Hypertension is one of the most common chronic diseases, which is highly correlated with stroke, coronary heart disease, heart failure, atrial fibrillation and so on. It is one of the main inducing factors of various cardiovascular events, and cardiovascular disease death has become the first cause of death in China.
In October 2016, the CPC Central Committee and the State Council issued the "healthy China 2030" planning outline, which clearly implemented the comprehensive prevention and control strategy of chronic diseases. In July 2019, the State Council issued the "opinions on the implementation of the healthy China action" and put forward specific targets for the prevention and control of cardiovascular and cerebrovascular diseases: by 2022 and 2030, the mortality rate of cardiovascular and cerebrovascular diseases will be reduced to 209.7/100000 and below and 190.7/100000 and below respectively. In July of the same year, the "healthy China action (2019-2030)" issued by the healthy China action Promotion Committee further refined the specific objectives of hypertension management.
It can be said that to achieve the goal of "healthy China 2030", prevention should be the first and the front should be moved forward.
Hypertension management faces challenges
With the development of society, the acceleration of people's work pace, the pressure of life and competition, the change of lifestyle and habits, the incidence rate of hypertension will keep increasing in a long period.
Since 1958, six national surveys have shown that the prevalence of hypertension in China continues to rise, and the number of patients continues to increase. The results of the epidemiological survey on hypertension among Chinese adults (35-75 years old) in 2018 showed that there was 1 hypertension patient in every 5 Chinese adults, the total number of hypertension patients was 245 million, and the hypertension control rate was only 15.3%. According to the "China cardiovascular disease report (2018)", the prevalence of hypertension in residents aged 18 and above in China is 27.9%. The prevalence of hypertension increases significantly with age. The rate of hypertension patients aged 65 and above is more than 50%, and the trend of hypertension patients younger is increasingly significant. Therefore, the prevention and treatment of cardiovascular and cerebrovascular diseases should start with hypertension management.
It can be said that early detection, early diagnosis and early treatment of hypertension are very important to control blood pressure, improve symptoms, prevent complications and carry out scientific disease management. For patients with hypertension, once diagnosed, in addition to comprehensive lifestyle intervention, individualized treatment should be carried out according to risk factors, subclinical target organ damage and clinical diseases, and long-term antihypertensive drugs should be given priority.
At present, China is still facing the challenges of large number of patients with hypertension, low compliance rate, and poor management of special hypertension and complications. In addition to strengthening community service management, strengthening the research and development of new hypertension drugs is one of the ways to actively respond to the current challenges.
New strategies for drug research and development
According to the comprehensive risk assessment, non drug intervention and drug intervention are adopted in the treatment of hypertension. After decades of development, antihypertensive drugs include diuretics, beta blockers, calcium antagonists, angiotensin-converting enzyme inhibitors (pril), angiotensin receptor blockers (sartans), etc.
It is understood that a large number of antihypertensive drugs have been listed in the world, with traditional anti hypertension mechanism as the main mechanism. The peak period of research and development of conventional antihypertensive drugs was in the 1980s-1990s. In the past 20 years, 40 antihypertensive drugs were approved by the food and Drug Administration (FDA). However, before the 1980s, due to the accumulation of hypertension in basic medical research, this period was the storage period for the development of antihypertensive drugs.
Some people in the industry said that the research and development trend of new antihypertensive drugs in the future should conform to the clinical value and meet the clinical needs of achieving strong blood pressure reduction, target organ protection, complication management and treatment of special types of hypertension.
Although the current research on antihypertensive drugs has entered a slow down stage, in order to meet the clinical needs, the treatment targets for hypertension still belong to the research focus. In recent years, the research and development of antihypertensive drugs such as aldosterone related inhibitors, aminopeptidase inhibitors, ACE2 / ang (1-7) / MAS receptor axis agonists, vasopeptidase modulators and other antihypertensive drugs have made great progress, but most of them are still in the research and development stage, and there is still a long way to go before they are put on the market. Among them, angiotensin receptor enkephalin inhibitor (Arni) has been put on the market.
Arni was first used in the treatment of heart failure. As the first Arni drug in the world, sacubatravalsartan sodium tablet is a supramolecular compound of coerystal of enkephalin inhibitor sacubatro and angiotensin receptor antagonist valsartan.
