User login
Patients with acute MI should be transferred for angioplasty
Angioplasty within 2 hours of presentation for acute myocardial infarction (MI) is superior to thrombolysis, primarily due to a lower reinfarction rate. This is true whether a patient presents to a healthcare facility with angioplasty capability or one that transfers a patient.
Angioplasty within 2 hours of presentation for acute myocardial infarction (MI) is superior to thrombolysis, primarily due to a lower reinfarction rate. This is true whether a patient presents to a healthcare facility with angioplasty capability or one that transfers a patient.
Angioplasty within 2 hours of presentation for acute myocardial infarction (MI) is superior to thrombolysis, primarily due to a lower reinfarction rate. This is true whether a patient presents to a healthcare facility with angioplasty capability or one that transfers a patient.
Thrombolytic therapy for acute ischemic stroke: risks vs benefits
The evidence is not strong enough to recommend routine use of recombinant tissue plasminogen activator (rtPA) in the setting of acute ischemic stroke.
Although independence in activities of daily living 3 to 6 months later is better in those who receive rtPA, acute adverse events (including fatal intracranial hemorrhage) also significantly increase. Given the potentially fatal risks and heterogeneity of results among trials, thrombolytic therapy in the setting of acute ischemic stroke needs more investigation. In the future, we may be able to define a more specific group of patients for whom the potential benefits clearly outweigh the risks.
The evidence is not strong enough to recommend routine use of recombinant tissue plasminogen activator (rtPA) in the setting of acute ischemic stroke.
Although independence in activities of daily living 3 to 6 months later is better in those who receive rtPA, acute adverse events (including fatal intracranial hemorrhage) also significantly increase. Given the potentially fatal risks and heterogeneity of results among trials, thrombolytic therapy in the setting of acute ischemic stroke needs more investigation. In the future, we may be able to define a more specific group of patients for whom the potential benefits clearly outweigh the risks.
The evidence is not strong enough to recommend routine use of recombinant tissue plasminogen activator (rtPA) in the setting of acute ischemic stroke.
Although independence in activities of daily living 3 to 6 months later is better in those who receive rtPA, acute adverse events (including fatal intracranial hemorrhage) also significantly increase. Given the potentially fatal risks and heterogeneity of results among trials, thrombolytic therapy in the setting of acute ischemic stroke needs more investigation. In the future, we may be able to define a more specific group of patients for whom the potential benefits clearly outweigh the risks.
What is a reasonable interval for retinopathy screening in patients with diabetes?
Assuming that a given patient is reliable for follow-up and that a clinical system is in place to handle a more individualized screening protocol, the investigators suggest the following approach: 3-year intervals for patients with no retinopathy and no risk factors (risk factors being diabetes for longer than 20 years or use of insulin); annual screening for patients with no retinopathy and 1 or both risk factors or for patients with background retinopathy; and 4-month intervals for patients with mild preproliferative retinopathy.
These intervals provide at least a 95% probability of remaining free of sight-threatening diabetic retinopathy between screenings.
Assuming that a given patient is reliable for follow-up and that a clinical system is in place to handle a more individualized screening protocol, the investigators suggest the following approach: 3-year intervals for patients with no retinopathy and no risk factors (risk factors being diabetes for longer than 20 years or use of insulin); annual screening for patients with no retinopathy and 1 or both risk factors or for patients with background retinopathy; and 4-month intervals for patients with mild preproliferative retinopathy.
These intervals provide at least a 95% probability of remaining free of sight-threatening diabetic retinopathy between screenings.
Assuming that a given patient is reliable for follow-up and that a clinical system is in place to handle a more individualized screening protocol, the investigators suggest the following approach: 3-year intervals for patients with no retinopathy and no risk factors (risk factors being diabetes for longer than 20 years or use of insulin); annual screening for patients with no retinopathy and 1 or both risk factors or for patients with background retinopathy; and 4-month intervals for patients with mild preproliferative retinopathy.
These intervals provide at least a 95% probability of remaining free of sight-threatening diabetic retinopathy between screenings.
Ultrasonography helpful in diagnosing developmental hip dysplasia
Ultrasonography for diagnosis and management of possible hip instability may lead to less splinting and surgery in the first 2 years of life, with no significant difference in radiographic abnormalities. Cost-effectiveness, long-term hip mobility, and consistency of ultrasound interpretation is not proven.
