Cardiovascular disease is the main cause of death, in which hypertension as an important risk factor involved in the occurrence of cardiovascular and cerebrovascular events. The number of hypertensive patients in China has increased to 160 million, and the number of fatal strokes accounts for 44% of the deaths at the level of first-degree hypertension. 1997 has seen the number of deaths due to cerebrovascular disease jump to the first place in China, and the number of patients with cerebrovascular disease is about 3 million. Epidemiological surveys of cerebrovascular disease in 29 provinces and autonomous regions in China have shown that hypertension is one of the primary risk factors for cerebral infarction, and its incidence is five times higher than that of myocardial infarction. Therefore, active efforts to control blood pressure to the target blood pressure level are extremely important to prevent the occurrence of stroke and reasonable treatment after stroke to prevent re-stroke.
In the past decades, should blood pressure be lowered after a stroke? How should it be done? There has been controversy. The choice of antihypertensive drugs after stroke is important, and the timing of post-stroke antihypertensive treatment is also critical. It should be said that post-stroke control of hypertension is one of the most important strategies to prevent stroke recurrence. Recent studies suggest that the effectiveness of stroke prevention depends mainly on effective blood pressure control, although there are some differences between various drugs and programs, such as diuretics and calcium channel blockers have a better effect on stroke reduction than ACE inhibitors, but the difference is around 10%.
I. The primary prevention of stroke by antihypertensive therapy
The ultimate goal of antihypertensive therapy is to stop the development of vascular disease and reduce the incidence of cardiovascular events and mortality. In a large clinical trial of systolic hypertension in the elderly, it was found that aggressive long-term attainment of antihypertensive therapy with calcium antagonists reduced the risk of stroke by 42%, the risk of coronary heart disease by 26%, the risk of heart failure by 29%, and the risk of all cardiovascular events by 31%. Meanwhile, in recently published international clinical trial results, two classes of drugs, calcium antagonists and ACEI, were found to be more effective in reducing systolic hypertension in the elderly.
Three large clinical trials have been completed (HPOE Study – ACEI (ramipril) versus placebo, NORDIL Study – calcium antagonist (diltiazem extended-release tablets) versus traditional antihypertensive drugs (beta-blockers), LIFE Study – ARB (colesartan) versus beta-blockers (atenolol) The trial found that ACEI, ARB and calcium antagonists reduced blood pressure and further reduced stroke incidence by 32%, 25% and 20%, respectively, compared to the control group in reducing the decline in cardiovascular events. The benefits of ACEI, ARB, and calcium antagonists are particularly significant in high-risk elderly patients with hypertension, who have demonstrated significant organ-protective effects beyond BP reduction.
Currently, in vivo and in vitro trials of ARB, ACEI and Ca2 antagonists have demonstrated that they not only lower blood pressure, but also improve carotid and aortic dilation, endothelial function, and correct structural and functional abnormalities in blood vessels, reducing the incidence of cerebrovascular events and deaths after standard ACEI therapy plus angiotensin II receptor antagonist (ARB) treatment. death. The reduction of systolic blood pressure and the improvement of pulse pressure in the elderly have been recognized as part of blood pressure adjustment and need to be given adequate clinical attention. The improvement of vascular structure and function is of some significance in reducing the incidence of cardiovascular and cerebrovascular disease and death.
Second, antihypertensive treatment after stroke can be beneficial
The rate of disability after stroke is high, and the occurrence of repeated strokes can accelerate death after stroke. Therefore, active control of cardiovascular risk factors after stroke is extremely important to prevent the occurrence of further strokes. It is generally accepted that in early acute ischemic stroke, unless the blood pressure is very high (e.g., >180/105 mmHg), antihypertensive drugs should be suspended until the condition is stable. Otherwise, excessive blood pressure lowering can significantly reduce cerebral blood flow. After stabilization, blood pressure should be controlled to approximately 160/100 mm Hg. The combination of ACE inhibitors and thiazide diuretics reduces the rate of stroke recurrence. Evidence from clinical trials of the benefit of blood pressure lowering in patients with old strokes is strong. The Post-stroke Antihypertensive Treatment Study (PATS Study) in China, started in 1995, was a randomized, blinded, placebo-controlled trial that included 5665 patients with a mean age of 60 years.
Patients with a history of stroke or transient ischemic attack (TIA) were randomized to diuretic (indapamide 2.5 mg/d) antihypertensive therapy or placebo, and the endpoints analyzed were the incidence of fatal and nonfatal stroke. This study was conducted over 3 years and showed that the incidence of first fatal and non-fatal stroke at 3 years was 12.3% in the placebo group versus 9.4% in the indapamide group, with a relative risk of 0.71 (P=0.0009).
