Heart and God masters talk about the breakthrough in the treatment of stroke combined with hypertension!

*Only for medical professionals to read.
Reference Angiotensin receptor enkephalinase inhibitor (ARNI) has been approved for hypertension indications, bringing a breakthrough change in the field of primary and secondary prevention of stroke
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Message from Experts Ge Junbo, Academician of Zhongshan Hospital Affiliated to Fudan University Actually, ARNI is no longer limited to the treatment of heart failure, but has an effect on the entire cardiovascular event chain
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It can prevent heart failure as early as possible by improving cardiac remodeling .

The official approval of sacubitril and valsartan for hypertension indications will not only benefit the majority of hypertensive patients in China, but will also have a positive impact on the revision of the guidelines and other countries in the world
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Congratulations again to the official approval of Shacubatril and Valsartan! From high blood pressure to heart failure, Professor Dong Qiang from Huashan Hospital Affiliated to Fudan University, sacubitril and valsartan helped to achieve the full management of heart and kidney events.
While achieving fruitful results in the field of heart failure, it also showed the unique effect of lowering blood pressure
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The approval of the antihypertensive indication also adds a good antihypertensive drug to the blood pressure management of stroke patients, helping to reduce the risk of end-point events in patients with high risk of cardiovascular and cerebrovascular events
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Hypertension is one of the most important risk factors for stroke, and strengthening and optimizing blood pressure control play a pivotal role in the primary and secondary prevention of stroke
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So what changes will the approval of ARNI hypertension indications bring to the prevention and treatment of stroke? Compared with other kinds of antihypertensive drugs, what is new in ARNI? Stroke management, blood pressure first! Hypertension is the most important risk factor for stroke and transient ischemic attack (TIA)
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In patients with recent ischemic stroke, the diagnosis rate of hypertension is as high as 70% [1]
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Whether in primary or secondary stroke prevention, blood pressure management occupies an important position
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As pointed out in the 2014 China Guidelines for Secondary Prevention of Ischemic Stroke and TIA[1], patients with ischemic stroke or TIA who have not received antihypertensive therapy in the past, if the systolic blood pressure is ≥140 mmHg or the diastolic blood pressure is ≥90 a few days after the onset mmHg, antihypertensive therapy should be initiated
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In patients with ischemic stroke or TIA who have a history of hypertension and have been treated with antihypertensive drugs for a long time, if there is no absolute contraindication, antihypertensive therapy should be restarted a few days after the onset
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Inconsistent with the current status of the guidelines’ active recommendations, the control rate of hypertension patients in China still needs to be improved
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The China PEACE study (2014~2017) indicated that the awareness, treatment and control rates of Chinese hypertension patients were only 36.
0%, 22.
9% and 5.
7%, respectively [2]
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Among stroke patients with a clear history of hypertension, only 21% have achieved blood pressure control [3], and the current situation needs to be improved
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If all hypertensive patients are treated, China will reduce 690,000 strokes each year, and the disease and economic burden will be significantly reduced [4]
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ARNI, what is the difference in the blood pressure reduction effect? Compared with several types of antihypertensive drugs that have been approved in the past, what are the unique advantages of ARNI? Let's do it one by one
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■ Strong blood pressure reduction An Asian randomized double-blind trial of 1438 patients ≥18 years of age with active drugs as a control, and mainly Chinese hypertensive population, suggested that compared with the dose of Olmesartan 20 mg qd, The 200 mg qd dose of sacubitril and valsartan can reduce the sitting systolic blood pressure (msSBP) by 2.
33 mmHg and the sitting diastolic blood pressure (msDBP) by 1.
24 mmHg [5] (Figure 1)
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Figure 1 Sacubitril and valsartan is more effective than olmesartan in lowering blood pressure.
Other studies have shown that compared with amlodipine 5 mg qd alone, the addition of sacubitril and valsartan 200 mg qd can make The 24-hour dynamic mean systolic blood pressure (maSBP), mean diastolic blood pressure (maDBP), and mean pulse pressure (maPP) were reduced by 13.
1 mmHg, 7.
7 mmHg, and 5.
3 mmHg, respectively [6] (Figure 2)
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Figure 2 Sacubitril and Valsartan combined with amlodipine is more effective in lowering blood pressure than amlodipine alone.