Ultrasonography for diagnosis and management of possible hip instability may lead to less splinting and surgery in the first 2 years of life, with no significant difference in radiographic abnormalities. Cost-effectiveness, long-term hip mobility, and consistency of ultrasound interpretation is not proven.
Ultrasonography for diagnosis and management of possible hip instability may lead to less splinting and surgery in the first 2 years of life, with no significant difference in radiographic abnormalities. Cost-effectiveness, long-term hip mobility, and consistency of ultrasound interpretation is not proven.
The Journal of Family Practice ©2003 Dowden Health Media
Do the risks of estrogen plus progestin outweigh the benefits in healthy post-menopausal women?
ABSTRACT
BACKGROUND: One of the proposed benefits of postmenopausal hormone replacement therapy (HRT) is the prevention of coronary heart disease. This proposal is based on evidence from nonrandomized observational studies and intermediate outcomes such as improved lipid profiles. The possibility of harm from HRT has also been reported, particularly regarding breast cancer and thromboembolic disease. The Heart and Estrogen/progestin Replacement Study recently challenged the benefits of HRT, showing no overall protective effect on coronary heart disease (and an increased risk of harm in the first year of treatment) for women with prior coronary heart disease.
POPULATION STUDIED: The Women’s Health Initiative is a set of clinical trials with more than 160,000 women enrolled in studies of low-fat diet, calcium and vitamin D supplementation, and post-menopausal hormone use. This particular report focused on the trial of estrogen plus progestin in women with an intact uterus. A total of 16,608 post-menopausal women were randomized to receive either 1 daily tablet of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg (Prempro) or placebo. Women were excluded if they had a history of breast cancer, other cancer within 10 years, hysterectomy, anemia, thrombocytopenia, alcoholism, or dementia. Ages ranged from 50 to 79 years (mean 63 years). Approximately 36% of the women were being treated for hypertension, 4.4% had diabetes, and 7.7% reported a history of cardiovascular disease.
STUDY DESIGN AND VALIDITY: This was a well-designed double-blind, randomized controlled trial with concealed allocation. Baseline characteristics were similar between groups. Follow-up was conducted 6 weeks after randomization, every 6 months with questionnaires, and annually with in-clinic visits. Intention-to-treat analysis was appropriate and would tend to find smaller differences between groups given the high dropout rates (42% in the HRT group and 38% in the placebo group). The trial was originally designed to last more than 8 years, but the independent safety monitoring board recommended stopping the trial when the difference in breast cancer rates exceeded a predetermined threshold and the global index was supportive of harm. When the trial was stopped in the spring of 2002, the average follow-up period was 5.2 years.
OUTCOMES MEASURED: The primary outcome measure was the rate of coronary heart disease, defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction determined from serial electrocardiograms, or coronary heart disease death. The secondary outcome measure was hip fracture rate. The primary adverse outcome measure was invasive breast cancer rate. Reported outcomes also included other cancers, total fractures, stroke, pulmonary embolism, deep vein thrombosis, and total mortality. A global index of outcomes was also calculated as a summary measure of risks and benefits. No measures of vasomotor symptoms or quality of life were reported.
RESULTS: Women in the HRT group had a higher annual incidence of coronary heart disease (0.37% vs 0.30%, NNH = 1429), invasive breast cancer (0.38% vs 0.30%, NNH = 1250), stroke (0.29% vs 0.21%, NNH = 1250), and venous thromboembolic disease (0.34% vs 0.16%, NNH = 556). Bone fractures were less prevalent in the HRT group (total annual fracture rate, 1.47% vs 1.91%, NNT = 228), as was colorectal cancer (0.10% vs 0.16%, NNT = 1667). All of these differences except thromboembolic disease lost statistical significance when adjusting for multiple comparisons, but subgroup analyses showed these differences in adverse events regardless of baseline risks of coronary heart disease and breast cancer. Individuals who adhered to the study medication showed greater differences in adverse events, and individuals who had already used HRT before the study had higher rates of breast cancer. Overall mortality was not different in the 2 groups. The excess risk of events in the global index was 19 per 10,000 person-years. In other words, an average of 1 additional adverse event would be expected over 5 years of treatment for every 100 women meeting these criteria.
