Cost-effectiveness ratio of cholesterol level control

Cost-effectiveness ratio of cholesterol level control

The cost-effectiveness of non-pharmacological interventions to reduce LDL cholesterol is unclear. Pharmacological interventions are clearly cost-effective in certain conditions, and the available data allow selecting recommendations taking into account the initial risk of CHD. Early analyzes of cholesterol reduction for the purpose of secondary prophylaxis, in which data from cholesteramine studies were used, showed a very high cost of interventions, largely due to the fact that the available drugs were ineffective. On the contrary, a recent analysis of the results of statin therapy after the addition of two more generic drugs in 2006 showed that they are cost-effective for a larger number of individuals.

Before the advent of generics Prosser L.A. et al. used data from several large, long-term, randomized, controlled studies of statin Coronary Heart Disease Policy. When using statins in primary prevention, it was not possible to achieve a cost-effectiveness ratio of $ 50,000 for QALY in none of the subgroups ($ 1.4 million for QALY). In secondary prevention, the cost-effectiveness ratio was in the range of $ 1,800 for QALY for men 45-54 years old and $ 40 thousand for women 35-44 years old. Statin therapy has also been cost effective for patients 75-84 years of age.

All QALY scores are very sensitive to the cost of drugs, and it can be expected to noticeably decrease as the generics appear. Simvastatin and pravastatin became available as generics in 2006, in addition to lovastatin, which has been prescribed in the form of a generic since 1999. A recent analysis showed that a generic simvastatin at a dose of 40 mg / day can reduce the cost of a saved life by $ 1,350 per year among people at risk vascular events> 1% regardless of age at the start of treatment.

The benefits of cholesterol control

The benefits of cholesterol control

A clear benefit has been demonstrated in relation to diet and drug therapy aimed at reducing serum cholesterol (cholesterol). A large number of large-scale studies on primary and secondary prevention with the use of HMG-CoA reductase inhibitors (statins) have demonstrated a significant reduction in the incidence of CHD and MI in various populations. The studies included patients with established CHD; with KBS and other occlusal PAD or DM, but normal levels of cholesterol; without clinically overt atherosclerotic CVD and with moderate levels of cholesterol and LDL cholesterol; elderly people at risk of vascular diseases and people with hypertension with moderate or low levels of cholesterol.

A meta-analysis of 2005, which included 14 randomized clinical trials (n = 90,056), showed that statin therapy safely reduced the 5-year incidence of major coronary events, coronary revascularization and MI by 20% while LDL cholesterol decreased by 1 mmol / l, regardless of its baseline, age, gender, or previous disease, and without any increase in the incidence of cancer. This risk reduction is linear, resulting in a comparable risk reduction across the entire lipid spectrum.

Prolonged daily adherence to therapy is likely to be more important in determining final efficacy than any differences between the effects of statins. A recent analysis of 4 large randomized studies of patients already having the disease showed that intensive therapy with large doses of statins clearly exceeds the effectiveness of standard dose treatment in reducing the risk of MI, cerebral stroke (MI) or any cardiovascular event (SSSob). Some researchers, but not all, support the early prescription of statin therapy after myocardial infarction or coronary artery bypass grafting.

Gemfibrozil (a drug that increases HDL cholesterol and reduces TG levels) reduces the risk among people with high levels of cholesterol and LDL cholesterol. In the VA-HIT study (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial), a 22% decrease in cardiovascular events (SSSob) was observed in the treatment of gemfibrozil in persons with low cholesterol cholesterol (<40 mg / dL, or 1 mmol / L) , and this risk reduction occurred in the absence of any significant change in the content of LDL cholesterol. These data confirm the ability of drugs to influence cholesterol and HD. Nicotinic acid can increase the level of cholesterol cholesterol and reduce ssob associated with coronary artery disease.

Another class of drugs that can increase the level of cholesterol-free cholesterol is currently in a clinical trial. BPHEC inhibitors can increase the level of HDL cholesterol and moderately reduce the level of LDL cholesterol. However, despite the expectation of positive outcomes for disease outcomes from the use of BPECS inhibitors in combination with statins, the recent cessation of the development of one of BPECS inhibitors, associated with its apparent PE, underscores the need for long-term clinical trials on the effect of BPECS inhibitors on HDL cholesterol.

