Intolerance to taking statin medications to lower cholesterol is a relatively common condition
Statins are considered “first-line medications” for treating high cholesterol. But at the same time, it leads to some patients becoming intolerant of continuing to take statin medications, which is a relatively common condition.
This condition represents one of the thorny medical problems that still needs to be understood by the medical community, which also still needs specific clinical methods to diagnose its presence and deal with it in the patient. It also needs patients to be alerted to the “signs” of its appearance and clarity in how they deal with it.
Health problem
In a sequential narrative, here is a presentation of this health problem in 8 points…
1. Coronary artery disease is still the leading cause of death in the world. With the current “obesity epidemic” and the growth of Metabolic Syndrome (a metabolic syndrome in which high blood pressure, high blood sugar, excess body fat around the middle, and abnormal levels of cholesterol or triglycerides), it is likely to continue to spread in the world. Height.
Along with high blood pressure, diabetes, and smoking, it has been consistently proven that high cholesterol and blood fats (hyperlipidemia) are one of the most important risk factors for the emergence and development of coronary artery disease, but at the same time they have a high potential to mitigate its damage. This makes it a “modifiable risk factor.”
Therefore, cholesterol-lowering therapy is important in achieving secondary (advanced) prevention for patients who already suffer from cardiovascular diseases. It is also very important in primary prevention for those healthy people who are at increased risk of cardiovascular disease.
2. Medical guidance issued by global bodies concerned with heart health constantly and relentlessly emphasizes the necessity of achieving a reduction in harmful LDL cholesterol. This is achieved in a way that is medically described as “more than wonderful,” by taking statin medications, by reducing the liver’s production of cholesterol. This makes them “first-line drugs” for treating high cholesterol, not only as a result of their historically proven record of clearly reducing low cholesterol in the blood, but more importantly, is their success in reducing the rates of atherosclerosis and narrowing of the heart disease (Morbidity), and the deaths resulting from it (Mortality). .
As an example, large, large-scale studies have found that continuous statin therapy over 5 years progressively reduces cardiovascular disease and atherosclerosis-related relapses by 21 percent for every 1 mmol/L reduction in LDL cholesterol (about 40 mg/dL). ).
Statin intolerance
3. However, many patients suffer from side effects that prevent them from using a statin drug at all, or limit their ability to tolerate the dose necessary to achieve their cholesterol goals, and this is medically called “statin intolerance.” Thus, it hinders achieving the desired goal of reducing cholesterol levels to the rates required therapeutically. Because suboptimal cholesterol control leaves them at ongoing cardiovascular risk, these patients should be carefully evaluated for statin intolerance, and adjuvant or alternative therapies should be considered.
According to what medical statistics indicate, observational clinical studies indicate that the problem of “statin intolerance” may reach 30 percent among groups of patients who take one of these types of cholesterol-lowering medications. The American National Lipid Association (NLA) first proposed a working definition for this condition in 2014, and in late 2022 the association provided an updated definition about its prevalence and management. This was published in the August 17 issue of the Journal of the American College of Cardiology (JACC).
4. Statin intolerance refers to a set of adverse symptoms and signs experienced by patients associated with statin therapy. The most common complaints were various muscle symptoms, with 60 percent of them having muscle symptoms as the main reason for discontinuing the drug. Symptoms of myopathy, according to the American National Lipid Association, include pain, aches, weakness, and muscle cramps. The association adds that it typically affects the symmetrical (on both sides) and major and proximal muscle groups near the middle of the body. Myopathy problems with statin medications usually take three aspects…
– Muscle pain (Myalgia) only, which usually appears without an increase in muscle enzyme (CK), which is common, especially in women.
– Myositis only, which appears with an increase in the muscle enzyme (CK), and occurs at a rate of 1 in every 10,000 patients who take these medications annually.
– Rhabdomyolysis.
5. Regarding rhabdomyolysis, Dr. Francisco Lopez-Jimenez of the Mayo Clinic explains this truly serious condition, saying: “Although mild muscle pain is a common side effect of statins, some people who take statin medications may experience severe muscle pain.” . This severe pain may be a symptom of rhabdomyolysis, a rare condition that causes muscle cells to break down.
The most common signs of rhabdomyolysis may include severe muscle pain throughout the entire body, muscle weakness, and dark or cola-colored urine. The higher the statin dose, the greater the risk of rhabdomyolysis. However, the risk of developing rhabdomyolysis is very low, at about 1.5 percent among every 100,000 people who take a statin. Rhabdomyolysis or less severe forms of statin-induced myositis can be diagnosed with a blood test to measure levels of the enzyme creatinine kinase.
If you experience signs and symptoms of rhabdomyolysis, stop taking statins immediately and receive medical treatment immediately. If necessary, your doctor may take steps to help prevent kidney failure and other complications.