Combined HRT with estrogen plus progestin should not be used for prevention of coronary heart disease, and other agents should be considered for the prevention and treatment of osteoporosis. HRT may still be a reasonable option for perimenopausal, otherwise healthy women with significant vasomotor symptoms, provided they are informed of a slightly increased risk of adverse events. Use of HRT in these women should be limited if possible to 5 years or less. Ongoing questions include the potential benefit of estrogen alone in women without a uterus (that trial is ongoing) as well as the risks and benefits of other forms of estrogen and progestin.
ABSTRACT
BACKGROUND: One of the proposed benefits of postmenopausal hormone replacement therapy (HRT) is the prevention of coronary heart disease. This proposal is based on evidence from nonrandomized observational studies and intermediate outcomes such as improved lipid profiles. The possibility of harm from HRT has also been reported, particularly regarding breast cancer and thromboembolic disease. The Heart and Estrogen/progestin Replacement Study recently challenged the benefits of HRT, showing no overall protective effect on coronary heart disease (and an increased risk of harm in the first year of treatment) for women with prior coronary heart disease.
POPULATION STUDIED: The Women’s Health Initiative is a set of clinical trials with more than 160,000 women enrolled in studies of low-fat diet, calcium and vitamin D supplementation, and post-menopausal hormone use. This particular report focused on the trial of estrogen plus progestin in women with an intact uterus. A total of 16,608 post-menopausal women were randomized to receive either 1 daily tablet of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg (Prempro) or placebo. Women were excluded if they had a history of breast cancer, other cancer within 10 years, hysterectomy, anemia, thrombocytopenia, alcoholism, or dementia. Ages ranged from 50 to 79 years (mean 63 years). Approximately 36% of the women were being treated for hypertension, 4.4% had diabetes, and 7.7% reported a history of cardiovascular disease.
STUDY DESIGN AND VALIDITY: This was a well-designed double-blind, randomized controlled trial with concealed allocation. Baseline characteristics were similar between groups. Follow-up was conducted 6 weeks after randomization, every 6 months with questionnaires, and annually with in-clinic visits. Intention-to-treat analysis was appropriate and would tend to find smaller differences between groups given the high dropout rates (42% in the HRT group and 38% in the placebo group). The trial was originally designed to last more than 8 years, but the independent safety monitoring board recommended stopping the trial when the difference in breast cancer rates exceeded a predetermined threshold and the global index was supportive of harm. When the trial was stopped in the spring of 2002, the average follow-up period was 5.2 years.
OUTCOMES MEASURED: The primary outcome measure was the rate of coronary heart disease, defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction determined from serial electrocardiograms, or coronary heart disease death. The secondary outcome measure was hip fracture rate. The primary adverse outcome measure was invasive breast cancer rate. Reported outcomes also included other cancers, total fractures, stroke, pulmonary embolism, deep vein thrombosis, and total mortality. A global index of outcomes was also calculated as a summary measure of risks and benefits. No measures of vasomotor symptoms or quality of life were reported.
RESULTS: Women in the HRT group had a higher annual incidence of coronary heart disease (0.37% vs 0.30%, NNH = 1429), invasive breast cancer (0.38% vs 0.30%, NNH = 1250), stroke (0.29% vs 0.21%, NNH = 1250), and venous thromboembolic disease (0.34% vs 0.16%, NNH = 556). Bone fractures were less prevalent in the HRT group (total annual fracture rate, 1.47% vs 1.91%, NNT = 228), as was colorectal cancer (0.10% vs 0.16%, NNT = 1667). All of these differences except thromboembolic disease lost statistical significance when adjusting for multiple comparisons, but subgroup analyses showed these differences in adverse events regardless of baseline risks of coronary heart disease and breast cancer. Individuals who adhered to the study medication showed greater differences in adverse events, and individuals who had already used HRT before the study had higher rates of breast cancer. Overall mortality was not different in the 2 groups. The excess risk of events in the global index was 19 per 10,000 person-years. In other words, an average of 1 additional adverse event would be expected over 5 years of treatment for every 100 women meeting these criteria.
