Break through the traditional treatment!

Recently, a unique dual-channel multi-target mechanism of innovative drug sacubitril valsartan (Noxinto®) was approved for the treatment of essential hypertension, breaking the field of hypertension treatment for more than ten years The dilemma of no new drugs
.

In December 2021, sacubitril and valsartan were officially included in the National Medical Insurance List and officially opened at the beginning of the new year (January 1, 2022) (Table 1), which brings new opportunities for stroke patients with hypertension Choice and hope
.

Table 1 "National Basic Medical Insurance, Work Injury Insurance and Maternity Insurance Drug List (2021)" During the agreement period, China's stroke incidence rate in the negotiated drug section ranked first in the world, and it was the third leading cause of death after malignant tumors and heart disease1
.

According to statistics, there are about 11.
1 million people suffering from stroke in China, and about 1.
57 million people die from stroke every year.
2 The high incidence, disability, and death rate of stroke have caused tremendous mental pressure on individuals, families and the entire society.
And financial burden
.

Hypertension is the most important risk factor for stroke.
As many as 84.
2% of stroke patients have hypertension3, and the higher the blood pressure, the higher the risk of stroke4
.

Therefore, maintaining blood pressure stability is an important way to improve and delay the occurrence of stroke, but the current control rate of traditional antihypertensive drugs for stroke combined with hypertension is still not ideal
.

Sacubitril and Valsartan is the world’s first angiotensin receptor enkephalinase inhibitor (ARNI), a new single co-crystal composed of sacubitril and valsartan in a ratio of 1:1.
It can guarantee the full effect of the two main ingredients
.

Compared with traditional antihypertensive drugs, sacubitril and valsartan have a more comprehensive antihypertensive mechanism.
It uses the previously neglected new target of antihypertensive therapy-the natriuretic peptide system, through renal mechanism, vascular mechanism, and neurological mechanism.
A variety of endocrine pathways can achieve 24-hour stable blood pressure control, potent blood pressure reduction and multi-target organ protection, and reduce the risk of stroke and recurrence
.

Here, Yimaitong was fortunate to invite Professor Dong Qiang from Huashan Hospital Affiliated to Fudan University, Professor Xu Anding from the First Affiliated Hospital of Jinan University, and Professor Zhao Xingquan from Beijing Tiantan Hospital Affiliated to Capital Medical University, to focus on ARNI's whole-process management of reducing blood pressure in stroke patients.
A series of discussions
.

0124 hours of steady pressure control Professor Dong Qiang: The blood pressure management of stroke patients is a very important quality control goal
.

According to statistics, about 70% of patients with acute ischemic stroke (AIS) have elevated blood pressure, and blood pressure fluctuations in the acute phase also increase
.

Individual blood pressure variability (BPV) in the acute phase of AIS can affect the risk of stroke or recurrence in the future
.

Reducing blood pressure fluctuations during hospitalization and discharge follow-up may have a more important effect than the reduction of blood pressure
.

Therefore, for the management of BPV in AIS patients, antihypertensive therapy must not only meet the standard, but also long-term and stable pressure control to reduce blood pressure fluctuations
.

For example, drugs that can work within 24 hours have better blood pressure management effects than single short-acting drugs
.

The unique molecular structure and mechanism of sacubitril and valsartan make it capable of long-term and stable pressure control, even stronger than other drugs
.

The results of PARAMETER study 5 showed that sacubitril and valsartan treatment for 12 weeks can significantly reduce the 24-hour average brachial and aortic systolic blood pressure (SBP), which is better than angiotensin receptor antagonist (ARB), especially night blood pressure The decrease is more obvious (Figure 1)
.

Fig.
1 Sacubitril and valsartan treatment for 12 weeks, the peripheral and central 24-hour average dynamic SBP02 potent antihypertensive Professor Xu Anding: There is a very clear relationship between hypertension and stroke, and multiple studies have confirmed that antihypertensive treatment can be effective Significantly reduce the occurrence of stroke
.

For stroke patients, the reduction in blood pressure is more important to reduce the risk of stroke than the type of medication
.

At present, the control rate of hypertension in stroke patients is only 17.
6%6, and the lack of potent antihypertensive drugs is one of its important influencing factors
.

The multiple antihypertensive mechanisms of sacubitril and valsartan make it exert a better antihypertensive effect
.

Traditional antihypertensive drugs can only achieve a 50% reduction in blood pressure in 1 week, and about 75% in 2 weeks7, while sacubitril and valsartan can obtain 80% of the maximum blood pressure reduction in 1 week.
Treatment 2 The week is as high as 91%8
.

A randomized controlled trial (RCT) 9 in an Asian population confirmed that sacubitril and valsartan further reduced systolic blood pressure (SBP) compared with olmesartan.
From baseline to week 8, 200 mg sacubitril and valsartan reduced the average The sitting systolic blood pressure (msSBP) was 20.
48mmHg, and the same dose of Olmesartan was used to reduce 18.
15mmHg (Figure 2)
.

