Effectiveness of β-adrenergic blockers in coronary heart disease

Effectiveness of β-adrenergic blockers in coronary heart disease

A number of studies have demonstrated the effectiveness of β-AB in reducing mortality with long-term use after myocardial infarction (MI); according to meta-analysis, this reduction is 23%. Long-term use of beta-blockers also reduces the risk of repeated cardiovascular events (SSSob).

A comparison of cross-sectional studies showed that the higher the β-blockade level (decrease in heart rate compared with the control group), the greater the benefit, β-blockade after myocardial infarction (MI) and in CHF is extremely cost-effective.

According to the Coronary Heart Disease Policy Model, the use of β-AB during the year by all patients after the first MI will prevent 62 thousand of MI and reduce by 72 thousand the number of deaths from coronary heart disease (KBS) within 20 years. The ratio of cost-effectiveness of β-AB therapy is <$ 11 thousand for QALY.

Beta-blockers such as carvedilol and metoprolol reduce mortality in patients with chronic heart failure (CHF).

Aspirin in primary prevention.

Aspirin in primary prevention.

In 6 large-scale studies, the effect of low doses of aspirin in the prevention of cardiovascular diseases (CVD) was evaluated. In 3 studies only men were included, in 1 – women. The pooled data from these studies suggested a beneficial effect of aspirin in the prevention of myocardial infarction (MI) and ischemic cerebral stroke (MI).

The WHS (Women’s Health Study) study evaluated the risk-benefit ratio of aspirin therapy in primary prevention in women. In this study, taking 100 mg of aspirin through laziness reduced the risk of cerebral stroke (MI), but did not affect the risk of myocardial infarction (MI) or death from cardiovascular disease (CVD) in initially healthy women aged> 45 years. However, in women> 65 years, taking 100 mg of aspirin every other day reduced the risk of major cardiovascular events (SSSob) by 25%.

In this study, the dose of aspirin <75 mg was also studied, the effect of which was suboptimal. An unreliable decrease in cardiovascular events (SSSob) by 9% coincided with an unreliable decrease in risk by 13% for secondary prevention with aspirin at a dose of <75 mg, according to meta-analysis data.

In 2002, the USPSTF and the ANA concluded that aspirin reduces the incidence of new cases of coronary heart disease (CHD) in high-risk adults. The USPSTF found that among those with a 10-year risk of> 6%, the benefits of taking aspirin outweigh the increased risk of gastrointestinal bleeding or hemorrhagic MI.
In 2004, the ANA recommended the use of aspirin by women whose 10-year risk of the first coronary event is> 20%, but the use of aspirin at risk in the range of 10-20% needs to be studied. The European Society of Cardiology recommends low doses of aspirin (75 mg / day) in primary prevention only for men with very high coronary heart disease (CHD).

The effectiveness of taking aspirin for coronary heart disease

The effectiveness of taking aspirin for coronary heart disease

Some pharmacological interventions have proven to be highly effective in preventing cardiovascular diseases (CVD). Reducing the risk during or immediately after the development of coronary heart disease (CHD) was achieved with the help of aspirin, β-AB and ACE inhibitors. Each of these drugs was effective in long-term secondary prevention among various subgroups of patients, and aspirin was effective for some groups and in primary prevention.

Aspirin for secondary prophylaxis. Aspirin therapy in patients with an already existing cardiovascular disease (CVD) reduces the risk of subsequent events by 25%. Meta-analyzes showed a clear decrease in mortality and non-fatal cardiovascular events (SSSob) among patients after myocardial infarction, cerebral stroke (MI), coronary artery bypass surgery (CC), angioplasty, peripheral artery surgery or angina.

In these meta-analyzes, it was found that doses of aspirin> 75 mg / day are effective, but a further increase in doses was not accompanied by an increase in efficiency. Conversely, doses of <75 mg / day resulted in an unreliable risk reduction of 15%. However, ACC / ANA recently reduced prophylactic doses of aspirin from 75-325 to 75-162 mg / day, based on anti-platelet studies that revealed no differences in efficacy at lower doses, but showed a reduction in the risk of bleeding.

Other antiplatelet drugs have no advantage over aspirin. In the analysis of ATS (Antiplatelet Trialists Collaboration), such drugs also did not have superiority. It is unclear whether clopidogrel has a slight advantage. Despite randomized trials involving thousands of patients and data on the comparative cost of drugs, their effectiveness is unclear. A recent study comparing the combination of clopidogrel and aspirin with aspirin monotherapy among high-risk patients did not reveal the benefits of combination therapy in reducing the incidence of MI, MI, or death from CVD, but the combination therapy increased the risk of both small and severe bleeding.

