For people with atherosclerosis, statins are commonly used drugs to prevent cerebral infarction and myocardial infarction. The main measure of whether the medication is effective in preventing the disease is whether the level of low-density lipoprotein cholesterol (LDL-C) is up to standard.
When using statins, why do doctors always use medium and low doses, and even if the LDL-C levels are not up to standard, they basically take them in combination with other medications, and rarely use high doses of statins?
I. The biggest risk of atherosclerosis is the rupture of hardened plaques, which leads to platelet aggregation and the formation of blood clots, resulting in cerebral infarction or myocardial infarction. Statin drugs can not only reduce blood lipids, but also anti-atherosclerosis, stabilize the plaque so that it is not easy to rupture, widely used in the world.
However, statins were not developed in China, so the samples taken for clinical trials were mainly European and American. When used in China, it is found that Chinese people are more sensitive to statins and can achieve better lipid-lowering effect with lower dose, but Chinese people also have lower tolerance to statins, and the probability of adverse reactions is greater at higher doses, so when statins are used in China, they are mainly used in medium and low doses, and rarely used in high doses.
II. The statin “plus 6 principle” in the use of statins, people found that, regardless of what kind of statin drugs, drug dose and efficacy is not an equal relationship. Taking the lowest dose of statins can produce a reduction in LDL-C levels of about 30% of the efficacy of the drug, but doubling the dose of the drug, the reduction in LDL-C levels, can only be increased by about 6%, that is, the “plus 6 principle”.
For example, if a person takes 10 mg of simvastatin and his LDL-C level is reduced by 30%, then he takes 20 mg of simvastatin and his LDL-C level is reduced by only 36%; he takes 40 mg of simvastatin and his LDL-C level is reduced by 42%.
And when the dose of the drug is doubled, the incidence of adverse effects increases significantly. So simply increasing the dose of a statin is not “cost-effective” in terms of benefit versus risk.
III. It can be used in conjunction with other lipid-lowering drugs In the use of statins, there are two key indicators of LDL-C levels. For people who have not had cerebral infarction, myocardial infarction, coronary heart disease and other cardiovascular diseases, the LDL-C level is controlled below 2.6mmol/L; for people who have had an attack of related diseases, the LDL-C level requires control below 1.8mmol/L.
There are many people who ask Huazi, statins have been used to a moderate dose, but the LDL-C level is not yet up to standard, continue to increase the dose and worry about adverse reactions, what should be done? Huazi said, this situation will usually take statins and other lipid-lowering drugs in combination to control LDL-C levels, rather than increase the dose.
The most commonly used regimen is a combination of a moderate-dose statin with the cholesterol absorption inhibitor ezetimibe. Ezetimibe can continue to reduce LDL-C levels by 20% to 30% on top of statins, generally without increasing adverse effects and with a good safety profile.
Combining statins with PCSK9 inhibitors can also be considered, but PCSK9 inhibitors are more expensive and more burdensome for patients.
What if the initial LDL-C value is too high and it is difficult to bring it down to the target value? Expert opinion nowadays is that as long as the LDL-C level can be reduced by 50%, it can also produce a better disease prevention effect, and it is not necessary to increase the dosage of the drug in order to pursue the goal of reaching the standard.
To summarize, because of the differences between Chinese and European and American races, the sensitivity and tolerance of statins are different, so China usually uses medium and low doses of statins, and seldom uses high doses of statins. Moreover, statins have the “plus 6 principle”, so in order to minimize the occurrence of adverse effects when the LDL-C level is not under control, most of them are used in combination with other lipid-lowering drugs, rather than increasing the dose alone.