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    Home > Active Ingredient News > Study of Nervous System > ARNI optimizes the management of stroke and hypertension, and overcomes the barrier-free blood pressure at night!

    ARNI optimizes the management of stroke and hypertension, and overcomes the barrier-free blood pressure at night!

    • Last Update: 2021-06-17
    • Source: Internet
    • Author: User
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    *For medical professionals' reference only, sacubitril and valsartan are officially approved for hypertension indications, bringing new expectations for the treatment of stroke patients with hypertension! The stroke population is huge, and blood pressure at night cannot be ignored! Investigations show that stroke has become the first cause of death in China and the leading cause of disability in Chinese adults [1]
    .

    Hypertension is a high risk factor for stroke
    .

    Epidemiological surveys show that the incidence of hypertension in stroke population in China is as high as 74%, and every 10mmHg increase in systolic blood pressure (SBP) in Asian populations increases the risk of stroke by 53% [2]
    .

    Therefore, antihypertensive treatment is particularly important to prevent stroke
    .

    More seriously, compared with daytime blood pressure, night blood pressure is more closely related to the risk of death from all causes and cardiovascular and cerebrovascular diseases
    .

    IDACO research proved that the night blood pressure increased by 20mmHg, the risk of stroke increased by 36%, and the risk of cardiovascular death increased by 17% [3]
    .

    In addition, data from a J-HOP night blood pressure study showed that family SBP at night increased by 10 mmHg, and the risk of cardiovascular events (CVE) increased by 20% [4]
    .

    It can be seen that it is urgent to strengthen night blood pressure management
    .

    However, in the face of such a large population of stroke in China, the current clinically used drugs are not enough.
    The overall blood pressure compliance rate is only 15.
    3%, and the night blood pressure control is not ideal
    .

    So is there a drug that can more effectively manage blood pressure? Today we invited Professor Du Yifeng, director of the Department of Neurology of Shandong Provincial Hospital, to talk with us about a new type of antihypertensive drug, angiotensin receptor enkephalinase inhibitor (ARNI), which was officially approved for hypertension indications on June 1.
    )-What kind of beneficial effects can sacubatril and valsartan play! ARNI has an advantage in controlling blood pressure at night! The antihypertensive advantages of sacubitril and valsartan are mainly reflected in three aspects: powerful antihypertensive, intelligent antihypertensive and 24-hour lasting antihypertensive
    .

    A study of Asian patients with mild to moderate hypertension found that sacubatril and valsartan can further reduce SBP compared with olmesartan, with a maximum blood pressure reduction of 21.
    67mmHg[5]
    .

    This fully reflects the powerful hypotensive ability of sacubitril and valsartan
    .

    Figure 1 Sacubitril and valsartan can effectively reduce blood pressure and sacubitril and valsartan can also achieve "smart" blood pressure reduction
    .

    A study found that in patients with high baseline blood pressure (≥140mmHg), sacubitril and valsartan can significantly reduce blood pressure, while in patients with low baseline blood pressure (<120mmHg) it can keep blood pressure stable Level [6]
    .

    Figure 2 Sacubitril and Valsartan can intelligently lower blood pressure.
    In addition, an analysis of a total of 6064 hypertensive patients included in 12 studies showed that compared with angiotensin II receptor antagonist (ARB), Sacubitril and valsartan significantly reduced the patient's 24h ambulatory blood pressure [7]
    .

    Figure 3 Sacubitril and valsartan can reduce 24-hour ambulatory blood pressure, while sacubitril and valsartan have the same dazzling performance in improving night blood pressure
    .

    Effectively improve night ambulatory blood pressure: The first ARNI clinical study in Asian hypertensive patients included 481 hypertensive patients randomized treatment and ambulatory blood pressure monitoring.
    The results found that ARNI can effectively reduce dynamic blood pressure after 8 weeks of treatment The night dynamic SBP of blood pressure monitoring (ABPM), up to 16.
    14mmHg[8]
    .