Combined HRT with estrogen plus progestin should not be used for prevention of coronary heart disease, and other agents should be considered for the prevention and treatment of osteoporosis. HRT may still be a reasonable option for perimenopausal, otherwise healthy women with significant vasomotor symptoms, provided they are informed of a slightly increased risk of adverse events. Use of HRT in these women should be limited if possible to 5 years or less. Ongoing questions include the potential benefit of estrogen alone in women without a uterus (that trial is ongoing) as well as the risks and benefits of other forms of estrogen and progestin.
ABSTRACT
BACKGROUND: One of the proposed benefits of postmenopausal hormone replacement therapy (HRT) is the prevention of coronary heart disease. This proposal is based on evidence from nonrandomized observational studies and intermediate outcomes such as improved lipid profiles. The possibility of harm from HRT has also been reported, particularly regarding breast cancer and thromboembolic disease. The Heart and Estrogen/progestin Replacement Study recently challenged the benefits of HRT, showing no overall protective effect on coronary heart disease (and an increased risk of harm in the first year of treatment) for women with prior coronary heart disease.
POPULATION STUDIED: The Women’s Health Initiative is a set of clinical trials with more than 160,000 women enrolled in studies of low-fat diet, calcium and vitamin D supplementation, and post-menopausal hormone use. This particular report focused on the trial of estrogen plus progestin in women with an intact uterus. A total of 16,608 post-menopausal women were randomized to receive either 1 daily tablet of conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg (Prempro) or placebo. Women were excluded if they had a history of breast cancer, other cancer within 10 years, hysterectomy, anemia, thrombocytopenia, alcoholism, or dementia. Ages ranged from 50 to 79 years (mean 63 years). Approximately 36% of the women were being treated for hypertension, 4.4% had diabetes, and 7.7% reported a history of cardiovascular disease.
STUDY DESIGN AND VALIDITY: This was a well-designed double-blind, randomized controlled trial with concealed allocation. Baseline characteristics were similar between groups. Follow-up was conducted 6 weeks after randomization, every 6 months with questionnaires, and annually with in-clinic visits. Intention-to-treat analysis was appropriate and would tend to find smaller differences between groups given the high dropout rates (42% in the HRT group and 38% in the placebo group). The trial was originally designed to last more than 8 years, but the independent safety monitoring board recommended stopping the trial when the difference in breast cancer rates exceeded a predetermined threshold and the global index was supportive of harm. When the trial was stopped in the spring of 2002, the average follow-up period was 5.2 years.
OUTCOMES MEASURED: The primary outcome measure was the rate of coronary heart disease, defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction determined from serial electrocardiograms, or coronary heart disease death. The secondary outcome measure was hip fracture rate. The primary adverse outcome measure was invasive breast cancer rate. Reported outcomes also included other cancers, total fractures, stroke, pulmonary embolism, deep vein thrombosis, and total mortality. A global index of outcomes was also calculated as a summary measure of risks and benefits. No measures of vasomotor symptoms or quality of life were reported.
RESULTS: Women in the HRT group had a higher annual incidence of coronary heart disease (0.37% vs 0.30%, NNH = 1429), invasive breast cancer (0.38% vs 0.30%, NNH = 1250), stroke (0.29% vs 0.21%, NNH = 1250), and venous thromboembolic disease (0.34% vs 0.16%, NNH = 556). Bone fractures were less prevalent in the HRT group (total annual fracture rate, 1.47% vs 1.91%, NNT = 228), as was colorectal cancer (0.10% vs 0.16%, NNT = 1667). All of these differences except thromboembolic disease lost statistical significance when adjusting for multiple comparisons, but subgroup analyses showed these differences in adverse events regardless of baseline risks of coronary heart disease and breast cancer. Individuals who adhered to the study medication showed greater differences in adverse events, and individuals who had already used HRT before the study had higher rates of breast cancer. Overall mortality was not different in the 2 groups. The excess risk of events in the global index was 19 per 10,000 person-years. In other words, an average of 1 additional adverse event would be expected over 5 years of treatment for every 100 women meeting these criteria.
Combined HRT with estrogen plus progestin should not be used for prevention of coronary heart disease, and other agents should be considered for the prevention and treatment of osteoporosis. HRT may still be a reasonable option for perimenopausal, otherwise healthy women with significant vasomotor symptoms, provided they are informed of a slightly increased risk of adverse events. Use of HRT in these women should be limited if possible to 5 years or less. Ongoing questions include the potential benefit of estrogen alone in women without a uterus (that trial is ongoing) as well as the risks and benefits of other forms of estrogen and progestin.