Although there is evidence to add aspirin to clopidogrel for some high-risk patients, such as acute ischemia or after stent placement, an increased risk of bleeding makes this strategy unacceptable for primary prophylaxis.

In the absence of contraindications, aspirin should be used for all patients with cardiovascular diseases (CVD). Other antiplatelet drugs with proven efficacy, such as clopidogrel, should be prescribed to patients who are allergic to aspirin or are intolerant. Cost-effectiveness for clopidogrel is less favorable than for aspirin; in addition, clopidogrel is associated with an increased risk of hemorrhage; therefore, clopidogrel should not be used instead of aspirin for primary prophylaxis. The data of the Coronary Heart Disease Policy Model showed that with the expansion of aspirin for secondary prophylaxis from the current level to reception by all patients, to whom it is indicated, the cost-effectiveness indicator for 25 years will be $ 11 thousand for QALY.

Recommendations and treatment of arterial hypertension

Recommendations and treatment of arterial hypertension

The USPSTF expert group recommended a routine measurement of blood pressure in all adults. JNC-7 recommendations identify four levels of BP according to risk. JNC-7 intervention guidelines are based on levels of blood pressure and absolute risk. Absolute risk stratification is carried out according to the presence or absence of POM, clinical CVD, DM or cardiovascular RF, such as smoking, dyslipidemia (DLP), age> 60 years, gender, early CVD in the family history. JNC-7 recommendations set a target blood pressure level of <140/90 mmHg. st. for patients with low risk and <130/80 mm Hg. st. – for those suffering from CVD, diabetes or chronic kidney disease.

Since the association of blood pressure with a cardiovascular risk is straightforward, a significant part of the population attributable risk is in people with blood pressure, who, according to JNC-7, are classified as prehypertension, AAD = 120–139 mm Hg. Art., and DBP = 80-89 mm Hg. st.

For all persons with blood pressure> 120/80 mm Hg. st. JNC-7 recommends lifestyle changes, including smoking cessation, weight loss, if necessary, increasing FA, limiting alcohol and salt, maintaining adequate intake of potassium and calcium, using the DASH dietary strategy, i.e. diets with a reduced content of saturated fatty acids and total fat, but rich in fruits, vegetables, and low-fat dairy products.

The initiation of drug therapy depends on the levels of blood pressure and absolute risk. For example, for people with hypertension I degree, but without signs of organ damage, vascular disease or diabetes, and with a cardiovascular risk factor alone, lifestyle changes and drug therapy are recommended. For persons with hypertension of II degree, a combined initial therapy, usually including diuretics, is necessary. The guide also recommends starting therapy with two drugs, one of which is a diuretic, when blood pressure is above the target level at> 20/10 mm Hg. st. The specific therapeutic drugs recommended by JNC-7 are discussed in detail in a separate article on the site – we recommend using the search form in the sidebar of the site menu.

For most patients, more than one drug is required to reach the target level.

The European Society of Cardiology guidelines have otherwise stratified initial therapy. High normal blood pressure is determined when GAD = 130-139 mm Hg. st. or DBP = 85-89 mm Hg. Art., and drug therapy is recommended only for this group of patients if they have a very high risk due to a history of MI, TIA or a similar clinical condition. Among patients with hypertension I degree (CAD = 140-159 mm of rg. Art. Or DBP = 90-99 mm Hg. Art.) Or hypertension of II degree (CAD = 160-179 mm Hg. Or DAD = 100-109 mmHg. Drug therapy should be started immediately for people at high risk (RF> 3, POM or DM) or at very high risk (obvious clinical disease).

For patients of the other two groups (with moderate and low risk), a lifestyle change with continuous monitoring (at least 3 months) is recommended. If the CAD is still> 140 mmHg. st. or dad> 90 mm Hg. Art. Drug therapy should be prescribed to patients at moderate risk and should be considered for those at low risk. As with the JNC-7 recommendations, lifestyle changes should always be recommended as an adjunct to drug therapy.

