Professor Zhao Xingquan: Early stroke blood pressure control (1): Early blood pressure management before and in the hospital

Background information

Background information Background information

For post-stroke blood pressure management, it is clinically inclined to maintain a hypertensive state in patients with cerebral infarction, and to lower blood pressure in patients with cerebral hemorrhage
.

However, the following problems currently exist:

Effectiveness: Research data does not confirm the effectiveness of this approach;

Target blood pressure: failed to provide a consistent optimal target value for blood pressure;

Timing: There is still controversy about when to lower the pressure;

Severe and special cases: Most studies only involve very few severe patients or patients with complex comorbidities
.

The systolic blood pressure in the acute phase of ischemic stroke patients is similar to the daily level before the illness; patients with cerebral hemorrhage have a tendency to increase blood pressure several days to several weeks before the onset of the onset, and the blood pressure will increase significantly within 3 hours after the onset of the onset, and it will appear within 24 hours after the onset of the onset.
Significantly down
.

Under normal circumstances, the brain's self-regulation ability can tolerate a certain range of fluctuations in blood pressure, thereby maintaining normal cerebral blood flow within a wide range of cerebral perfusion pressure, and the adjustment range of mean arterial pressure (MAP) is 50-150 mmHg

There are divergent views in current research on whether it is reasonable to lower blood pressure in the acute phase of stroke:

Content directory

Content directory

one

one

Antihypertensive in the acute phase of ischemic stroke

Antihypertensive in the acute phase of ischemic stroke

Early blood pressure management before and in the hospital

Early blood pressure management before and in the hospital

Blood pressure management after intravenous thrombolysis

Blood pressure management after intravenous thrombolysis

Blood pressure management after endovascular treatment

Blood pressure management after endovascular treatment

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two

Blood pressure reduction in acute phase of hemorrhagic stroke

Blood pressure reduction in acute phase of hemorrhagic stroke

Strengthen the safety of blood pressure reduction

Strengthen the safety of blood pressure reduction

Target value for depressurization

Target value for depressurization

Perioperative blood pressure reduction

Perioperative blood pressure reduction

Antihypertensive in the acute phase of ischemic stroke

Antihypertensive in the acute phase of ischemic stroke Antihypertensive in the acute phase of ischemic stroke

The final infarct size of ischemic stroke largely depends on the compensatory perfusion of the collateral circulation.
The increase of systolic blood pressure in patients with cerebral infarction is related to the improvement of collateral circulation.
70% to 80% of patients will have reflex systolic blood pressure increase.
, This can be regarded as a physiological response
.

The magnitude and duration of the reflex blood pressure increase may indicate a more severe stroke and a worse prognosis

The spontaneous decrease in blood pressure after stroke seems to be related to revascularization
.

Previous studies have shown that blood pressure usually drops within 1 week of onset, but significant fluctuations may occur during this period

Early blood pressure management before and in the hospital

Pre-hospital and early blood pressure management in the hospital Pre-hospital and early blood pressure management in the hospital

1.
Pre-hospital blood pressure management for cerebral infarction

1.
Pre-hospital blood pressure management for cerebral infarction

RIGHT-Ⅱ Trial (published in 2019): A randomized, controlled, single-blind, multi-center prospective phase III clinical study involving 1149 suspected hyperacute stroke patients with systolic blood pressure> 120 mmHg (mean age 73 years, 52 males) %), randomly divided into blank control group (n=581) and nitroglycerin group (n=568)
.

The study found that prehospital application of nitroglycerin patch to lower blood pressure does not improve the overall outcome of acute stroke patients, and cannot reduce the incidence of post-stroke disability; the earlier the use of nitroglycerin, the worse the effect (receiving treatment within 1 h is negative, 1~ There is a negative trend between 2 hours and a neutral trend above 2 hours)

MR ASAP trial (published in 2021): negative result, terminated early
.

326 patients (56 cases of cerebral hemorrhage) with suspected stroke in the prehospital setting (within 3 hours after the onset of symptoms) were enrolled.

2.
RCT for antihypertensive in the acute phase of cerebral infarction

2.
RCT for antihypertensive in the acute phase of cerebral infarction

COSSACS study: 763 patients (mainly ischemic stroke, 5% primary cerebral hemorrhage) were randomly divided into two groups: one group continued to receive antihypertensive drugs 2 weeks after the stroke, and the other group suspended antihypertensive drugs After 2 weeks, the systolic blood pressure of the continued medication group was reduced by 13 mmHg compared with the discontinuation group, but there was no difference in the incidence of primary endpoint events
.

SCAST study: 2029 patients with subacute stroke (about 85% ischemic stroke, 15% hemorrhagic stroke) were randomly divided into two groups: ARB group vs placebo group, each taking 7 days
.

At the same time, antihypertensive drugs (non-blind) were given based on experience, and more than 1/4 patients received such drugs

Chinese Acute Ischemic Stroke Antihypertensive (CATIS) Study: 4071 patients were enrolled.
Among them, 2038 patients in the antihypertensive treatment group received antihypertensive treatment 15 hours after the onset of onset, which reduced blood pressure by 10% to 25% within 24 hours.
The blood pressure gradually dropped below 140/90 mmHg within 7 days
.

Compared with the control group, the absolute blood pressure of the antihypertensive treatment group decreased by 8.