    Figure 4 ARNI can effectively reduce nighttime ABPM and powerfully reduce nighttime average blood pressure: a randomized, double-blind, placebo-controlled, active-controlled study involving 1328 patients showed that compared with valsartan, the average number of patients after ARNI treatment The seated systolic blood pressure (msSBP) is reduced more significantly, and the maximum can be reduced by 9.
    01mmHg [9]
    .

    This proves that compared with ARB, ARNI has a stronger reduction in mean blood pressure at night
    .

    Figure 5 ARNI is stronger than valsartan in lowering the mean blood pressure at night, and the mean ambulatory blood pressure at night is better controlled: a randomized controlled trial found that at 12 weeks of treatment, compared with olmesartan, it reduced the mean dynamic systolic blood pressure (MASBP) by 9.
    1mmHg , Average dynamic central arterial systolic pressure (MACASP) 8.
    7mmHg, ARNI can further reduce MASBP up to 4.
    1mmHg and MACASP up to 3.
    4mmHg on this basis
    .

    Among them, the night segment (10:00pm-6:00am) has a greater decline.
    Compared with Olmesartan, ARNI can further reduce the night segment MASBP by 5.
    9mmHg and MACASP by 5.
    2mmHg[10]
    .

    Figure 6 ARNI is more effective than olmesartan in reducing night MASBP and MACASP.
    There are currently 13 research documents confirming the efficacy of sacubitril and valsartan in hypertension, including essential hypertension and salt sensitivity Hypertension and moderate to severe renal insufficiency combined with hypertension and other different types of hypertensive diseases
    .

    Based on the current evidence-based evidence, sacubitril and valsartan have been recommended by many authoritative guidelines and consensus.
    The "2020 Chinese Ambulatory Blood Pressure Monitoring Guidelines" pointed out that "it is recommended to use long-acting drugs alone or in combination to control daytime combined Nocturnal hypertension, or use new antihypertensive drugs that can effectively lower night blood pressure, such as sacubitril and valsartan"
    .

    In addition, ARNI can not only effectively reduce night blood pressure, but also can resist vascular fibrosis and arteriosclerosis, improve carotid plaque, and exert a powerful protective effect on cardiovascular and cerebrovascular
    .

    A retrospective analysis of 404 patients with essential hypertension found that the incidence of carotid plaque in stroke patients was 66.
    7%, which was much higher than the 55.
    2% in non-stroke patients [11]
    .

    In a study that used sacubitril and valsartan to treat apolipoprotein E-deficient mice, it was found that after 12 weeks of treatment, compared with valsartan, sacubitril Valsartan can significantly reduce plaque lipids, increase the thickness of the fibrous cap, stabilize the plaque, inhibit the process of arteriosclerosis, and reduce the formation of plaque [12]
    .

    Figure 7 Sacubitril and Valsartan can effectively improve carotid plaque.
    Why can ARNI have such excellent performance in reducing night blood pressure and cardio-cerebral vascular protection? Let us explore her unique mechanism of reducing blood pressure at night
    .

    What are the characteristics of ARNI with the new blood pressure reduction mechanism? The antihypertensive mechanism of the five traditional antihypertensive drugs is to inhibit the booster system, ignoring the natriuretic peptide system that focuses on lowering blood pressure
    .

    In the past, there have been studies on natriuretic peptides, and it was found that natriuretic peptides can benefit patients with hypertension through renal mechanism, vascular mechanism and neuroendocrine mechanism, but for many years, no long-acting oral drugs can intervene, only intravenous short-acting drips.
    Injecting drugs, chronic hypertension patients who have been taking drugs for a long time cannot use it, and the birth of sacubatril and valsartan will undoubtedly bring new gospel to hypertensive patients
    .