■ "Smart" blood pressure reduction, suitable for analysis of different baseline blood pressure populations.
The included object is PARAGON with ejection fraction preservation heart failure (HFpEF) -HF research will also find that for patients with baseline systolic blood pressure ≥140 mmHg, sacubitril and valsartan can significantly reduce blood pressure; for patients with baseline systolic blood pressure <120 mmHg, sacubitril and valsartan can be Keep its blood pressure at a stable level (Figure 3) [7]
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Figure 3 High baseline blood pressure significantly lowered blood pressure, low baseline blood pressure remained stable, sacubitril and valsartan lowered blood pressure more "smart" (SBP: systolic blood pressure) analysis of the results of the PARADIGM-HF test also showed consistent conclusions
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Such antihypertensive features bring higher safety and may be more suitable for stroke patients
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■ 24-hour long-lasting blood pressure lowering the risk of stroke The application of 24-hour, long-lasting blood pressure lowering drugs can reduce nocturnal hypertension and morning blood pressure peaks, and help reduce the risk of stroke and recurrence
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Clinical studies have shown that sacubitril and valsartan treatment for 12 weeks significantly reduces blood pressure for 24 hours, which is better than angiotensin receptor antagonist (ARB), and the nighttime blood pressure is lowered more significantly [8] (Figure 4)
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Fig.
4 Sarcubatril and Valsartan was treated for 12 weeks, which significantly reduced 24h blood pressure and night blood pressure, which was better than Olmesartan.
Another 8-week randomized controlled trial involving 1328 patients with hypertension between 18 and 75 years old [9] It is shown that compared with patients taking valsartan 160 mg qd, patients taking sacubatril and valsartan 200 mg qd have 24-hour dynamic systolic blood pressure, night-time average dynamic systolic blood pressure, night-time average dynamic diastolic blood pressure, and ambulatory pulse pressure respectively.
Reduce 3.
23 mmHg, 6.
03 mmHg, 3.
55 mmHg, 2.
48 mmHg more
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Compared with the 320 mg qd dose of valsartan, the 400 mg qd dose of sacubitril and valsartan can reduce the 24-hour dynamic systolic blood pressure, night average dynamic systolic blood pressure, and ambulatory pulse pressure by 5.
14 mmHg, 4.
53 mmHg, and 3.
95 mmHg, respectively.

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■ Unique vascular protection effect In addition to the renin-angiotensin-aldosterone system (RAAS), sacubitril and valsartan can also act on the natriuretic peptide system, so it has anti-arteriosclerosis, anti-vascular proliferation, and lower pulse Vascular protection such as pressure difference and anti-vascular fibrosis (Figure 5-7) [10-12]
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Compared with valsartan, it has a stronger effect on improving arteriosclerosis and is more suitable for stroke patients who need vascular protection
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Figure 5 Sacubitril and valsartan significantly reduce pulse wave velocity (PWV) and improve vascular fibrosis.
Figure 6 Sacubitril and valsartan significantly improve carotid artery intima-media thickness (IMT) and carotid arteriosclerosis.
7 Sacubitril and valsartan improve carotid plaque components, stabilize plaque and reduce plaque formation ■ Reduce the risk of end-point events.
Numerous studies have confirmed that sacubitril and valsartan can reduce heart failure and cardiovascular death The risk of waiting for a hard end point
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Due to multiple vascular bed diseases, stroke patients are often at a higher risk of cardiovascular events.
Sacubitril and valsartan can reduce such risks and ultimately benefit stroke patients
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In conclusion, sacubitril and valsartan can not only lower blood pressure effectively and lastingly, but also protect blood vessels and optimize the regulation of blood pressure in patients with different blood pressure levels.
It may further reduce the benefits of stroke events and recurrences, and is approved for hypertension.
After the indications, the clinical application of this drug is very worth looking forward to
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References: [1] Chinese Medical Association Neurology Branch, Chinese Medical Association Neurology Branch Cerebrovascular Disease Group.
Guidelines for the Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack in China 2014.
Chinese Journal of Neurology, 2015 , 48(4): 258-273.
[2] China Cardiovascular Health and Disease Report Writing Group.
Summary of China Cardiovascular Health and Disease Report 2019.