Prevalence of hypercholesterolemia.

Prevalence of hypercholesterolemia.

Since the early 1960s. the average cholesterol level among the US population has slightly decreased. But even with this reduction, 50% of American adults have cholesterol levels> 200 mg / dl, and 17% have cholesterol levels> 240 mg / dl. Low levels of HDL cholesterol and high levels of TG have a tendency to coincide and are often the result of metabolic changes leading to high levels of LDL cholesterol. Low levels of HDL cholesterol and high concentrations of TG can be observed separately or in combination with high LDL cholesterol.

Associated risk. Some cholesterol parameters have a causal relationship with an increased risk of CHD. An increase in serum LDL cholesterol by 1 mg / dL is associated with an increase in the risk of CHD by 2-3%, and at a young age, an elevated LDL cholesterol content may be associated with an even greater increase in risk. HDL has become an important independent predictor of KBS, a decrease in cholesterol cholesterol by 1 mg / dL leads to an increase in the risk of KBS by 3-4%. The ratio of total cholesterol or LDL cholesterol to cholesterol cholesterol predicts the risk of CHD better than LDL cholesterol.

Reducing this ratio by 1 unit (which can easily be achieved by prescribing statins) reduces the risk of myocardial infarction by 50%. The ratio of total cholesterol to cholesterol may be better than the ratio of apo A to apo B. The level of cholesterol also predicts risk well, since Non-HDL cholesterol correlates well with apo B, therefore costly definition of apo B is not necessary.

Inaccuracies in the determination of triglycerides (TG), intraindividual fluctuations, dependence on diet, and complex interactions between TG and other lipid parameters may disguise the contribution of TG to the development of CHD. However, the fasting TG level correlates with the risk of CHD, especially when the content of cholesterol cholesterol is taken into account. This interdependence suggests that some TG-rich lipoproteins are atherogenic. Some studies have suggested that elevated TG concentrations are an independent predictor of KBS. The clinical significance of TG, not assessed by fasting, remains unclear.

The ratio of the cost-effectiveness of quitting.

The ratio of the cost-effectiveness of quitting.

The ratio of the cost-effectiveness of quitting. The ratio of cost-effectiveness of smoking cessation is very high in both primary and secondary prevention. Intervention is usually short term and low cost. Indeed, smoking cessation is cheaper than continuing to smoke. The increase in life expectancy is large, and the earlier a person quits smoking, the greater will be the increase; for example, a 35-year-old man after smoking cessation may add to a life expectancy of 3 years.

The cost varies depending on the intensity of the intervention and the use of drugs. A Swedish study found that over a 20-year observation period, the cost of a single life saved was relatively low for bupropion compared to a nicotine patch: $ 660 for men and $ 490 for women. Some non-pharmacological approaches have also proven to be effective.

e) Guidelines and recommendations. In the U.S. clinical guidelines. The Public Health Service recognized that tobacco dependence is a chronic condition and repeated intervention is usually necessary. It is recommended that the patient be asked about smoking at each visit; U.S. also supports this strategy. Preventive Services Task Force. The U.S. manual. Preventive Services Task Force is recommended when necessary combined intervention: counseling and drug therapy. Three types of counseling and behavioral therapy are particularly effective:

(1) training;

(2) social support for treatment;

(3) social support outside treatment.

There are 6 types of first-line drug therapies that reliably increase the duration of abstinence from smoking: prolonged-release bupropion hydrochloride, nicotine tablets, chewing gums and patches, inhalers and nasal sprays.

Due to tobacco dependence and the tendency to increase in smoking over time, reducing the number of cigarettes is an unacceptable strategy. The effectiveness of interventions ranges from 6% during the year when advised by a doctor to 18% when performing self-help programs and 20-40% with pharmacological intervention using a nicotine chewing gum or patch.

It is important to reasonably explain to the patient the harm of smoking and the benefit of quitting at all stages of therapy, and the period immediately after the cardiovascular event (SSSob) is the optimal time for quitting smoking.

f) Perspective directions. In the United States, smoking cessation efforts will continue, but intensive public health efforts around the world are needed to reverse the dangerous growth trend of smoking in developing countries; for example, 60% of men in China today smoke. Of the 1.1 billion smoking population, 82% live in low- or middle-income countries. The low frequency of success of smoking cessation interventions is a challenge for clinicians, so you should focus on smoking prevention.