In 2015, sakubatravalsartan sodium tablets were approved for marketing in the United States and the European Union. In 2017, China's drug regulatory authorities approved the product for adult patients with chronic heart failure with reduced ejection fraction.
It is reported that enkephalin is an endopeptidase, which can degrade a variety of endogenous peptides with vasodilation and cause vasoconstriction. Enkephalin inhibitors can effectively inhibit the activity of enkephalin and play an anti hypertension effect.
Li Yong, director of the cardiovascular research unit of Huashan Hospital Affiliated to Fudan University, said that hypertension patients need to reduce the incidence rate of coronary heart disease, left ventricular hypertrophy and heart failure while lowering blood pressure, which means that the strategies for choosing antihypertensive drugs are different.
The traditional treatment of hypertensive heart failure mainly adopts the "Golden Triangle" scheme composed of angiotensin-converting enzyme inhibitor (ACEI) / angiotensin receptor blocker (ARB) and other drugs. According to ish2020 international hypertension practice guidelines, Arni can replace ACEI or ARB for the treatment of systolic heart failure (hf-ref) in hypertensive population. The same treatment strategy is also applicable to patients with diastolic heart failure (HFPEF).
"Compared with the known effective full-dose ACEI regimen, Arni regimen can significantly reduce all-cause mortality on the basis of significantly reducing the hospitalization rate and cardiovascular mortality rate of patients with heart failure, which has made great progress in the field of heart failure treatment." Li Yong pointed out that "Arni can effectively reduce blood pressure in patients with hypertension, hypertension complicated with left ventricular hypertrophy, hypertension with coronary heart disease, and even hypertension with heart failure, and can also provide strong target organ protection."
New choice for patients with hypertension
Studies have shown that in addition to the treatment of heart failure, Arni has a certain therapeutic effect on hypertension. Data show that from 2010 to 2019, there are 13 Arni studies in the field of hypertension. The clinical trials of 6432 patients with different races and types of hypertension from Asian countries and regions including China, Europe and the United States and other countries and regions showed that the 24-hour antihypertensive effect of Arni was stable, safe and well tolerated.
"Long before the success in the field of heart failure, it was found that sakubatravalsartan can also effectively lower blood pressure," Li said. Its outstanding performance lies in the reversal of cardiac remodeling, which greatly delays the process of heart failure, thus avoiding the death caused by heart failure
"As a drug for the treatment of heart failure, Arni actually has a strong antihypertensive effect. It can effectively control 24-hour ambulatory blood pressure in patients with hypertension. It can be used as one of the long-term antihypertensive drugs to improve the blood pressure compliance rate of patients with hypertension." Wang Jiguang, director of hypertension Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University Medical School, said.
Studies have shown that sac can improve cardiac remodeling and enhance the vasodilatation, sodium, diuretic and sympathetic nervous system effects induced by natriuretic peptide system. Valsartan can antagonize the renin angiotensin aldosterone system (RAAS * system), thereby reducing the adverse effects of vasoconstriction, sympathetic nervous system excitation and water sodium retention. Therefore, it can help patients with hypertension and heart failure to "relax and reduce blood pressure" and multiple benefits.
Experts in the industry are looking forward to the application of sakubatravalsartan in the treatment of hypertension. "In recent ten years, there are few new drugs on the market in the field of hypertension treatment, and there is a strong desire for drugs with better antihypertensive efficacy, higher safety and good target organ protection." Professor Sun Ningling of Peking University People's Hospital said that we expect the clinical application value of Arni drugs in the treatment of patients with hypertension.
Based on the results of existing clinical trials, Wang Jiguang said: "sarkubatrovalsartan has the dual advantages of compound drugs, which can not only effectively treat heart failure, but also steadily reduce blood pressure. In the future, if Arni enters the field of hypertension, it can improve the treatment and management of hypertension to a certain extent. "
In the future, if Arni enters the field of hypertension, it can improve the treatment and management of hypertension to a certain extent. "
"Clinically, the ultimate effect of antihypertensive drugs should be converted into the reduction rate of cardiovascular death and all-cause death, which is the ultimate goal of clinical treatment of hypertension." Li Yong also looks forward to the future performance of sakubatravalsartan in the treatment of hypertension.