Cost effectiveness of aspirin vs clopidogrel for secondary prevention of coronary heart disease
ABSTRACT
BACKGROUND: Clopidogrel is a platelet aggregation inhibitor that is slightly more effective than aspirin in reducing the risk of cardiovascular events in individuals with preexisting cardiovascular disease (0.51% annual absolute risk reduction; Lancet 1996; 348:1329–39). However, clopidogrel is currently 80 times more expensive than aspirin. The authors looked at the risks, benefits, and costs of long-term use of various therapeutic strategies involving these 2 medications.
POPULATION STUDIED: A computer simulation, known as the Coronary Heart Disease Policy Model, was used to predict the number of patients in the United States (35–84 years) who would develop coronary disease before or during the next 25 years, as well as the number of subsequent cardiovascular events and deaths these individuals would experience. Only patients predicted to survive their first month after a cardiac event were included in the therapeutic intervention analysis. Parameters for the model were based on cohort studies and clinical trials found in the medical literature.
STUDY DESIGN AND VALIDITY: Beginning with their estimated number of Americans with coronary disease and cardiovascular events, the authors predicted the reduction in events using aspirin, clopidogrel, or both. The 4 possible treatment strategies were (1) aspirin 325 mg/day for all eligible patients; (2) aspirin for all eligible patients or clopidogrel 75 mg/day for the remaining 5.7% ineligible for aspirin; (3) clopidogrel 75 mg/day for all patients; or (4) a combination of clopidogrel for all patients plus aspirin for all eligible patients. They also considered costs of various interventions, including hospitalizations, rehabilitation services, outpatient and home services, and treatment for adverse drug effects such as gastrointestinal bleeding. To carry out the cost-effectiveness analysis over such a long time period, the authors discounted costs at a rate of 3% per year (a typical amount) and converted all values to year-2000 US dollars. Sensitivity analysis used upper and lower bounds of reductions from past trial data to give a reasonable range of values. As with all hypothetical cost-effectiveness studies, this study only represents the authors’ best estimates of costs and benefits, not actual results from a therapeutic trial or cohort. Issues such as the safety of combination therapy over this prolonged time period have not been well established.
OUTCOMES MEASURED: The main outcome was the cost per quality-adjusted life year (QALY) gained, that is, the cost of an additional year of optimal health.
RESULTS: Aspirin alone in all eligible patients (strategy #1) resulted in an estimated $11,000 per QALY gained. Giving clopidogrel to the 5.7% of patients ineligible for aspirin (strategy #2) would prevent some subsequent events at an increased cost, resulting in a total estimate of $31,000 per QALY gained compared with the first strategy. Using clopidogrel alone for everyone (strategy #3) led to a very high estimated cost of $250,000 per QALY gained compared with strategy #2. Combination therapy of clopidogrel for everyone plus aspirin for the 96.3% of eligible patients (strategy #4) resulted in an estimated cost of $130,000 per QALY gained compared with strategy #2. However, in patients with annual risks 3 times as high as that of the average patient with coronary disease, this ratio fell below $64,000 per QALY gained.
Considered from a societal standpoint, clopidogrel at its current price has acceptable cost effectiveness when used by patients with cardiovascular disease who cannot take aspirin. If the cost of clopidogrel falls substantially in the future, combination therapy with both clopidogrel and aspirin in these patients may also be a reasonable public health policy.
ABSTRACT
BACKGROUND: Clopidogrel is a platelet aggregation inhibitor that is slightly more effective than aspirin in reducing the risk of cardiovascular events in individuals with preexisting cardiovascular disease (0.51% annual absolute risk reduction; Lancet 1996; 348:1329–39). However, clopidogrel is currently 80 times more expensive than aspirin. The authors looked at the risks, benefits, and costs of long-term use of various therapeutic strategies involving these 2 medications.
POPULATION STUDIED: A computer simulation, known as the Coronary Heart Disease Policy Model, was used to predict the number of patients in the United States (35–84 years) who would develop coronary disease before or during the next 25 years, as well as the number of subsequent cardiovascular events and deaths these individuals would experience. Only patients predicted to survive their first month after a cardiac event were included in the therapeutic intervention analysis. Parameters for the model were based on cohort studies and clinical trials found in the medical literature.