The effectiveness of quitting smoking in coronary heart disease

The effectiveness of quitting smoking in coronary heart disease

This category includes 4 primary interventions: smoking cessation, control of dyslipidemia (DLP) and blood pressure, as well as prophylactic administration of drugs by individual patients. Each intervention should be seriously discussed with patients with CVD, diabetes, as well as with patients suitable for primary prevention. This discussion should be documented.

a) prevalence. In the US, cigarette consumption in terms of 1 person. grew dramatically in the first half of the twentieth century. By 1945,> 65% of men born in 1911-1920 smoked. The annual per capita consumption of cigarettes in 1963 reached 4,286 (> 200 packs per year), but has since dropped to 1875. The prevalence of smoking among men reached a peak in 1955, when> 50% of men smoked; in women, the peak came 10 years later.

Since then, the prevalence of smoking among Americans has decreased significantly (to 21%). Currently, 23% of men and 18% of women are smokers in the population> 18 years old. The frequency of smoking among older schoolchildren increased from 30% in the mid-1980s. to 36.5% in 1997, moreover at the expense of girls, but now it is gradually decreasing. The frequency of smoking is higher among people with low socioeconomic status and educational qualifications.

b) Associated risk of smoking. Smoking increases the risk of coronary heart disease (CHD). By the middle of the XX century. The first studies that linked smoking to heart disease were published.

A 1964 Surgeon General’s report confirmed this epidemiological link, and in 1983 Surgeon General’s firmly named cigarette smoking as the main preventive cause of cardiovascular diseases (CVD). The 1989 Surgeon General’s report provided accurate data from case-control observational studies and cohort studies, mostly among men. It is established that smoking increases the frequency of CHD by 2 times and by 50% the mortality from CHD, and this risk increases with age and the number of cigarettes smoked. A similar increase in the relative risk of KBS is observed among women.

In the US, cigarette smoking is the leading modifiable cause of deaths (438 thousand deaths annually, of which 35% is cardiovascular death) and losses> 5 million years of life. Worldwide, the frequency of smoking continues to grow, with the most in developing countries; in 2000, deaths from tobacco smoking were more than 1 million compared with 1990.

c) The benefits of stopping smoking. Evidence from large-scale, randomized, risk-reduction trials of smoking cessation is limited, but observational studies have shown a clear benefit of stopping smoking. People who quit smoking reduce the excess risk of coronary events during the first 2 years by 50%, with the greatest benefit observed in the first few months. This period is followed by a gradual decrease, and after 3-5 years the risk among those who smoked earlier approaches the risk of those who have never smoked.

Coronary heart disease as a multifactorial disease

Coronary heart disease as a multifactorial disease

Knowledge of the biological mechanisms of atherosclerosis led to an understanding of the progression of this disease and many of its etiological factors. Coronary heart disease (CHD) develops as a result of the interaction of many RFs.

Often, people with cardiovascular diseases (CVD) simultaneously have small changes in several risk factors (RF), rather than extreme deviations in the level of one. If these risk factors (RF) are not controlled, then atherosclerosis will continue to develop. Predisposing RF, for example, genetic, interact with behavioral RF, such as diet, alcohol consumption and physical activity.

The combination of these predisposing and behavioral factors can cause metabolic changes – dyslipidemia (DLP), hypertension, obesity and diabetes, which ultimately lead to a pronounced disease. The key point in identifying susceptibility to this disease may be various diagnostic tests. Some tests that assess physical changes in the arteries, such as the thickness of the TCIM CA or the presence of calcium in the CA, can be used to assess the severity of atherosclerosis, while an exercise test helps diagnose stenosis of the ischemia.

Other tests, such as determining the level of chrish, suggest the likelihood of a cardiovascular event (SSSob), but may not clearly correlate with the severity of atherosclerosis. This latent disease can manifest as a transient ischemic attack (TIA), MI, or another Ssob. DFs useful for prediction, both modifiable and non-modifiable, can be identified at any stage of this process. For example, FRs are hereditary predispositions for heart disease and smoking. Such a metabolic factor, such as a high level of LDL, also serves as a risk factor.

Migrated IM or MI is also a strong predictor of future events. This reflects the relationship between predisposing risk factors (RF) and disease markers, which may be important for identifying people at increased risk of developing clinical complications.