The results of ALLHAT also showed that a thiazide-like diuretic can be a good choice as an initial antihypertensive therapy (AGT). The use of β-AB for primary prophylaxis as a first-line therapy has been carefully studied. The ASCOT-BPLA study included 19,257 patients with hypertension and a moderate risk of developing SSSob. The patients were divided into 2 groups:
(1) β-AB plus thiazide diuretic (if necessary);
(2) prolonged calcium antagonist plus ACE inhibitors (if necessary).

The study was terminated ahead of time, because it became apparent that over time, those taking β-AB fell into disadvantage. A meta-analysis of 20 studies showed that β-AB should not remain the drug of first choice in the treatment of primary hypertension.

In 2006, the British Hypertension Society revised the recommendations on drug therapy ahead of time to change the previous recommendations on β-AB as first-line drugs for the treatment of hypertension. The working group presented evidence that β-AB is not as effective as other drugs, especially in the elderly, and drew attention to the increasing evidence that β-AB in usual doses create an unacceptable risk of developing diabetes-2.

The benefits of normalizing blood pressure

The benefits of normalizing blood pressure

In the 1960s. A number of randomized clinical studies have confirmed the protective effect of treating mild and moderate hypertension. An accurate assessment of the risk reduction was obtained from meta-analyzes, which showed that the reduction of DBP by 5-6 mm Hg. st. reduces the risk of cerebral stroke (MI) by 42% and the risk of coronary heart disease (CHD) by 15%.

The ALLHAT study showed the effectiveness of thiazide diuretics compared with other antihypertensive drugs (AGP). Some advantage of diuretics was a slightly better reduction in blood pressure. ALLHAT was one of 29 randomized trials included in a 2003 meta-analysis that examined the effects of various blood pressure reduction regimens on major cardiovascular events (SSSob).

There were no significant differences between treatment based on ACE inhibitors, calcium antagonists, diuretics, or β-AB, although ACE inhibitors reduced blood pressure to a lesser extent. In addition, the ego study demonstrated a linear relationship between a decrease in blood pressure and a decrease in risk. For many patients, it is necessary to prescribe 2 drugs for initial therapy, especially for patients with more severe hypertension.

The ratio of cost-effectiveness of normalization of blood pressure. Detection and control of hypertension have a high ratio of cost-effectiveness in both primary and secondary prevention. However, more “aggressive” treatment of persons at high risk due to the presence of cardiovascular disease (CVD) or diabetes mellitus (DM), based on the cost-effectiveness relationship, is warranted.

In secondary prophylaxis for drugs such as diuretics and β-AB, the cost of QALY for patients with established coronary heart disease (CHD) was <$ 10,000, even if blood pressure was increased slightly. With primary prevention, the cost of QALY varies from $ 10 thousand to $ 20 thousand among those with moderate and severe hypertension. However, for more expensive drugs, the cost is close to the unacceptable value of $ 100 thousand for QALY.

The cost-effectiveness ratio decreases with age. Given this fact, a thorough assessment of the cost-effectiveness relationship is necessary to implement the recommendations of JNC-7, since they are encouraged to use several drugs and different interventions in different groups of patients, including those with a slight increase in blood pressure.

Prevalence of hypertension

Prevalence of hypertension

According to the definition of JNC-7, 65 million Americans have hypertension and another 59 million have hypertension. Increased blood pressure is more common among African Americans than with white-skinned individuals, and mostly among men. The prevalence of AH increases with age: from 7% at the age of 18-39 years to 66% at the age of> 60 years.

The data from the Framingham Heart Study showed that people with normal blood pressure at the age of 55 have the risk of becoming hypertensive during the rest of their lives, equal to 90%. In the United States, the prevalence of AH is increasing. Although control of hypertension in the 1990s. improved, especially among elderly patients, in general, it remains quite low (30%).

Associated with arterial hypertension risk. Studies have consistently identified an association of elevated SBP or DAP with an increased risk of cardiovascular disease (CVD). Metaanalysis of data from 61 prospective observational studies involving 1 million people. revealed a linear relationship between the value of blood pressure and the risk of vascular death among middle-aged and elderly people with a decrease in blood pressure below 115/75 mm Hg. st ..

AH is also associated with an increased risk of developing HF, MI, and kidney disease. The shape of the SSR curve is linear. For limes aged 40-70 years, each increase in the GARDEN by 20 mm of mercury. st. and dad at 10 mm Hg. st. 2 times increases the SSR (in the range from 115/75 to 185/115 mm Hg. Art.). SAD remains the best clinical predictor of risk.

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.