Li Qing, TEDA Hospital, Tianjin University

On June 1, the State Food and Drug Administration (SFDA) issued a major news release, formally approving the sakubutravir valsartan produced by Novartis Pharmaceuticals, a Swiss pharmaceutical company, to be used in the treatment of high blood pressure. So far, antihypertensive drugs in the original six antihypertensive drugs has increased to the seventh, antihypertensive drugs family happy to add new members.

High blood pressure and diabetes are two of the most common chronic diseases, and two of the most dangerous to human life and health.

In the last two decades, insulin for diabetes has been updated many times, and new hypoglycemic agents such as DPP4 inhibitors (leptin), GLP-1 agonists (peptide), and SGLT2 inhibitors (leupeptin) have emerged, providing more choices for diabetes treatment.

In contrast, however, the development of antihypertensive drugs has been virtually stagnant. Since the launch of ARBs (sartans) 20 years ago, there have been no new varieties of antihypertensive drugs on the market, except for the addition of a few new ARBs such as olmesartan and memesartan. Aliskiren, a renin antagonist also manufactured by Novartis Pharmaceuticals, was not promoted after its launch for a number of reasons. The approval of sacubitril valsartan for the hypertension indication will usher in a new era in hypertension treatment.

Understanding sacubitril valsartan starts with understanding blood pressure and regulation of the cardiovascular system.

It is now known that there are three major neuroendocrine systems that play an important role in regulating normal blood pressure and cardiac and renal function: the sympathetic nervous system, the renin-angiotensin-aldosterone system (RAS) and the natriuretic peptide system.

Over-activation of the sympathetic nervous system and the RAS system for various reasons can cause vasoconstriction, increased heart rate, elevated blood pressure, sodium and water retention, heart failure, kidney failure, etc., which are all "destructive". After the activation of natriuretic peptide system, it can increase myocardial contraction, improve myocardial oxygen consumption, dilate blood vessels, reduce blood pressure, improve renal blood supply, diuretic, sodium excretion, etc., which brings "protective effect".

The activation of natriuretic peptide system can antagonize the harm brought by the over-activation of RAS system and the over-activation of sympathetic nervous system, which can be said that natriuretic peptide is the "natural protector" of cardiovascular system and kidney, and natriuretic peptide system is the "natural enemy" of RAS system and sympathetic nervous system. "

But it's not just the RAS and the sympathetic nervous system.

However, endogenous natriuretic peptide activity is short-lived, and some of it is degraded by enkephalinase. Therefore, the natriuretic peptide system is often at a disadvantage in the battle with the RAS and the sympathetic nervous system. If you can increase the activity of the natriuretic peptide system, you can treat heart failure, dilate blood vessels, lower blood pressure, diuretic swelling, improve renal blood supply.

Currently approved for the treatment of hypertension, antihypertensive drugs are divided into six categories:

A: ACEI (Prilosec antihypertensive drugs), ARB (sartan antihypertensive drugs), Alpha (alpha) receptor blockers (terazosin, etc.);

B: Beta (β) receptor blockers (lorzolol type antihypertensive drugs);

C: CCB (depressant drugs);

C: CCB (diphenhydramine). antihypertensives);

D: Diuretics (thiazide diuretics, thiazide-like diuretics, aldosterone antagonists).

Among them, prilosec, sartans antihypertensive agents and aldosterone antagonists control blood pressure by antagonizing the RAS system; alpha-blockers and beta-blockers control blood pressure by blocking the sympathetic nervous system; diphenhydramine antihypertensive agents control blood pressure by vasodilating the blood vessels; and diuretics lower blood pressure by sodium excretion.

Sacubitril valsartan breaks down into sacubitril and valsartan when it enters the body. Sacubitril can inhibit enkephalinase, so that the degradation of natriuretic peptide is reduced, and the natriuretic peptide system continues to remain active; and valsartan, as a sartan-type antihypertensive drug, in addition to lowering the effect of blood pressure, but also to avoid the enkephalinase is over-inhibition of the side effects brought about by the enkephalinase. The combination of the two components, complementary, pearl, can control heart failure, improve cardiac and renal blood supply, sodium diuresis, and have a clear and powerful antihypertensive effect.

Therefore, the approval of Sacubitril valsartan for hypertension is not only a new member of the antihypertensive drug "club", but more importantly, it is the beginning of a new era of hypertension treatment.

Sacubitril valsartan is produced by the world's second largest pharmaceutical company, Switzerland Novartis Pharmaceuticals, under the trade name of Nuoxintol.

Entering our country in July 2017, it was initially approved for the treatment of heart failure, which is a landmark drug in the history of heart failure treatment, and is now recommended by the world's major guides as a cornerstone drug in the treatment of heart failure, and other treatment programs for heart failure should be carried out on the basis of Sacubitril valsartan.

Subsequently, a large number of clinical studies have found that sacubitril valsartan also has a clear antihypertensive effect, and has a therapeutic effect on simple hypertension.

By the United States, Europe, Japan and other countries to carry out 13 large clinical studies meta found that Sacubitril valsartan 200mg per day, the average reduction in blood pressure is 18-20/8-10mmHg, basically equivalent to 2 tablets of other antihypertensive drugs to reduce blood pressure.

And Sacubitril valsartan on 24-hour blood pressure can be smooth control, better reduce the average blood pressure at night, salt-sensitive hypertension, refractory hypertension, hypertension combined with left ventricular hypertrophy, hypertension combined with chronic kidney disease and other serious hypertension effect is better, and lower urinary protein and renal protection effect. If used in combination with diphenhydramine antihypertensive drugs, the effect is better.

The biggest pitfalls in the clinical use of sartan-type antihypertensive drugs and Prilosec antihypertensive drugs is the elevation of blood potassium and blood creatinine, due to these two pitfalls, some patients with chronic kidney disease combined with hypertension are forced to give up the sartan-type antihypertensive drugs and Prilosec antihypertensive drugs that originally have a protective effect on the kidneys.

Sacubitril, on the other hand, can dilate the small glomerular entry arteries and balance the intraglomerular pressure. In addition to improving the blood supply to the kidneys, the side effects of elevated blood creatinine and elevated blood potassium are significantly reduced compared to those of sartan-type antihypertensives, and the safety is better.

The approval of sacubitril valsartan hypertension indication provides a new option for hypertension treatment, especially for hypertension combined with heart failure, hypertension combined with cardiovascular disease, hypertension combined with chronic kidney disease, refractory hypertension, etc., and provides a more effective "weapon".

All of the new drugs, there is a **** the same problem, that is, the price is slightly higher, I believe that with the implementation of band purchasing, the price will drop significantly. The former Wang Xie Tangqian Yan, will eventually fly into the common people's homes.

June 1 is Children's Day, perhaps coincidentally, Sacubitril valsartan hypertension indications approved on this day, as the antihypertensive drug family descended a new member, bringing new hope to the treatment of hypertension, and I believe that in the near future, this new member will grow into a pillar of the fight against hypertension.