Risk assessment (RF) is useful, but sometimes they are conditional, i.e. they are difficult to classify as a specific category. For example, hereditary predisposition may be in the presence of certain genes in the descendants, but also in the lifestyle of the family, which passes from one generation to another.

It is not known whether hypertension is a consequence of the influence of such features of a family lifestyle as a diet predisposing to atherosclerosis, low physical activity (NFA), or is it a manifestation of ED, thus serving as a marker of atherosclerosis.

Risk assessment of coronary heart disease (CHD) in the office

Risk assessment of coronary heart disease (CHD) in the office

Clinicians can easily classify in their patients the long-term risk of coronary heart disease (CHD) and other cardiovascular events (SSSob) as very high, high, intermediate or low based on answers to a few simple questions and manipulations, such as measuring blood pressure. An algorithm was developed that allows to classify patients according to their total cardiovascular risk (SSR).

The patient’s cardiovascular status is the first issue of the algorithm. If the patient has cardiovascular disease (CVD), then it is necessary to determine whether it is stable. If yes, then further classification is not necessary, because this patient by definition has a very high long-term risk and needs an “aggressive” modification of a risk factor (RF).

The presence of instability, such as unstable angina (NS), indicates a high short-term risk. Unstable patients need immediate referral for appropriate diagnostic studies and interventions. Even after the stabilization of the debt state, the acute risk of these patients is very high.

If the patient does not have an established CVD, but there are worrisome symptoms (for example, recurring chest pain, suggesting CVD or another CVD), then this patient also needs to be evaluated using appropriate diagnostic tests to detect high short-term risk. If CVD is diagnosed, the patient should undergo further examination, for example, catheterization or other intervention (if necessary), and further should be assigned to a very high risk group. If the results of this examination are negative, the patient is returned to the primary prevention group for risk assessment.

For those who do not have CVD, the key point is the presence of diabetes. If diabetes is diagnosed, then the long-term risk is high and the patient should be classified as a high-risk group for primary prevention. According to the algorithm, patients without obvious CVD or diabetes must undergo a test to determine the 10-year risk of CVD using a simple prognostic tool, such as the Framingham Risk Scale or another similar scale.

Patients with very high Framingham Risk Scores (CSD risk for 10 years> 20%) are also at high risk. On the other side of the spectrum are patients whose risk factors (DF) are <2 or the Framingham risk score is <5%. These patients are classified as low risk.

According to the algorithm, for patients who fall into the intermediate group or are between high and intermediate risk (10-year risk is 5-15%), clinicians may collect additional information for better stratification: conduct a secondary screening if it is unclear how “aggressive” there should be an intervention aimed at FR. The next step for such patients is to determine the level of CRP, and a more expensive and complicated method may be a test for TFN or EDT to determine the calcium content in the coronary arteries (DND and USPSTF approved the prescription of the FN test for a prevention decision).

Each of these tests provides additional information to the Framingham Risk Scale. CRP may be helpful, but it is unlikely that intervention will be needed, the significance of which in asymptomatic patients is unknown. The end result will be a more accurate risk assessment and the assignment of the patient to the relevant group (high, intermediate or low risk). Such a general risk classification is useful in choosing an intervention and its intensity.

Risk factors

Risk factors

In 2003, the New Zealand Guidelines Group was updated, creating tables that estimate the 5-year total SSR based on age, gender, ethnic group (Maori or non-Maori), smoking status, lipid levels, glucose and blood pressure (Fig. 45- five). Patients are stratified as having a very high, high, moderate, and low risk. Patients with established CVD, genetic lipid disorders, diabetes, or kidney disease constitute a very high risk group because have a> 20% risk of a follow-up SWS for 5 years. “Aggressive” intervention is recommended for patients with SSR> 15%.

There are small differences between different prognostic scales, they classify patients equally and are an inexpensive initial method of risk assessment. Life-long risk is an important method of risk-reflecting, especially for the young, for whom an early lifestyle change is essential.

Diagnostic tests and new biochemical markers designed for patients with specific complaints can enhance the predictive capabilities of simple scales. Such diagnostic tests are the determination of calcium mass by CRT and the exercise tolerance test (TFN). EchoCG and cardiac catheterization can provide additional prognostic information, but these tests are quite expensive and have potential harmful effects, and their use in prevention remains controversial.