This trial suggests that the diuretic indapamide 2.5 mg/d in patients with a history of stroke or TIA resulted in a decrease in blood pressure, a 29% reduction in the incidence of fatal and nonfatal stroke, and good results in the prevention of stroke recurrence. The international multicenter Perindopril Prevention of Recurrent Stroke Study (PROGRESS), completed in 2001, was also a trial of post-stroke antihypertensive therapy for the prevention of recurrent strokes. The results showed a 28% reduction in the risk of re-stroke in the treatment group (P<0.001).
In an analysis of the PROGRESS trial, it was found that the use of perindopril alone after stroke resulted in a 5/3 mm Hg reduction in blood pressure and only a 5% reduction in the risk of re-stroke, and when combined with indapamide 2.5 mg, the blood pressure was reduced by 12/5 mm Hg, reducing the risk of re-stroke to 43%, thus suggesting that the benefit of lower blood pressure after stroke is greater in preventing re-stroke. In this regard, the US hypertension guidelines (JNC 7) state in the mandatory indications for hypertension that ACEI and thiazide diuretics can be used for post-stroke prevention and treatment.
The need to lower blood pressure after stroke depends on the blood pressure level before the stroke and the blood pressure status after the stroke.
Hypertension is the most important risk factor for stroke, and the chance of stroke is higher when the blood pressure is not lowered enough and when other risk factors (dyslipidemia and diabetes) are combined. 85% of hypertensive patients still have high blood pressure after stroke, and very few patients have normal blood pressure after stroke. Therefore, patients with a history of hypertension who have been using antihypertensive drugs for a long time and whose blood pressure is still high after a stroke need continuous antihypertensive treatment after a stroke, and for stroke patients whose blood pressure is already normal, the blood pressure can be observed for several weeks and months.
In addition to the blood pressure level, the state of cerebral blood flow after stroke should also be considered.
The level of cerebral blood flow is the key to determine whether blood pressure can be lowered during and after a stroke. In patients with long-term hypertension, cerebral blood flow is in compensatory up-regulation (rightward shift of the Berlet curve), and cerebral blood flow in the acute phase of stroke will be compensated abnormally, therefore, the requirements for lowering blood pressure in the acute phase of stroke are different from those in the chronic phase after stroke. The pressure reduction in the acute phase is based on the requirements of the Chinese stroke prevention and treatment guidelines, while the pressure reduction in the chronic phase needs to be based on the following points.
It is recommended that ultrasound and intracranial Doppler ultrasound of the carotid artery be performed in stroke patients when available to determine the stenosis of intracranial and extracranial vessels. The risk of stroke can occur if the blood pressure is too low. However, in hypertensive patients with carotid stenosis <70 mmHg, blood pressure can be lowered to below 140 mmHg.
If the patient develops intolerance, dizziness, headache, nausea, weakness and drowsiness during the process of blood pressure lowering, it is necessary to evaluate whether there is insufficient blood supply to the brain.
V. How much should blood pressure be lowered after a stroke?
What is the safest level of blood pressure for a patient who has had a stroke? What should be the target blood pressure? This has been a matter of clinical debate and controversy because of the paucity of evidence from clinical trials. According to the US hypertension guidelines (JNC 7), blood pressure after stroke should be controlled at 160/100 mmHg. The PROGRESS trial showed that antihypertensive therapy was beneficial in patients with cerebrovascular disease with or without hypertension after stroke, with a 32% reduction in stroke risk in the treatment group with hypertension and a 27% reduction in stroke risk in patients without hypertension (normotension). In patients with previous stroke or transient ischemic attack and a blood pressure of 140/90 mm Hg who were not treated (given placebo), the incidence of cardiovascular events was approximately 17% over 4 years.
This suggests that a moderate reduction in blood pressure levels in non-hypertensive patients with cerebrovascular disease is equally beneficial for secondary stroke prevention. In a subgroup analysis of the Asian population in the PROGRESS trial, it was also found that post-stroke BP compliance treatment (<140/90 mmHg) reduced the risk of reischemic stroke by 24% and the risk of rehemorrhagic stroke by 50% in the Asian population. Thus, the results of the PROGRESS clinical trial suggest that post-stroke BP lowering treatment with BP <140/90 mmHg (target BP) is safe. The European guidelines for hypertension published in 2003 state that BP should be lowered after stroke or TIA, and if the patient can tolerate it, it should be lowered regardless of the BP level.