All this means that sacubatril and valsartan have a stronger antihypertensive ability
.

Figure 2 The average change of msSBP and msDBP in each treatment group from baseline to week 8.
03 Target organ protection Prof.
Zhao Xingquan: Patients with ischemic stroke are often accompanied by chronic diseases such as diabetes, chronic kidney disease, and coronary heart disease.
These diseases interact with each other.
The influence, mutual cause and effect, aggravated the damage to target organs such as the kidney
.

Sacubitril and Valsartan has a unique dual-channel multi-target mechanism of action.
In addition to its full antihypertensive effect, it also has the effects of multi-target organ protection and improvement of metabolic disorders
.

A number of clinical studies have confirmed that sacubitril and valsartan can significantly reduce hemoglobin (HbA1c) levels in patients with type 2 diabetes with reduced ejection fraction (HFrEF) and type 2 diabetes, and increase abdominal fat mobilization in obese patients with hypertension11 ( Figure 3); Improve glomerular filtration rate (eGFR) and delay the progression of kidney disease 12; Rapidly and continuously improve cardiac remodeling in patients with heart failure 13,14 (Figure 4); Protect the heart and reduce acute ischemic stroke 15, 16, and other cardiac complications in patients
.

The arrival of sacubitril and valsartan has brought a new breakthrough in the treatment of essential hypertension and hypertension comorbidities, providing better choices for patients with different conditions
.

Figure 3 Post-mortem analysis of the PARADIGM-HF study: ARNI treatment significantly reduced the average HbA1c (left); a metabolic profile study: ARNI treatment for 8 weeks significantly increased the catabolism of abdominal adipose tissue (right) Figure 4 PARADIGM-HF study: ARNI treatment was significant Delay the decline of eGFR by 23.
5% (left); EVALUATE-HF study: ARNI treatment has a rapid onset of 3 months (right).
It has been confirmed that it has been recommended by many guidelines.
It is clearly stated in the "Shanghai Expert Recommendations for the Management of Blood Pressure Variability in Inpatients with Ischemic Stroke" led by the Shanghai Stroke Society and led by Professor Dong Qiang from Huashan Hospital Affiliated to Fudan University: Shaku Baltrovalsartan has the effects of multi-target organ protection and improvement of metabolic disorders.
It also has unique advantages in reducing nocturnal hypertension and reducing BPV in Asian patients; it is recommended to use sand in the secondary prevention of patients with ischemic stroke and hypertension.
Cobatril and Valsartan
.

Secondly, the antihypertensive treatment of sacubitril and valsartan has also obtained the "2019 Asian Ambulatory Blood Pressure Monitoring Expert Consensus", "2020 Chinese Ambulatory Blood Pressure Monitoring Guidelines" and the "Sacubatril and Valsartan in Patients with Hypertension" published in 2021.
Approval and recommendation of relevant hypertension guidelines such as "Applying Chinese Expert Recommendations"
.

In summary, the proportion of stroke patients with hypertension in China is large, and traditional antihypertensive treatments are still insufficient
.

The natriuretic peptide system, which has been neglected in the past, has become a new target for antihypertensive therapy, allowing sacubitril and valsartan to break through the traditional mechanism and achieve better antihypertensive efficacy while exerting multi-target organ protection
.

Sacubitril and Valsartan was approved for primary hypertension indications and will be included in the National Medical Insurance List in the short term, which will benefit more stroke patients with hypertension and better help China's stroke prevention and treatment
.

This is bound to be the strongest "joy" sound made in the excellent "A" era! The MCC number EN621121882 is valid for 2022-12-30, and the data is expired and deemed invalid
.

Expert profile Professor Dong Qiang, Chief Physician, Doctoral Supervisor, Shanghai Leading Talent, Shanghai Top Ten Public Health Worker, Director of Neurology, Huashan Hospital Affiliated to Fudan University, Deputy Director, National Center for Neurological Diseases (Huashan), Deputy Director, Chinese Medical Association Neurology Branch , Vice President of the Chinese Stroke Association, Chairman of the Neurology Committee of the Shanghai Medical Association, Chairman of the Neurologist Branch of the Shanghai Medical Doctor Association, Director of the Shanghai Neurological Disease Clinical Medicine Center, and Director of the Shanghai Neurology Quality Control Center Shanghai Stroke Society Executive Vice President Professor Xu Anding Second Class Professor/Chief Physician, Doctoral Supervisor, Deputy Director of the Medical Department of Jinan University, Dean of the First Affiliated Hospital of Jinan University/Dean of the First Clinical Medical College of Jinan University, Director of the Cerebrovascular Disease Center of the First Affiliated Hospital of Jinan University, Guangdong Province Medicine Leading Talent, Vice President of the Chinese Stroke Society, Member of the Neurology Branch of the Chinese Medical Association and Deputy Group Leader of the Cerebrovascular Disease Group, Chairman of the Guangdong Provincial Stroke Society, Vice President of the Guangdong Provincial Hospital Association and Director of the Neurologist Branch, Deputy "Stroke & Vascular Neurology" The editor-in-chief executive director of the Guangdong Medical Association, the deputy chairman of the Neurology Branch, has been responsible for more than 30 projects such as the National Natural Science Foundation and other provincial and ministerial funds in the past ten years, with a total fund of more than 12 million yuan
.

