Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes the design and methodological features of a double-masked, randomized, placebo-controlled trial to determine whether administration of the HMG CoA reductase inhibitor lovastatin retards the progression or facilitates the regression of coronary atherosclerosis. The study population consists of coronary patients with a recent arteriogram that characterizes them as being at high risk for coronary progression and a baseline fasting total serum cholesterol > or = 5.7 mmol/L and < or = 7.8 mmol/L. Lovastatin, or matching placebo, are up-titrated from 20 mg to 40 mg to 80 mg/day during the first 16 weeks of the study in an attempt to attain a fasting serum LDL cholesterol level of 3.4 mmol/L; patients and study personnel remain masked as to cholesterol levels throughout the trial. Coronary arteriography is repeated at 2 years, or earlier if necessitated by worsening symptoms, and all segments are measured quantitatively using a computer-based system. The primary outcome of the trial is a comparison between the lovastatin and placebo groups for coronary change score, defined as the mean of the minimum lumen diameter changes for all lesions (follow-up minus baseline arteriogram) per patient. The advantages and limitations of coronary arteriographic trials and some of the issues related to outcome measurements are discussed. The question posed by this study is of clinical relevance because the consequences of progression of coronary disease, angina, myocardial infarction, and sudden cardiac death are leading causes of morbidity and mortality.
 ...
PMID:Design features of a controlled clinical trial to assess the effect of an HMG CoA reductase inhibitor on the progression of coronary artery disease. Canadian Coronary Atherosclerosis Intervention Trial Investigators Montreal, Ottawa, and Toronto, Canada. 844 94

1. Recent outcome trials suggest that lipid-lowering with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors is justifiable on risk-benefit grounds in subjects with serum cholesterol > 5.5 mmol/l who have coronary heart disease, other forms of atherosclerotic vascular disease, or who are free of vascular disease but have a risk of major coronary events > or = 1.5% per year. Choice of an appropriate treatment policy will require (i) knowledge of the proportion of the population who will need treatment for secondary prevention, and (ii) targeting of treatment for primary prevention at a specified absolute risk of coronary heart disease events. Selection of an appropriate coronary heart disease risk for primary prevention requires consideration of the number needed to be treated to prevent one coronary heart disease event, the proportion of the population requiring treatment, the cost-effectiveness of treatment and the total cost of treatment. 2. In a random stratified sample of subjects aged 35-69 years from the Health Survey for England 1993 we first examined the prevalence of subjects with cardiovascular disease and serum cholesterol > 5.5 mmol/l who may be candidates for secondary prevention. In those free of cardiovascular disease we then examined the prevalence of subjects with serum cholesterol > 5.5 mmol/l who had three different levels of coronary heart disease risk: coronary heart disease event rates of 4.5% per year, 3.0% per year and 1.5% per year. These subjects may be candidates for primary prevention depending on the treatment policy selected. 3. For secondary prevention, 4.8% (95% confidence interval 4.3-5.3) of the U.K. population aged 35-69 years might be candidates for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor treatment, comprising 2.4% (2.0 to 2.7) with a history of myocardial infarction, 1.9% (1.6 to 2.2) with angina and 0.5% (0.3-0.7) with a history of stroke--all with total cholesterol > 5.5 mmol/l. The prevalence of these diagnoses with total cholesterol > 5.5 mmol/l increased with age, from 1.5% at age 35-39 years to 16.2% at age 65-69 years in men, and from 0.2% at age 35-39 years to 10.0% at age 65-69 years in women. Approximately 13 people would need treatment for 5 years to prevent one coronary event, at a cost of 36,000 pounds per event prevented. The number needing treatment for secondary prevention would increase substantially if treatment was extended to patients above 70 years of age or to those with serum cholesterol < or = 5.5 mmol/l. 4. Primary prevention aimed at a coronary event risk of 4.5% per year would lead to treatment of only 0.3% (0.2-0.4) of those aged 35-69 years, and those treated would be predominantly older men with additional risk factors for coronary heart disease. The number needed to be treated and cost per coronary event prevented would be similar to those for secondary prevention. 5. Primary prevention targeted at subjects with a coronary event rate of 3.0% per year would entail treating 3.4% (3.0-3.9) of all those aged 35-69 years. At this level of risk, 20 people would need treatment for 5 years to prevent one coronary event, at a cost of 55,000 pounds per event prevented. 6. Primary prevention aimed at a coronary event rate of 1.5% per year would entail treating 19.6% (18.7-20.6) of all subjects aged 35-69 years, and about 80% of men aged 60-69 years for primary or secondary prevention. At this level of risk, 40 people would need treatment for 5 years to prevent one event, at a cost of 111,000 pounds per event saved. 7. Guidelines for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor treatment should take into account the considerable workload and financial resources needed to implement secondary prevention of coronary heart disease, the accepted first priority. For primary prevention they need to consider the number needed to be treated to prevent one event, the number of subjects needing treatment, the cost-effectiveness of treatment and
 ...
PMID:Lipid-lowering for prevention of coronary heart disease: what policy now? 917 44