VI. Evidence-based evidence and choice of antihypertensive drugs for lowering blood pressure after stroke
The disability rate after stroke is high, and death after stroke can be accelerated by repeated strokes. Therefore, active control of cardiovascular risk factors after stroke is extremely important to prevent the occurrence of further strokes. It is generally accepted that in early acute ischemic stroke, unless the blood pressure is very high (e.g., >180/105 mmHg), antihypertensive drugs should be suspended until the condition is stable. Otherwise, excessive blood pressure lowering can significantly reduce cerebral blood flow. After stabilization, blood pressure should be controlled to approximately 160/100 mmHg.
The combination of ACE inhibitors and thiazide diuretics reduces the rate of stroke recurrence. Evidence from clinical trials of the benefit of blood pressure lowering in patients with old strokes is strong. The evidence for BP lowering after acute stroke is from the ACCESS (Acute Candesartan Cilexetil Evaluation in Stroke) study, a randomized, double-blind, placebo-controlled trial evaluating the effect of ARBs (candesartan) on cardiovascular events by lowering BP within 72 hours of an ischemic stroke. The study was a randomized, double-blind, placebo-controlled trial in which 500 patients with acute ischemic stroke, with a mean stroke duration of 30 hours and mean blood pressure >180/105 mmHg on two blood pressure measurements at enrollment, were randomized to candesartan and placebo for 0 to 7 days of treatment, and to continue treatment with chelvesartan if blood pressure remained above 140/90 mmHg for 8 to 365 days of treatment, or to maintain placebo if blood pressure had normal maintain placebo treatment.
A total of 365 days of follow-up was achieved, and the study was terminated early when 339 patients were enrolled because the study objectives had been met during the follow-up. The results of the study showed that the incidence of death, loss of function, CVS and CNS endpoint events was 9.8% in the candesartan group (17 events in 166 patients) and 18.7% in the placebo group (31 events in 173 patients), with a 47.5% p<0.05 reduction in the risk of death and cardiovascular events associated with the candesartan group compared with placebo. The ACESS trial was the first to demonstrate the benefit of early blood pressure control with ARB class antihypertensive drugs in acute ischemic stroke.
VII. Evidence for antihypertensive treatment in the chronic phase after stroke
1. The Post-stroke Antihypertensive Treatment Study (PATS Study) in China was a randomized, double-blind, placebo-controlled trial that started in 1995 and included 5665 patients with a mean age of 60 years. Patients with a history of stroke or transient ischemic attack (TIA) were randomized to diuretic (indapamide 2.5 mg/d) antihypertensive therapy or placebo, and the endpoints were the incidence of fatal and nonfatal stroke. This study was conducted over 3 years and showed that the incidence of first fatal and non-fatal stroke at 3 years was 12.3% in the placebo group versus 9.4% in the indapamide group, with a relative risk of 0.71 (P=0.0009). This trial suggests that the diuretic indapamide 2.5 mg/d in patients with a history of stroke or TIA resulted in a decrease in blood pressure and a 29% reduction in the incidence of fatal and nonfatal strokes, with good results in preventing stroke recurrence.
This clinical trial was completed in 2001. 6105 patients (1520 in China) with a history of cerebrovascular disease were randomized to ACEI (perindopril 4 mg/d) plus indapamide 2.5 mg or placebo. mg or placebo for 4 years showed a 28% reduction in the risk of re-stroke in the treatment group (P<0.001). In an analysis of the PROGRESS trial, it was found that the use of perindopril alone after stroke resulted in a 5/3 mm Hg reduction in blood pressure and only a 5% reduction in the risk of recurrent stroke, and when combined with indapamide 2.5 mg, the blood pressure was reduced by 12/5 mm Hg, reducing the risk of recurrent stroke to 43%, thus suggesting that the benefit of preventing recurrent stroke is greater when blood pressure is lowered after stroke. In this regard, the US hypertension guidelines (JNC 7) state that ACEI and thiazide diuretics can be used for post-stroke prevention and treatment in the mandatory indications for hypertension.
The Profess (Prevention Regimen For Effedtively Avoiding Second Strokes) clinical trial will further evaluate the use of ARB (telmisartan 80 mg) and antiplatelet therapy with aspirin (ASA) and clopidogrel in patients with acute stroke from the perspective of antihypertensive and anticoagulation to reduce endpoint events.
The development of ischemic stroke is not only related to blood pressure levels but also to abnormalities in coagulation and fibrinolysis. The Profess study enrolled 15,500 stroke patients, aged >55 years, with ischemic stroke that occurred within 90 days. These patients were randomized to 4 groups by 2 × 2 analysis of cause, one with telmisartan 80 mg plus clopidogrel 75 mg and one with telmisartan 80 mg plus extended-release dipyridamole 200 mg and aspirin 25 mg BID, with a total of nearly 775O patients with ischemic stroke treated with ARB telmisartan 80 mg daily, and the primary endpoints entered into the endpoint analysis were time to recurrent stroke and secondary endpoints of vascular events, occurrence of hemorrhagic stroke and new onset of diabetes mellitus.
