses suggest possible functional benefit from reduction below 180 mmHg, while ATTACH-2 found more clinical deterioration when pressure above 220 mmHg was reduced below 140/90. A cautious reduction toward systolic pressure below 180 mmHg, often with supervised intravenous treatment, is therefore a reasonable approach.

Acute ischaemic stroke

The benefit of lowering pressure is less clear in acute ischaemic stroke. Initial values are often high or very high and usually fall spontaneously over the first 48–72 hours. Although higher pressure in this period is associated with worse clinical or neurological outcomes, the association cannot automatically be translated into drug treatment: most RCTs and meta-analyses have not shown lower mortality or disability from early reduction.

Trial evidence is difficult to generalise because studies included different stroke mechanisms—lacunar stroke, large-vessel occlusion and cardioembolism—, different ages and comorbidities, different spontaneous changes during the first hours, and different infarct volumes and intracranial pressures. These differences may conceal benefit or harm in particular subgroups.

A practical approach is cautious, slow reduction, about 15% during the first 24 hours, when pressure is markedly elevated at or above 220/120 mmHg. In the first 72 hours, avoid routine lowering when pressure is below 220/120 because reliable benefit has not been shown.

Patients who are eligible for or have received reperfusion, intravenous thrombolysis or mechanical thrombectomy, are a special group. Observational data link high pressure with intracranial haemorrhage after these procedures. Pressure should be reduced below 180/105 mmHg for at least the first 24 hours and kept stable. A meta-analysis of seven studies involving 5,874 people found a 20% increase in intracranial haemorrhage and a 12% increase in worse neurological outcomes for every 10-mmHg pressure increase. Lowering systolic pressure below 130 mmHg has not shown benefit.

In clinically stable people whose pressure remains above 140/90 for more than three days after an acute ischaemic stroke, starting or restarting antihypertensive treatment should be considered.

Previous stroke or transient ischaemic attack

RCTs in clinically stable hypertensive people with previous stroke or TIA show that lowering pressure reduces recurrent stroke and other cardiovascular or cerebrovascular events. Treatment should therefore begin or resume after several days, once the clinical situation has stabilised, or immediately after a TIA in previously untreated or treated people with hypertension.

No placebo-controlled trial has established whether treatment also prevents recurrence when pressure is high-normal or lower. The optimal target is also uncertain, but across trials and meta-analyses the recurrent-stroke risk within a systolic range of 120–140 mmHg was lower as achieved systolic pressure became lower.

These data apply mainly to people with a mean age below 70 years. Secondary prevention targets should be individualised according to function, frailty, cognition and other clinical circumstances. A reasonable first goal is below 140/80 mmHg, followed when tolerated and monitored by a goal below 130/80 mmHg. Systolic pressure below 120 mmHg should be avoided.

Large RCTs demonstrated stroke prevention with several drug regimens. Comparative trials and meta-analyses suggest that beta blockers are less effective for stroke prevention than the main alternative classes, although they still provide significant protection in some trials. Their cerebral effects are not fully understood, and there is no evidence that beta blockers directly damage the brain or impair cerebral autoregulation.

In a large meta-analysis, stroke risk did not differ substantially between beta blockers and renin–angiotensin blockers or diuretics, but was higher than with calcium-channel blockers. This may reflect a modestly stronger stroke-protective effect of calcium-channel blockers. Because recurrent stroke is more common than myocardial infarction after stroke, beta blockers should not be the preferred drugs for secondary stroke prevention unless a specific indication or comorbidity supports them.

Cognitive impairment and dementia

Dementia incidence has increased over the past 25 years, largely because populations are ageing. It is more common in women and is the fifth leading cause of death worldwide. Epidemiological and clinical studies show that midlife hypertension predicts later cognitive decline, Alzheimer disease and vascular dementia. Long-term cumulative pressure independently predicts later decline in cognitively healthy adults.

The mechanism includes remodelling of small cerebral vessels, white-matter lesions, microbleeds and lacunar infarcts. Large-artery stiffness and pulsatile flow contribute to small-vessel disease and reduced flow in cognitive regions such as the basal ganglia and hippocampus. Routine hypertension assessment should therefore consider cognitive impairment at least from age 65 onward.

Evidence for cognitive benefit from pressure lowering was previously inconsistent. A recent meta-analysis of five RCTs involving 28,008 people, using pooled individual-participant data over a mean 4.3-year follow-up, found a 13% reduction in incident dementia with an average 10/4-mmHg systolic/diastolic reduction. Several studies also found that intensive control below 130 mmHg systolic slowed white-matter lesions and global cognitive decline.

Whether one drug class is superior remains debated. Observational and registry data suggest that ARBs, dihydropyridine calcium-channel blockers and thiazide or thiazide-like diuretics may be more favourable than ACE inhibitors, non-dihydropyridine calcium-channel blockers and beta blockers. Post-hoc analyses of PreDIVA and SPRINT-MIND found approximately 24% fewer incident cognitive impairments with the former group. Prospective controlled trials are still needed to confirm this observation. Current evidence supports treating hypertension and maintaining good control during later midlife and older age to reduce the risk of cognitive decline and dementia.