Editor-in-chief, associate editor, and co-editor of 6 monographs, participated in the compilation of 2 undergraduate textbooks and published more than 200 papers, including more than 60 SCI papers
.

Many national and international conference academic committee members and invited academic lecture experts
.

Participated in the formulation of China's cerebrovascular disease guidelines and series of expert consensus, and presided over several expert consensus/guidelines writing Professor Zhao Xingquan, MD, chief physician, professor, and doctoral supervisor Director of the Department of Vascular Neurology, Member and Secretary-General of the Committee of Neurology Branch of the Chinese Medical Association; Deputy Chairman of the Neurology Branch of the Beijing Medical Association; Chairman of the Vertigo Professional Committee of the Neurology Branch of the Chinese Medical Doctor Association Chairman of the Stroke and Vertigo Branch of the Chinese Stroke Society National Health The Chairman of the Hemorrhagic Stroke Internal Medicine Professional Committee of the Family Planning Commission’s Stroke Prevention and Treatment Committee Secretary General of the Beijing Cerebrovascular Disease Prevention and Treatment Association won 2 second prizes for National Science and Technology Progress, 7 provincial and ministerial-level scientific and technological progress, and was selected into the "National Hundred, Thousand, Thousand, Thousand Talents Program" ", won the honorary title of "Young and Middle-aged Experts with Outstanding Contributions" by the Ministry of Human Resources and Social Security, and enjoy the special allowance of the State Council
.

References: 1.
Li X, et al, Annual data set on national mortality surveillance 2018.
Beijing: China Science and Technology Press, 2019.
2.
Wang W, et al, Prvalence, Incidence,and Mortality of Stroke in China: Results from a Nationawide Population-Based Survey of 480 687 Adults[J], Circulation, 2017,135:759-759.
3.
YJ Wang, et al.
China Stroke Statistics 2019: A Report From the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations.
Stroke and Vasclar Neurology.
2020,5( 3):211-239.
4.
Lacey B, et al.
Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study[J].
The Lancet.
Global health.
2018 Jun;6(6):e641-e649.
5.
Williams B, et al.
Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study[J].
Hypertension.
2017 Mar;69(3):411-420.
6.
Qinqin Cao, et al.
Hypertension unawareness among Chinese patients with first-ever stroke[J].
BMC Public Health, 2016 Feb 19;16(1):170.
7.
Lasserson DS, Buclin T, Glasziou P.
How quickly should we titrate antihypertensive medication? Systematic review modelling blood pressure response from trial data[J].
Heart (British Cardiac Society), 2011, 97(21): 1771-1775.
8.
Kario K, Tamaki Y, Okino N, Gotou H, Zhu M, Zhang J.
LCZ696,a First-in-Class Angiotensin Receptor-Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension [J].
Journal of clinical hypertension (Greenwich, Conn), 2016, 18(4): 308-314.
9.
Huo Y, 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].
Journal of clinical hypertension (Greenwich, Conn.
).
2019 Jan;21( 1):67-76.
10.
Seferovic JP, et al.
Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial[J].
Lancet Diabetes Endocrinol, 2017,5(5):333-340.
11.
J Jordan, et al.
Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension[J].
Clin Pharmacol Ther, 2017,101(2):254-263.
12.
Kevin Damman, et al.
Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure[J].
JACC Heart Fail, 2018,6(6):489 -498.
13.
Desai AS, et al.
JAMA, 2019, Sep 2;322(11):1-10.
14.
Januzzi JL, et al.
JAMA, 2019, Sep 2;322(11):1-1115.
Wira CR, et al.
Cardiac complications in acute ischemic stroke[J].
West J Emerg Med,2011,12(4):414-420.
16.
Burkot J, et al.
Decompensated heart failure is a strong independent predictor of functional outcome after ischemic stroke[ J].
J Card Fail, 2015, 21:642–646.
Sep 2;322(11):1-1115.
Wira CR, et al.
Cardiac complications in acute ischemic stroke[J].
West J Emerg Med,2011,12(4):414-420.
16.
Burkot J, et al.
Decompensated heart failure is a strong independent predictor of functional outcome after ischemic stroke[J].
J Card Fail,2015,21:642–646.
Sep 2;322(11):1-1115.
Wira CR, et al.
Cardiac complications in acute ischemic stroke[J].
West J Emerg Med,2011,12(4):414-420.
16.
Burkot J, et al.
Decompensated heart failure is a strong independent predictor of functional outcome after ischemic stroke[J].
J Card Fail,2015,21:642–646.