    In a study that included 118 elderly patients with asymptomatic hypertension, it was found that in hypertensive patients, the relationship between atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and 24-hour blood pressure levels was more than that of office blood pressure.
    The level is more closely related (P<0.
    001), so it is believed that natriuretic peptide may be an endogenous hormone that truly reflects the changes in blood pressure in 24 hours [13]
    .

    Figure 8 ANP and BNP levels are closely related to the 24-hour blood pressure level.
    ARNI makes full use of the previously neglected new target for lowering blood pressure-the natriuretic peptide system, which has a unique dual-channel multi-target mechanism of action, which can simultaneously act on The Renin-Angiotensin-Aldosterone System (RAAS) and Natriuretic Peptide System can inhibit the blood pressure mechanism while enhancing the blood pressure mechanism
    .

    On the one hand, sacubitril can produce desethyl sacubitril (LBQ657) under the catalysis of esterase.
    LBQ657 has the function of inhibiting enkephalinase activity and can increase the level of natriuretic peptides in the body.
    On the other hand, valsartan can inhibit RAAS, the two work together, and then play a role in lowering blood pressure and organ protection
    .

    Figure 9 Summary of the unique hypotensive mechanism of sacubitril and valsartan For stroke patients with hypertension, sacubitril and valsartan has a unique hypotensive mechanism and is currently the only long-acting natriuretic peptide Compared with traditional treatments, systemic drugs can further reduce 24h ambulatory blood pressure and night blood pressure, and have excellent cardio-cerebral protection, help stabilize carotid plaques, thereby reducing the risk of stroke occurrence and recurrence in patients
    .

    On June 1, sacubitril and valsartan was officially approved for hypertension indications in China.
    The clinical application of this drug in stroke patients with hypertension is very worth looking forward to
    .

    Expert profile Professor Du Yifeng • Director of the Department of Neurology and Doctoral Supervisor of Shandong First Medical University • Director of the Department of Neurology, Shandong Provincial Hospital and second-level chief physician • Director of Shandong Provincial Neurological Disease Clinical Medicine Research Center • Chief Scientist of the National Key Research and Development Program, Taishan Scholar Distinguished Expert•Vice President of Neurology Branch of Chinese Medical Doctor Association•Deputy Group Leader of Dementia and Cognitive Disorders Group of Neurology Branch of Chinese Medical Association•Deputy Editor-in-Chief of "Chinese Journal of Behavioral Medicine and Brain Science" Key research and development programs, key international cooperation projects of the National Natural Science Foundation of China, and general projects of the National Natural Science Foundation of China.
    More than 200 academic papers have been published in journals such as Nature Communications, AMA Neurology, Lancet Public Health, etc.
    References: [1] Cardio-Cerebrovasc Dis Prev Treat,October 2020,Vol.
    20,No.
    5[2]Lancet.
    2010 Jul 10;376(9735):112-123;[3]JAMA 2019; 322(5): 409-420.
    [4]Hypertension.
    2019 Jun;73(6):1240-1248.
    [5]Huo Y, et al.
    J Clin Hypertens (Greenwich).
    2019 Jan;21(1):67-76.
    [6]Selvaraj S ,J Am Coll Cardiol.
    2020 Mar 11.
    pii: S0735-1097(20)30518-0.
    [7]Cardiology.
    2020;145(9):589-598.
    [8]Kazuomi Kario, Hypertension.
    2014;63: 698-705; originally published online January 20, 2014;[9]Lancet.
    2010 Apr 10;375(9722):1255-66.
    [10]Williams B, et al.
    Hypertension.
    2017 Mar;69(3):411 -420.
    [11] Yao Yuexian, et al.
    Chinese Journal of Hypertension.
    2011,19(10)951-954.
    [12]Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination therapy (Sacubitril/valsartan) Supp resses AtheroscleroticPlaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice, (2019) 9:6509[13]J Hypertens .
    1998 Sep;16(9):1253-9.
    *This article is only used to provide scientific information to medical and health professionals and does not represent the platform's views
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