STUDY DESIGN AND VALIDITY: Beginning with their estimated number of Americans with coronary disease and cardiovascular events, the authors predicted the reduction in events using aspirin, clopidogrel, or both. The 4 possible treatment strategies were (1) aspirin 325 mg/day for all eligible patients; (2) aspirin for all eligible patients or clopidogrel 75 mg/day for the remaining 5.7% ineligible for aspirin; (3) clopidogrel 75 mg/day for all patients; or (4) a combination of clopidogrel for all patients plus aspirin for all eligible patients. They also considered costs of various interventions, including hospitalizations, rehabilitation services, outpatient and home services, and treatment for adverse drug effects such as gastrointestinal bleeding. To carry out the cost-effectiveness analysis over such a long time period, the authors discounted costs at a rate of 3% per year (a typical amount) and converted all values to year-2000 US dollars. Sensitivity analysis used upper and lower bounds of reductions from past trial data to give a reasonable range of values. As with all hypothetical cost-effectiveness studies, this study only represents the authors’ best estimates of costs and benefits, not actual results from a therapeutic trial or cohort. Issues such as the safety of combination therapy over this prolonged time period have not been well established.
OUTCOMES MEASURED: The main outcome was the cost per quality-adjusted life year (QALY) gained, that is, the cost of an additional year of optimal health.
RESULTS: Aspirin alone in all eligible patients (strategy #1) resulted in an estimated $11,000 per QALY gained. Giving clopidogrel to the 5.7% of patients ineligible for aspirin (strategy #2) would prevent some subsequent events at an increased cost, resulting in a total estimate of $31,000 per QALY gained compared with the first strategy. Using clopidogrel alone for everyone (strategy #3) led to a very high estimated cost of $250,000 per QALY gained compared with strategy #2. Combination therapy of clopidogrel for everyone plus aspirin for the 96.3% of eligible patients (strategy #4) resulted in an estimated cost of $130,000 per QALY gained compared with strategy #2. However, in patients with annual risks 3 times as high as that of the average patient with coronary disease, this ratio fell below $64,000 per QALY gained.
Considered from a societal standpoint, clopidogrel at its current price has acceptable cost effectiveness when used by patients with cardiovascular disease who cannot take aspirin. If the cost of clopidogrel falls substantially in the future, combination therapy with both clopidogrel and aspirin in these patients may also be a reasonable public health policy.
ABSTRACT
BACKGROUND: Clopidogrel is a platelet aggregation inhibitor that is slightly more effective than aspirin in reducing the risk of cardiovascular events in individuals with preexisting cardiovascular disease (0.51% annual absolute risk reduction; Lancet 1996; 348:1329–39). However, clopidogrel is currently 80 times more expensive than aspirin. The authors looked at the risks, benefits, and costs of long-term use of various therapeutic strategies involving these 2 medications.
POPULATION STUDIED: A computer simulation, known as the Coronary Heart Disease Policy Model, was used to predict the number of patients in the United States (35–84 years) who would develop coronary disease before or during the next 25 years, as well as the number of subsequent cardiovascular events and deaths these individuals would experience. Only patients predicted to survive their first month after a cardiac event were included in the therapeutic intervention analysis. Parameters for the model were based on cohort studies and clinical trials found in the medical literature.
STUDY DESIGN AND VALIDITY: Beginning with their estimated number of Americans with coronary disease and cardiovascular events, the authors predicted the reduction in events using aspirin, clopidogrel, or both. The 4 possible treatment strategies were (1) aspirin 325 mg/day for all eligible patients; (2) aspirin for all eligible patients or clopidogrel 75 mg/day for the remaining 5.7% ineligible for aspirin; (3) clopidogrel 75 mg/day for all patients; or (4) a combination of clopidogrel for all patients plus aspirin for all eligible patients. They also considered costs of various interventions, including hospitalizations, rehabilitation services, outpatient and home services, and treatment for adverse drug effects such as gastrointestinal bleeding. To carry out the cost-effectiveness analysis over such a long time period, the authors discounted costs at a rate of 3% per year (a typical amount) and converted all values to year-2000 US dollars. Sensitivity analysis used upper and lower bounds of reductions from past trial data to give a reasonable range of values. As with all hypothetical cost-effectiveness studies, this study only represents the authors’ best estimates of costs and benefits, not actual results from a therapeutic trial or cohort. Issues such as the safety of combination therapy over this prolonged time period have not been well established.