A meta-analysis of the benefits of coronary artery bypass graft (CABG) surgery has been used as the basis of a model for comparing the costs and benefits of surgical and medical treatment of angina pectoris. In order to allow for the results of recent research, the economic model included the addition of aspirin and aspirin plus an HMG-CoA reductase inhibitor (statin) to medical management. The analysis indicates that in unselected patients the cost-effectiveness of CABG vs initial standard medical therapy over 5 years is towards the upper limit of what can be considered a cost-effective treatment both in terms of its effect on mortality (life-years gained) and morbidity (quality adjusted life-years). Addition of a statin to medical therapy reduced mortality and made coronary artery bypass graft surgery an expensive option in terms of improvement of quality of life. In patients with three-vessel disease or left ventricular dysfunction surgery appears fairly cost-effective in comparison with standard medical therapy but becomes relatively expensive when the benefits of aspirin or lipid-lowering therapy are added to medical treatment.
 ...
PMID:Is medical treatment for angina the most cost-effective option? 915 68

Phagocytes play a major role in several diseases. In particular mononuclear phagocyte-derived foam cells have a prominent role in the development of the atherosclerotic lesions. Macrophages are present in all stages of atherogenesis; they internalize lipoproteins and accumulate cholesterol. Moreover, lipid-filled macrophages, by secreting extracellular matrix-degrading enzymes, may weaken rupture-prone atherosclerotic plaques, thus increasing the probability of precipitating atherosclerotic acute symptoms (i.e., myocardial infarction, angina, etc.). Therefore, control of cellular functions and cholesterol accumulation in macrophages represent pharmacological targets against atherosclerosis. In our laboratory we studied the effect of calcium antagonists on cellular cholesterol esterification in cultured macrophages. We also demonstrated that the HMG-CoA reductase inhibitors (vastatins) fluvastatin and simvastatin prevented cholesterol deposition in cultured human and murine macrophage by inhibiting modified LDL endocytosis. Interestingly, vastatin activity was more pronounced in cholesterol-loaded macrophages (i.e., foam cells) than in normal cells. In conclusion, in vitro pharmacological control of cholesterol accumulation in macrophages may be achieved with some calcium antagonists and vastatins independently of their effects on blood pressure or cholesterolemia.
 ...
PMID:Pharmacological control of phagocyte function: inhibition of cholesterol accumulation. 970 60

Recently guidelines for cholesterol lowering therapy by means of 'statines' (HMG-CoA reductase inhibitors) were published by the National Organization of Quality Assurance in Hospitals. The part about primary prevention of cardiovascular disease is based on absolute risks for coronary heart disease as calculated by the Framingham Heart Study risk functions and on a cost-effectiveness analysis. However, the function predicts risk of disease such as silent infarction and angina pectoris. The incidence thus produced is higher than any observed clinical incidence. Absolute risk increases exponentially with age, but remaining life expectancy, and thus benefit, decreases. Therefore, decisions about treatment levels are based on arbitrary assumptions. The function is ultimately only used to advise treatment to the smoker, while the better choice is always to stop smoking. The effectiveness is overestimated by using a long time horizon of treatment of 25 years in the cost-effectiveness analysis. Primary prevention of coronary heart disease according to the new guidelines is still very expensive.
 ...
PMID:[Primary prevention remains expensive, notwithstanding the consensus on lowering serum cholesterol levels]. 1034 37

Fifteen patients with either angina pectoris or old myocardial infarction, who had positive 201Tl single photon emission computed tomography (SPECT) imaging and coronary sclerosis of more than 50%, were treated with an HMG-CoA reductase inhibitor (simvastatin) for more than 1 year. They were compared with an untreated control group (n = 25). Total cholesterol decreased 22% and high-density lipoprotein (HDL) increased 9% with simvastatin; both changes were significantly different from those in controls. Long-term simvastatin induced improvement of myocardial perfusion on 201Tl SPECT images both during exercise and at rest, which was also significantly different from controls. In addition, the improvement of myocardial perfusion on 201Tl SPECT images was clearly related to the improvements in cholesterol values, especially nonHDL cholesterol. Thus, the greater the decrease in nonHDL cholesterol, the greater the improvement in myocardial perfusion at rest or during exercise with long-term treatment using an HMG-CoA reductase inhibitor. These findings indicate that the improvements in cholesterol values caused by HMG-CoA reductase inhibitor therapy are related to improvements of myocardial perfusion seen on 201Tl SPECT images.
 ...
PMID:Effect of long-term cholesterol-lowering treatment with HMG-CoA reductase inhibitor (simvastatin) on myocardial perfusion evaluated by thallium-201 single photon emission computed tomography. 1073 48