CATIS research design and implementation have some limitations

CATIS research design and implementation have some limitations

Non-blind drug intervention can easily lead to evaluation bias;

The classification of ischemic stroke subtypes does not use standard methods;

The severity of stroke is relatively mild.
The NIHSS median score = 4 points, which is lower than the severity of traditional stroke clinical trials.
Therefore, 2/3 of the patients in the control group reach the main prognostic indicators (survival or sound), and control of blood pressure is less likely to be beneficial.
；

Excluding patients with known cervical and cerebral macrovascular disease, limiting the universality of these stroke-prone patients;

The median time for randomization is about 15 hours after stroke, which is in the subacute phase rather than the acute phase within 1 to 10 hours after the occurrence of ischemic stroke
.

The secondary analysis of the CATIS study: After the onset of acute ischemic stroke, for people who already have high blood pressure, continued antihypertensive treatment may have the effect of preventing recurrence of stroke; in patients with a history of hypertension, after the onset of stroke The risk of stroke recurrence and vascular events were reduced by 56% and 34%, respectively, in those who started antihypertensive treatment as soon as possible
.

For people who have not had high blood pressure in the past, it should be based on their clinical conditions to decide whether to initiate antihypertensive therapy
.
Among patients without a history of hypertension, antihypertensive treatment was effective in stroke recurrence (OR 3.
43, 95%CI 0.
94-12.
55, P=0.
06) and vascular events (OR 1.
91, 95%CI 0.
75~4.
83, P= 0.
17) The occurrence risk has no obvious impact
.
In general, the initiation of antihypertensive therapy immediately after the onset of acute ischemic stroke is not related to the composite end point of death and significant disability (modified Rankin scale score ≥ 3 points) at 2 weeks after the onset of the stroke or death at discharge
.

Subgroup analysis of the ENOS trial (safety and benefits of lowering blood pressure in patients with severe internal carotid artery stenosis in the acute phase): Patients with internal carotid artery stenosis in the ENOS trial were divided into <30% and 30%~50% according to the degree of unilateral stenosis , 50%~70% and ≥70% stenosis group, analyze whether the acute phase nitroglycerin transdermal patch can improve the prognosis, and whether stopping the antihypertensive treatment for patients with a history of antihypertensive therapy will affect the prognosis
.
Patients with high systolic blood pressure (140-220 mmHg) within 48 hours of the onset of acute ischemic stroke were randomly assigned to the nitroglycerin group (5 mg*7 d) and the patch-free group
.
The results showed that the prognosis of patients with internal carotid artery stenosis ≥70% was significantly worse than that of patients with stenosis less than 30%; in the nitroglycerin group with internal carotid artery stenosis ≥70%, mRS displacement analysis showed that the mortality and disability rate were reduced (OR 0.
56 , 95%CI 0.
34~0.
93, P=0.
024); in the 50%~70% internal carotid artery stenosis group, continued antihypertensive treatment is associated with poor prognosis (declined cognitive function, depression, disability, etc.
); for the only 97 cases In patients with bilateral internal carotid artery stenosis, nitroglycerin and continued antihypertensive therapy did not affect the prognosis
.

3.
Timing and blood pressure goals for initiating antihypertensive therapy in the acute phase

3.
Timing and blood pressure goals for initiating antihypertensive therapy in the acute phase

The results of a meta-analysis involving 11 studies and 38 742 patients showed that it supports the use of antihypertensive drugs at least 48 hours after stroke or TIA to reduce the risk of stroke recurrence; current evidence mainly comes from clinical trials of ACEI and diuretics ; Current evidence is unable to provide the best blood pressure goal after stroke or TIA, but it is indeed observed that intensive antihypertensive therapy can reduce the risk of stroke recurrence and serious vascular events
.

Research conclusions on blood pressure reduction in acute ischemic stroke:

4.
Blood pressure control in patients with acute ischemic stroke (guidelines and consensus)

4.
Blood pressure control in patients with acute ischemic stroke (guidelines and consensus)

AHA/ASA 2014 Guidelines: The appropriate time to restart long-term antihypertensive therapy after acute ischemic stroke has not yet been determined
.

The 2017 American ACC/AHA Hypertension Guidelines: For hypertensive patients who have previously received antihypertensive therapy, restarting antihypertensive therapy in the first few days after a stroke or TIA can reduce the risk of recurring strokes and other vascular events
.
(Ⅰ, A)

AHA/ASA 2018 guidelines: It may be reasonable to reduce blood pressure by 15% within the first 24 hours after the onset of stroke
.
(Ⅱb, C-EO recommended level is lower)

Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018: If the condition is stable after stroke, if the blood pressure continues to be ≥140/90 mmHg and there is no contraindication, you can resume the antihypertensive drugs taken before the onset of the disease or start antihypertensive treatment a few days after the onset , But did not clearly specify the start-up depressurization time
.

2019 NICE guideline: In the presence of one or more of the following severely complicated hypertensive emergencies, it is recommended to treat patients with acute ischemic stroke: ①hypertensive encephalopathy; ②hypertensive nephropathy; ③hypertensive heart failure / Myocardial infarction; ④ Aortic dissection; ⑤ Pre-eclampsia/eclampsia
.
For patients who will undergo intravenous thrombolysis and patients who plan to undergo intraarterial treatment without intravenous thrombolysis, consideration should be given to lowering their blood pressure to 185/110 mmHg or lower
.

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