Complications of pain and difficulty in diagnosis
6. The mechanism by which statin drugs cause muscle symptoms is not well understood. But it is not thought to always be directly and exclusively attributable to statin use. Because the National Lipid Association’s statement reiterates that “other potential and modifiable contributors, in addition to statins, to these muscle problems include vitamin D deficiency, drug interactions with other medications taken by the person, excessive alcohol use, or deficiency.” Thyroid. These must also be evaluated and corrected wherever possible.”
Under the title “Statin-Associated Myalgia,” a group of Cleveland Clinic doctors state in one of their scientific articles (the July 2021 issue of the Cleveland Clinic Journal of Medicine) that: “Risk factors for developing statin-associated myalgia have been identified. Including advanced age, female gender, family history of statin-related myalgia, alcohol abuse, and rheumatic diseases. Some medications can increase the risk; Colchicine, verapamil, diltiazem, fibrates, protease inhibitors, azoles, antimicrobials such as clarithromycin and erythromycin.”
7. The clinical diagnosis of this condition is difficult, as no signs have been identified that can be detected by any specific blood analysis. Muscle enzyme (creatine kinase) levels, thyroid function, inflammatory markers, and vitamin D are usually normal. Furthermore, definitions of myopathy, myalgia, myositis, and rhabdomyolysis vary among international medical bodies. In their aforementioned article, Cleveland Clinic doctors say: Although there are no standardized definitions, some diagnostic criteria are consistent across published guidelines. Factors that suggest a clinical diagnosis of statin-associated myopathy include…
– Pain or weakness in nearby large muscles, worsened by exercise.
Symptoms begin 2 to 4 weeks after starting to take a statin.
– Symptoms disappear within two weeks of stopping.
Symptoms return within two weeks after retaking statins.
Symptoms appear when taking two or more different types of statins, at least one of which is prescribed at the lowest dose.
8. The consequences of statin intolerance come with significant health and financial costs. This is because patients who are intolerant to statins, and whose medications are down-titrated or discontinued, are at greater risk of developing cardiovascular disease in the future. A large clinical study found that patients with statin intolerance had a 36 percent higher rate of recurrent heart attack compared with those who continued statin treatment. They were 43 percent more likely to suffer relapses of coronary heart disease. The financial costs of treating patients with statin intolerance are higher when compared to people receiving statin therapy.
The problem of “statin intolerance” may appear in 30% of groups of patients
4 steps for therapeutic treatment of “statin intolerance”
The patient needs to realize that the clinical management of statin intolerance goes through the following steps…
– Confirm statin intolerance. In a patient with suspected statin intolerance, statin treatment should be discontinued and symptoms monitored over a period of two weeks to see whether they resolve. After two weeks, if symptoms disappear, the same statin may be restarted at a lower dose or an alternative statin medication may be prescribed.
– Use of another statin medication. The pharmacological profiles can vary greatly between statin class drugs, including lipophilic statin types and hydrophilic statin types. Therefore, among the drugs in the statin class, there are different types of drugs that spread to tissues outside the liver, such as muscle. Simvastatin, a lipophilic statin, is significantly associated with muscle symptoms. In contrast, hydrophilic statins are efficiently transported to hepatocytes. Examples include pravastatin and rosuvastatin, which are less associated with muscle symptoms. Therefore, switching from a lipophilic statin to a hydrophilic statin is a reasonable alternative first-line pharmacological strategy for patients with myalgia.
– Adjust the dose. Intermittent dosing rather than daily dosing may also be considered for patients with statin-associated muscle symptoms, and for patients with a history of severe muscle toxicity and marked elevation of creatine kinase. Studies have found that intermittent dosing can achieve reductions in LDL cholesterol of about 20-40 percent. However, the effects of this therapeutic behavior on cardiovascular outcomes have not yet been determined.
– Treatment with non-statin medications. For patients with persistent symptoms, even after trying two different types of statins at the lowest doses, they are likely to be completely intolerant to them in the future. Then non-statin medications should be taken into consideration, including…
. Ezetimibe, which was approved by the US Food and Drug Administration in 2002, prevents the absorption of cholesterol in the intestine. Ezetimibe is the most widely used non-statin drug, which reduces LDL cholesterol levels by up to 20 percent at best.
. Bempedoic Acid was approved by the US Food and Drug Administration to treat high cholesterol in 2020. It works by inhibiting an enzyme important for the liver’s production of cholesterol. Many studies are still being conducted about it.
. PCSK9 monoclonal antibody inhibitors. It is a new class of treatment that lowers LDL cholesterol by up to 60 percent. It reduces the risk of cardiovascular disease. Many studies have proven the effectiveness of PCSK9 inhibitors in patients with statin-associated muscle symptoms. The results demonstrate that treatment with a PCSK9 inhibitor is a promising and superior alternative strategy for lowering mild cholesterol in patients with statin intolerance.
2024-02-15 13:47:41
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