Chinese Journal of Circulation, 2020, 35(9): 833-854.
[3 ] Li Jing, Zhang Dan, Li Xi, et al.
Investigation on the current status of treatment of patients with ischemic stroke combined with hypertension.
Chinese Journal of Hypertension, 2011, 19(3): 246-250.
[4] China Cardiovascular Health and Disease Report Writing Group.
Summary of China Cardiovascular Health and Disease Report 2019.
Chinese Journal of Circulation, 2020, 35(9): 833-854.
[5]Huo Y, Li W, Webb R, et al.
Efficacy and safety of sacubitril /valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized, double-blind, 8-week study.
J Clin Hypertens (Greenwich).
2019, 21(1): 67-76.
[6]Wang JG, Yukisada K , Sibulo A Jr, et al.
Efficacy and safety of sacubitril/valsartan (LCZ696) add-on to amlodipine in Asian patients with systolic hypertension uncontrolled with amlodipine monotherapy.
J Hypertens.
2017, 35(4):877-885.
[7 ]Selvaraj S,J Am Coll Cardiol.
2020 Mar 11.
pii: S0735-1097(20)30518-0.
[8]Williams B, Cockcroft JR, Kario K, et al.
Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study.
Hypertension.
2017 Mar: 69(3): 411-420.
[9] Ruilope LM, Dukat A, Böhm M, et al.
Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study .
Lancet, 2010, 375(9722): 1255-66.
[10] Williams B, Cockcroft JR, Kario K, et al.
Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study.
Hypertension.
2017, 69(3): 411-420.
[11]Korshunov VA, Quinn B, Faiyaz A, et al.
Strain-selective efficacy of sacubitril/valsartan on carotid fibrosis in response to injury in two inbred mouse strains.
Br J Pharmacol, 2019, 176(15): 2795-2807.
[12]Zhang H, Liu G, Zhou W, et al .
Neprilysin Inhibitor-Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice.
Sci Rep.
2019, 24: 9 (1): 6509.
Expert profile Ge Junnan, Academician Ge Junbo , Academician of the Chinese Academy of Sciences, internationally renowned cardiovascular expert, Changjiang Scholars Distinguished Professor, winner of the National Outstanding Youth Fund
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The current director, professor and doctoral supervisor of the Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, the director of the Shanghai Institute of Cardiovascular Diseases, the director of the Shanghai Cardiovascular Clinical Medicine Center, the dean of the Institute of Biomedicine, Fudan University, and the Department of Cardiology, Chinese Medical Doctor Association President of the Physician Branch, the 10th Chairman of the Cardiovascular Branch of the Chinese Medical Association, the chairman of the Chinese Cardiovascular Health Alliance, the standing director of the World Heart Federation, the international consultant of the American College of Cardiology, the former chairman of the Asia-Pacific Society of Interventional Cardiology, the Bethune Medal, China Physician Award, Shulan Medicine Award and other winners
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Served as editor-in-chief of "Cardiology Plus", associate editor of "Herz", associate editor of "Chinese Journal of Cardiovascular Disease", and associate editor of "Chinese Journal of Interventional Cardiology"
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He has been committed to promoting the scientific theoretical innovation, clinical technology innovation and scientific research achievements transformation of cardiovascular diseases in China for a long time.
As the first complete person, he won the second prize of National Science and Technology Progress Award, the second prize of National Technology Invention Award, and the first prize of Shanghai Science and Technology Progress Award.
There are 14 science and technology awards, including the first prize of Shanghai Technology Invention Award and the first prize of Science and Technology Progress Award of the Ministry of Education
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Professor Dong Qiang is a leading talent in Shanghai and one of the top ten public health workers in Shanghai
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Director of the Department of Neurology, Huashan Hospital Affiliated to Fudan University, Deputy Director of the National Center for Neurological Diseases (Huashan), Deputy Chairman of the Chinese Medical Association Neurology Branch, Vice Chairman of the Chinese Stroke Society, Chairman of the Shanghai Medical Association Neurology Committee, Shanghai Chairman of the Neurologist Branch of the Municipal Medical Association, Director of the Shanghai Neurological Disease Clinical Medicine Center, Director of the Shanghai Neurology Quality Control Center, and Executive Vice President of the Shanghai Stroke Society
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