Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death and quality of life in the elderly. And as age increases, ASCVD prevalence and morbidity and mortality increase accordingly. Statins are safe and effective lipid-regulating drugs. In 2010, China issued the “Chinese Expert Consensus on the Use of Statins in the Elderly with Dyslipidemia”; in 2015, experts in the field of lipidology in China revised the guidelines based on the international guidelines on lipid management and clinical evidence published in recent years. In 2015, experts in the field of lipid management in China revised the guidelines based on the international guidelines and clinical evidence published in recent years.
I. Characteristics of dyslipidemia in the elderly
The epidemiological findings show that the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) gradually increase with age. Compared with European and American countries, the mean levels of TC, LDL-C and TG in elderly people in China are lower than those in western populations, with mild and moderate increases predominating.
II. Clinical evidence
Results from clinical trials and geriatric subgroups in the elderly show that statins significantly reduce the prevalence of cardiovascular disease, morbidity and mortality, and the incidence of cardiovascular and cerebrovascular events. However, there is a lack of data from clinical trials of statins designed for the prevention and treatment of cardiovascular disease in older adults over 80 years of age.
III. Treatment goals
The consensus recommends that before applying statins, the benefit-risk ratio of treatment should be fully weighed, and the target, type and dose of statin therapy for the elderly should be determined according to individual characteristics, and the target of lipid-regulating therapy is recommended
IV. Selection of drugs
The existing domestic statins include lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, resulvastatin and pitavastatin. Lovastatin, simvastatin, fluvastatin, atorvastatin and pitavastatin are lipophilic statins; pravastatin and resevastatin are hydrophilic statins. The main lipid-regulating ingredients of Lipocon capsules are lovastatin and statin congeners. 1.2 g of Lipocon capsules contains about 10 mg of lovastatin.
Lovastatin is more easily absorbed when taken with food, while Rosuvastatin, Simvastatin and Pitavastatin are not affected by food, and Atorvastatin, Fluvastatin and Pravastatin affect absorption when taken with food. The magnitude of cholesterol lowering varies by type and dose of statin.
Note: From the US Food and Drug Administration website (http ://www.fda.gov/Drugs/DrugSafety/ucm256581), based on individual statin, non-elderly efficacy data, statin non-direct efficacy comparison data;a high intensity: statin daily dose reduces LDL-C by ≥50%, moderate intensity: statin Daily dose of statins reduces LDL-C by 30%-50%, low intensity: daily dose of statins reduces LDL-C by <30%;b Lipocon 1.2 g/d reduces LDL-C by 28.5%.
V. Lipid monitoring
For those with lifestyle interventions: review lipid levels at 6-8 weeks, adhere to the intervention if the standard is met or significantly improved, and review after 3-6 months; if the standard is consistently met, review at 6-12 months.
Those who apply statin: pay attention to the presence of myalgia, muscle pressure, muscle weakness, fatigue and gastrointestinal symptoms. Before taking the drug and 4 weeks after taking the drug, review the blood lipids, liver enzymes, muscle enzymes and kidney function; if the standard is not reached in 3-6 months, adjust the dose or type of statin and review every 6-12 months after reaching the standard.
Discontinuation of statin: When the blood ALT and AST exceed 3 times the upper limit of normal or creatine kinase rises more than 5 times the upper limit of normal, the statin should be discontinued and rechecked until it returns to normal; if it does not return to normal, other causes should be excluded.
For those who have abnormal liver enzymes and muscle enzymes, the benefits and risks should be evaluated again before deciding whether to continue the application; if continued, change the type or reduce the dose and observe closely.
Safety of statins for the elderly
Generally, statins are safe and well tolerated by the elderly, so that the blind application of high-dose statins can avoid adverse reactions. Note that statins are contraindicated in patients with active liver disease, decompensated cirrhosis and acute liver failure, persistent elevation of unexplained liver enzymes and any cause for elevation of serum liver enzymes above 3 times the upper limit of normal.
Chronic liver disease is not a contraindication to statin use. However, statins can increase adverse effects when combined with anti-hepatitis viral drugs, and statins that are not metabolized by hepatic cytochrome P450 enzymes (CYP)3A4 should be selected.
People with renal insufficiency are prone to statin-related adverse reactions, so for people with impaired renal function (GFR <60 ml-min-1-1.73 m2), a dose that has been proven safe and effective in current clinical trials is recommended.
VII. Recommendations and precautions
1. All elderly patients with dyslipidemia are encouraged to adjust their diet and adopt a healthy lifestyle. The decision of how to reduce weight and exercise should be made according to the patient’s own situation, and it is not advocated that elderly people should control their diet too strictly and reduce their weight too quickly.
2. Lipid-regulating drugs should be selected according to the individual characteristics of elderly people. If there are no special reasons or contraindications, elderly people with multiple ASCVD risk factors should be encouraged to use statins. For elderly patients who cannot tolerate statins, consider: (1) changing different kinds of statins; (2) reducing the dose of statins; (3) taking small doses of statins on alternate days. For elderly people whose TC or LDL-C levels drop rapidly after using small doses of statins, attention should be paid to exclude whether they have wasting diseases such as tumors.
3. Statin-related adverse reactions in muscle, liver, kidney and new-onset diabetes mellitus increase with increasing statin doses. The use of statins in elderly ASCVD patients should be started at small or moderate doses and later adjusted according to statin efficacy to avoid statin adverse effects. Compared with patients <65 years of age, the same dose of statins can reduce LDL-C by 3%-4% more in elderly patients, and most elderly patients can achieve the lipid standard with medium or small doses of statins. For very high-risk patients such as ACS, medium-dose statins can be used to achieve the lipid standard as soon as possible. For elderly patients who cannot reach the target with medium-dose statins, they can be combined with ezetimibe. For elderly people with multiple cardiovascular disease risks, low-dose statins can be considered for primary prevention.
4. With aging, physiological changes in the elderly lead to muscle atrophy and muscle weakness, and the muscle adverse effects caused by statins can aggravate the related symptoms and affect the functional status and quality of life of the body. Some patients may experience adverse effects, such as muscle weakness, when they do not have elevated muscle enzymes or myopathy, which reduces quality of life and increases the likelihood of trauma from falls. Therefore, the benefits/risks of lipid-modifying therapy in the elderly should be fully evaluated before and after the use of statins to avoid the adverse effects of statins.
5. Elderly patients who are female, thin, combined with chronic renal insufficiency, perioperative, or have hypovolemia are at increased risk of myopathy and should be strictly controlled for indications and monitored for adverse effects. When statins are used for the prevention of ischemic cerebrovascular disease, elderly patients with poor blood pressure control, history of cerebral hemorrhage or high risk of cerebral hemorrhage need to weigh the risks and benefits before deciding whether to use them.
6. Physiological changes in the elderly lead to decreased liver and kidney function and frequent use of multiple drugs, and attention should be paid to drug interactions. Improper selection of combination drugs may increase the adverse effects of drugs or reduce the efficacy. Drugs with different metabolic pathways in the liver or in the body should be used as much as possible.
Age should not be an obstacle to the use of statins in elderly people (≥80 years old). The advantages and disadvantages of lipid-regulating therapy should be fully weighed according to the risk stratification of cardiovascular disease, combined with physiological age, liver and kidney function, concomitant diseases, combined medications, and life expectancy, and lipid-regulating drugs should be selected positively and prudently.
8. After using statins to achieve the lipid standard, long-term medication should be adhered to, and the dose can be adjusted or even replaced by different statins according to the lipid level. The increase of lipids or even rebound after discontinuing statins can significantly increase cardiovascular events and mortality.