October 4, 2022

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Can current treatments delay the onset of ASCVD to 100 years of age?

Can current treatments delay the onset of ASCVD to 100 years of age?



 

Can current treatments delay the onset of ASCVD to 100 years of age? Professor Eugene Braunwald: Can the onset of ASCVD be delayed to 100 years of age?

 

If you ask how long a person wants to live, I believe the vast majority of the answer will be “Longevity.” However, disease, especially atherosclerotic cardiovascular disease (ASCVD), is a huge stumbling block to the realization of this desire.

 

However, if there is such a treatment that only takes a few minutes of injection every year, it can delay ASCVD until after 100 years of age. Would you cruelly refuse it?

 

Recently, Professor Eugene Braunwald, a leader in the field of global cardiovascular disease research, published an article “How to live to 100 before developing clinical coronary artery disease: a suggestion” in the column of the European Society of Cardiology [1].

In his article, he proposed that LDL-C is the most important risk factor leading to atherosclerosis and plays a key role in the development of ASCVD. Therefore, the early and long-term effective control of LDL-C levels is expected to delay the onset of ASCVD by 30 years.

 

Perhaps you are a little strange to this name. Professor Eugene Braunwald not only served as a member of the National Academy of Sciences, but also awarded him the title of Distinguished Professor by Harvard Medical School. The American Heart Association also established the annual academic mentor award for him. Such outstanding achievements and contributions can reflect his academic status and influence in the industry.

 

So what exactly is Professor Eugene Braunwald’s coup on how to delay the onset of ASCVD for 30 years?

 

 

Although there is a dazzling array of lipid-lowering treatments, there are still difficulties

 

At present, there are a wide variety of drugs that lower LDL-C clinically, and statins are familiar to everyone. In recent years, PCSK9 inhibitors have been gaining momentum. PCSK9 is a preprotein mainly synthesized in the liver. By antagonizing the degradation of LDL receptors by PCSK9, it can increase the binding, uptake and utilization of LDL-C by the liver LDL receptors, which can be based on the effective lipid-lowering effects of statins. Further reduce the LDL-C level by more than 50%, significantly reduce the risk of cardiovascular events in patients, and the safety and tolerability are also very good.

 

However, lipid-lowering treatment does not mean “fishing for three days and drying the net for two days.” Long-term continuous treatment is necessary. Existing treatments seem to have no shortcomings, but they actually expose two important problems:

 

Trouble

PCSK9 inhibitors have a relatively short half-life, and patients need to be injected subcutaneously every 2 or 4 weeks. A few months or years may be able to persist, but long-term or even life-long treatment, compliance is difficult to guarantee;

 

Costly

Monoclonal antibody treatment is currently very expensive, and secondary prevention populations in many countries have not yet been covered by medical insurance. Primary prevention in asymptomatic people without ASCVD events does not have the validity of pharmacoeconomics.

 

 

The lipid-lowering principle of ASCVD: maintain low blood lipids as early as possible and for a long time

 

Professor Eugene Braunwald charted the relationship between LDL-C levels accumulated in the blood and age, and further visually revealed the relationship between the LDL-C threshold level and age in the onset of ASCVD (Figure 1) [1].

 

Can current treatments delay the onset of ASCVD to 100 years of age?
Figure 1 The relationship between the cumulative LDL-C threshold level of ASCVD and age

 

The green line A in the figure represents that in a natural state (or taking statins), the cumulative LDL-C will generally reach the threshold of cardiovascular events at the age of 70. The red B line represents untreated patients with familial heterozygous hypercholesterolemia. Their baseline LDL-C level averages 5.2 mmol/L, and they generally reach the threshold of cardiovascular events at the age of 35.

 

Professor Eugene Braunwald suggested that if ordinary people can inject 300 mg of Inclisiran (a new type of small interfering RNA (siRNA) drug) once a year at the age of 30, LDL-C can be effectively controlled and maintained at a low level for a long time. The threshold of cardiovascular events will also be delayed by 30 years, by which time we will all be a hundred years old. In addition, the delay of the onset threshold also depends on the initial age of our use of Inclisiran, that is, the earlier the better.

 

 

What is the sacred small interfering RNA Inclisiran?

 

“Inject once a year.” I believe that you, who are sharp-eyed and deeply aware of the current lipid-lowering predicament, must have not missed these keywords. Then what is the sacred Inclisiran of Professor Eugene Braunwald?

 

Inclisiran is the world’s first small-molecule interfering RNA (siRNA) drug for regulating blood lipids. It can specifically recognize and bind receptors on the surface of liver cells and enter liver cells, inhibit the translation and synthesis of PCSK9 protein, and block the degradation of LDL receptors, thereby promoting the recycling of LDL receptors and continuing to take up more LDL- C, thereby reducing the level of LDL-C in the blood.

 

Compared with other PCSK9 inhibitors, Inclisiran can be effective for up to about 300 days after a single administration. That is to say, for patients whose LDL-C level is higher than the disease threshold, only subcutaneous administration every 6 months is required. The maximum dose of statins can be achieved by injection, and the average reduction in LDL-C can reach more than 50% (Figure 3) [4,6,7]. For ordinary people, as Professor Eugene Braunwald mentioned, one injection (perhaps) a year in advance can effectively suppress the age of onset of ASCVD. Of course, this needs more clinical evidence to confirm.

 

Can current treatments delay the onset of ASCVD to 100 years of age? Can current treatments delay the onset of ASCVD to 100 years of age?
Figure 3 ORION-10 and ORION-11 research results

 

 


Summary

 

Well, after reading the method proposed by Professor Eugene Braunwald and the research results related to Inclisiran, I believe you are already shocked, right?

 

In the past, the pain of frequent medication/injection has plagued many patients with chronic diseases. However, with the development of medicine and the advancement of technology, the use of drugs has become more convenient, allowing patients not only to live long, but also to live well. The concept mentioned by Professor Eugene Braunwald in this article has undoubtedly refreshed our understanding of traditional lipid-lowering treatments. Inclisiran is expected to become a new weapon for people with high blood lipids to easily control LDL-C, allowing more people to achieve “long life.” 100 years old”!

 

 

(source:internet, reference only)


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