A marker of inflammation CRP may increase the prognostic value of initial screening.

The Women’s Health Study recently showed that adding such simple variables as family history, HbA1C levels in diabetes and CRP, allows almost 50% of women in the intermediate-risk group to qualify for a higher or lower group. This reclassification turned out to be correct in almost all cases, at least according to comparison with the traditional risk criteria ATP III.

Thus, improved risk prediction algorithms should help ensure that preventive treatment, based on both lifestyle changes and drug therapy, is correctly applied in the appropriate group of patients.

General and individual risk scales

General and individual risk scales

Due to the fact that many predictors of risk correlate with each other, risk can often be predicted based on information about several risk factors (RF). In most cases, many risk factors (RF) can be identified during initial screening, but it is sufficient to identify several easily measurable risk factors (RF) to calculate the overall risk for coronary heart disease (CHD).

For those who, at the initial screening, the risk is very low or very high, the measurement and evaluation of additional risk factors will give very little useful information, i.e. additional screening will add valuable information only in patients with intermediate risk. Evaluating individual absolute risk will allow you to select cost-effective intervention.

As evidence of the importance of assessing individual risk, NCEP, ATP III, JNC-7, and USPSTF suggested several options for assessing individual risk to determine the intensity of various interventions. The American Diabetes Association also recommends an absolute risk based treatment approach.

Usually, the presence or absence of cardiovascular disease (CVD) is sufficient for the distribution of patients with high or low risk. Patients with established CVD, such as damage to the coronary artery, cerebrovascular or peripheral arteries, constitute the first high-risk group. They always have a higher average risk than those without CVD. Approximately 80% of patients with established CVD will die from this disease, while among those without an established CVD, the death rate will be only 50% of the mortality rates from CVD.

As discussed later in this chapter, people with CVD usually need more “aggressive” interventions. Reducing the risk in these patients refers to secondary prevention, and among those without obvious CVD to the primary.

Patients with diabetes

Patients with diabetes

Patients with diabetes constitute the second high-risk group. The frequency of cardiovascular events (SSSob) and mortality among patients with diabetes is much higher than in the general population, so these patients need “aggressive” preventive interventions. The third group of patients who are at high risk for SCSS and death are patients with CKD, many of whom suffer from diabetes.

For patients without CVD and diabetes, several risk determination strategies based on risk factors (RF) have been developed. Early versions of some manuals recommended a simple calculation of DF. The Framingham Heart Study researchers have developed a handy tool for assessing the risk of a first SSSob, taking into account age, gender, cholesterol, LDL, LDL, GL, DAD, diabetes, and smoking. Points are assigned if and depending on the level of each FR.

After the summation of points, the absolute risk of coronary heart disease (CHD) is assessed over the next 10 years. The National Heart, Lung, and Blood Institute posted an affordable online 10-year risk calculator. Researchers at the Framingham Heart Study also developed scales for determining the risk of secondary prevention of MI and MI. However, due to the fact that patients with CVDs already have a high risk of recurrent CVDs and need “aggressive” prevention, the benefits of this tool remain unclear.

There are several alternatives to the Framingham risk scale. The HeartScore project (Heart Systematic Coronary Risk Evaluation) was created by a European working group based on cohort studies involving> 200 thousand people in 12 European countries.

HeartScore replaced the earlier risk stratification patterns common to the European Society of Cardiology, and shifted the focus from warning KBS to warning CVD. On the basis of age, sex, SAD, CHF, or HCV HDL ratio, HeartScore calculates the 10-year risk of death from CVD, rather than the risk of individual cardiovascular events (SSSob). SD in this scale was not included, because he was not studied in the cohorts used to create the scale. For patients with a 10-year risk of fatal events> 5%, aggressive intervention is recommended.

Another risk assessment tool was created based on the PROCAM study, which for a long time (from 1979 to 1985) monitored for> 5 thousand men aged 35–65 years. In the PROCAM FR algorithm, there were smoking, GARDEN, LDL CH and HDL cholesterol, fasting TG, as well as diabetes, MI in the family history and age. Answers in points to questions regarding these DFs are summarized, as in the Framingham risk scale, and the 10-year absolute risk of fatal or nonfatal IM BCC is determined by the results.