The trial will be conducted in 600 centers in 30 countries, with 6,000 stroke patients entering the study in China, and is expected to end in 2007. This study will provide new evidence for the use of ARB in the secondary prevention of stroke. We are looking forward to the results of the Profess clinical trial, which will provide new evidence for the use of ARBs in the reduction of blood pressure and cerebrovascular events. We look forward to the results of the Profess clinical trial, which will provide new evidence for the use of ARB to lower blood pressure and reduce arteriovascular events.
VIII. Which antihypertensive drug should be used in stroke patients?
Most of the current studies show that the onset of stroke and sudden cardiac death shows a diurnal rhythm. The peak onset of these diseases is between 6:00 a.m. and 12:00 p.m., and human physiological factors (e.g., blood pressure, heart rate, platelet coagulation, catecholamine release) follow a certain rhythm. Patients with hypertension have more non-spoon blood pressure changes (increased blood pressure load at night), and the occurrence of cardiovascular and cerebrovascular events is also more common in this group of patients.
Therefore, the ideal antihypertensive drug should be able to lower blood pressure smoothly within 24 hours and reduce the overall blood pressure level; deter the sudden rise of blood pressure in the early morning after waking up, so that hypertensive patients can safely pass the time of high cardiovascular and cerebrovascular events; at the same time, it can maintain the moderate decrease of blood pressure at night and restore the normal blood pressure pattern, so as to effectively protect the target organ function of heart and brain.
Patients with hypertension with stroke often have cerebral atherosclerosis as the main vascular structure change, and the main antiatherosclerotic treatment body antihypertensive drugs are more suitable for such patients. In the six categories (diuretics, β-blockers, CCB, ACEI, ARB and a-blockers) antihypertensive can be selected, antihypertensive drugs require stable blood pressure reduction and long-term effective blood pressure control.
1, as CCB drugs can partially enter the blood-cerebrospinal fluid barrier, reducing the calcium overload after cerebral ischemia, which is conducive to the protective effect of brain cells. Long-acting CCBs (Baxinotoxin, Lowe’s and Boydin) have the characteristics of stable blood pressure lowering and reducing blood pressure fluctuation, and also have the effect of anti-carotid atherosclerosis, which is suitable for hypertensive patients with stroke. The use of long-acting CCB in patients with stroke combined with coronary artery disease has a tendency to reduce the occurrence of re-stroke. The currently published ACTION study suggests that the use of Baysinto 60 mg daily in patients with coronary artery disease with hypertension resulted in a significant reduction in the occurrence of fatal strokes, P=0.01.
2, ACEI, ARB drugs and have reduced renin angiotensin activation, reduced cerebrovascular histologic lesions, and reduced re-stroke in patients with favorable stem stroke. The published PROGRESS trial has shown that antihypertensive therapy is beneficial for color enhancement in patients with cerebrovascular disease with or without birth after stroke, with birth, the risk of stroke was reduced by 32% in the treatment group, and antihypertensive therapy in stroke patients without hypertension (normotension) also reduced the risk of stroke by 27%. the Life study also suggested that the subgroup of patients with left ventricular hypertrophy with stroke in the presence of birth with ARB treatment with colesartan significantly nourished the occurrence of re-stroke.
3, the combination of drugs recommended for stroke patients In order to achieve a smoother lowering of blood pressure in stroke patients, the combination of drug therapy is often used clinically, generally in the form of combination: ACEICCB therapy, or ACEI or ARB diuretic therapy, ACEI or ARBCCB diuretic therapy. In patients with sympathetic activation (fast heart rate) patients can be treated with additional beta-blockers.
It is worth mentioning that it is wrong to use oral nifedipine for acute antihypertensive treatment in stroke patients with fluctuating increased blood pressure. If you, as a physician, judge that such increased blood pressure after stroke will bring risk of cardiac and cerebral events to patients, you should take intravenous antihypertensive drugs to carefully adjust blood pressure to stability, while oral nifedipine for acute antihypertensive treatment will increase the risk of reinfarction, so both Chinese and international birth Therefore, both Chinese and international guidelines for the prevention and treatment of cerebrovascular disease include nifedipine as a contraindication to acute antihypertensive drugs after stroke.
In summary, the problem of post-stroke blood pressure lowering is a complex phenomenon, but as long as the mastery of good treatment and treatment principles stroke patients reasonable blood pressure lowering will enable patients to get greater benefit.