The aim of this review of the landmark HMG-CoA reductase inhibitors (statins) studies is to enable the clinician to draw practical lessons from these trials. The Scandinavian Simvastatin Survival Study (4S) established the importance of treating the hypercholesterolemic patient with established cardiovascular heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS) showed the benefit of treating healthy hypercholesterolemic men who were nevertheless at high risk of developing cardiovascular heart disease in the future. The Cholesterol and Recurrent Events (CARE) study, a secondary prevention trial, proved the benefit of treating patients with myocardial ischemia and cholesterol levels within normal limits. This conclusion was confirmed by the Long-term Intervention With Pravastatin in Ischemic Disease (LIPID) study, another secondary prevention study that enrolled patients with a wide range of cholesterol levels (4-7 mmol/dL), into which the large majority of patients would belong. The importance of treating patients with established ischemic heart disease (IHD), and those at high risk of developing cardiovascular heart disease, regardless of cholesterol level, was being realized. The Air Force/Texas Coronary Artery Prevention Study (AFCAPS/TexCAPS) then showed that treatment can reduce adverse cardiovascular events even in the primary prevention of patients with normal cholesterol levels. The Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) trial showed that hypocholesterolemic therapy is useful in the setting of an acute coronary syndrome, while the Atorvastatin Versus Revascularisation Treatment (AVERT) study showed that aggressive statin therapy is as good as angioplasty in reducing ischemic cardiac events in patients with stable angina pectoris. Finally, the Heart Protection Study (HPS) randomized more than 20,000 patients, and the value of statins in reducing adverse cardiovascular events in the high-risk patient, including the elderly, women, and even in those with low cholesterol levels, is beyond doubt. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not be dependent on the actual cholesterol level of the patient. It is interesting to compare the large amount of data on the value and safety of the statins with the much more limited and less convincing data on antioxidant vitamins.
 ...
PMID:Protecting the heart: a practical review of the statin studies. 1281 99

The designation of atherosclerosis as a chronic inflammatory process represents an interesting paradigmatic shift for cardiologists. The plasma concentrations of interleukin-6 and its hepatic byproduct, C-reactive protein, may reflect the intensity of occult plaque inflammation and the vulnerability to rupture. Monocyte chemoattractant protein-1 and interleukin-8 play a crucial role in initiating atherosclerosis by recruiting monocytes/macrophages to the vessel wall, which promotes atherosclerotic lesions and plaque vulnerability. In addition, circulating levels of these proinflammatory cytokines increase in patients with acute myocardial infarction and unstable angina, but not in those with stable angina. Also, the plasma concentrations of these cytokines increase after percutaneous coronary intervention, causing late restenosis after the procedure. Angiotensin II and other atherogenic factors induce these cytokines in the cardiovascular tissues through the activation of transcription factors, such as nuclear factor-kappaB or peroxisome proliferator-activated receptors. Conversely, HMG-CoA reductase inhibitors (statins) can potently inhibit these proinflammatory factors in the vessels. A small GTP-binding protein, Rho, may be a key molecule to explain the anti-inflammatory effects of statins. Interleukin-10 also exerts anti-inflammatory effects on the cardiovascular tissues, possibly by deactivating proinflammatory cytokines and inducible nitric oxide synthase. Gene therapy using interleukin-10 may be a promising means for untreatable or complicated cases of cardiovascular diseases. Thus, therapeutic modulations of these inflammatory cytokines may be useful in the prevention of atherosclerosis and future cardiovascular events.
 ...
PMID:Inflammatory cytokines and cardiovascular disease. 1456 Nov 60

Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice.
 ...
PMID:Interactions between grapefruit juice and cardiovascular drugs. 1544 71

When managing the risk factors of coronary heart diseases, therapies using drugs play an important role. This present study analyses self-reported data on current drug usage of men and women with coronary heart disease. The data were collected as a part of a wider drug utilisation survey which in turn is a module of the German National Health Interview and Examination Survey 1998 (Bundes-Gesundheitssurvey 1998). This survey was compiled by conducting a standardised computer-assisted medical interview with a representative sample of the German population between the ages of 18 and 79 years. Of the 7099 participants, 209 of the women and 252 of the men affirmed having had a medically diagnosed coronary heart disease (CHD) such as angina pectoris and/ or myocardial infarction. Slightly more men (87.3%) were using drugs to treat CHDs than the women (86.1%). They (the men) also used more drugs on average (men 3.3, women 3.0). These differences however were not statistically significant. Clear and statistically significant differences were present in the usage of salicylic acid (men 54.4%, women 45.6%), HMG CoA reductase inhibitors (men 26%, women 15.3%) and cardiac glycosides (men 14%, women 25.8%). The higher usage prevalence rate of salicylic acid found in the men still remained after taking their age, social status and the region (east vs west) into account. The differences in the usage of specific drugs in the treatment of CHDs in men and women indicate a difference in prescription behaviour in the ambulatory medical care. Whether and to which extent gender-specific differences still remain today has to be decided by using current epidemiological data representative of the population.
 ...
PMID:[Drug usage of men and women with coronary heart disease. Results of the German Federal Health Survey 1998]. 1554 98


1 2 Next >>