OUTCOMES MEASURED: The main outcome was the cost per quality-adjusted life year (QALY) gained, that is, the cost of an additional year of optimal health.
RESULTS: Aspirin alone in all eligible patients (strategy #1) resulted in an estimated $11,000 per QALY gained. Giving clopidogrel to the 5.7% of patients ineligible for aspirin (strategy #2) would prevent some subsequent events at an increased cost, resulting in a total estimate of $31,000 per QALY gained compared with the first strategy. Using clopidogrel alone for everyone (strategy #3) led to a very high estimated cost of $250,000 per QALY gained compared with strategy #2. Combination therapy of clopidogrel for everyone plus aspirin for the 96.3% of eligible patients (strategy #4) resulted in an estimated cost of $130,000 per QALY gained compared with strategy #2. However, in patients with annual risks 3 times as high as that of the average patient with coronary disease, this ratio fell below $64,000 per QALY gained.
Considered from a societal standpoint, clopidogrel at its current price has acceptable cost effectiveness when used by patients with cardiovascular disease who cannot take aspirin. If the cost of clopidogrel falls substantially in the future, combination therapy with both clopidogrel and aspirin in these patients may also be a reasonable public health policy.
When should patients with asymptomatic aortic stenosis be evaluated for valve replacement?
For patients whose echocardiograms show advanced calcification of the aortic valves, a jet velocity of > 4.0 m/s, or a progression in jet velocity of 0.3m/s/year; and for patients who have an abnormal exercise response or an impaired functional status, consider referral for valve replacement prior to the onset of symptoms (Grade of Recommendation: C).
Evidence summary
Aortic stenosis is a narrowing of the aortic valve. Degree of severity is judged by valve area: mild (1.5–2.0 cm2), moderate (1.0–1.5 cm2), severe (< 1.0 cm2). Alternatively, stenosis may be classified by transvalvular gradient or jet velocity, the latter being the easier quantity to measure by echocardiogram. Prevalence of aortic stenosis increases with age; one series of 1243 elderly women (mean age of 82) found mild stenosis in 10%, moderate stenosis in 6%, and severe stenosis in 2%.1 Natural history studies show that once classic symptoms develop, average survival decreases to 5 years with the onset of angina, 3 years after cardiac syncope, and 2 years after heart failure.2 The incidence of sudden death increases from < 1% annually among asymptomatic patients to 15% to 20% among symptomatic patients.3,4
Aortic stenosis is suggested by such findings as a harsh systolic murmur at the right upper sternal border, pulsus parvus et tardus, and a sustained point of maximal impulse. Exercise stress testing may provide additional information. In one prospective study of 123 patients, those who had a greater increase in valve area, cardiac output, and blood pressure and a smaller decrease in stroke volume on stress echocardiogram were more likely to remain asymptomatic for the entire length of their time in the study, an average of 2.5 years.5
Asymptomatic patients with aortic stenosis who undergo coronary artery bypass grafting (CABG) often have their aortic valve replaced at the same time; the timing of aortic valve replacement in patients not requiring CABG is controversial. One prospective study found the severity of stenosis at baseline to be the strongest prognostic predictor. Patients with a jet velocity of < 3.0 m/s were unlikely to develop symptoms within 5 years; those with a jet velocity of 4.0 m/s had a > 50% likelihood of developing symptoms or dying within 2 years.5 Another study followed 128 patients for 4 years and found that moderate to severe valvular calcification and an increase in jet velocity of 0.3 m/s/year were the best prognostic predictors.6 Almost 80% of those with both calcification and a rapid change in jet velocity underwent surgery or died within 2 years6 (Table).
TABLE
Indications for possible valve replacement with asymptomatic aortic stenosis
| Predicting factor | Marker of worse prognosis |
|---|---|
| Calcification | Moderate to severe (multiple large calcified areas to extensive calcification of all cusps) |
| Jet velocity | > 4.0 m/s |
| Rate of jet velocity progression | ≥0.3 m/s/year |
| Exercise response | Minimal to no change in valve area, cardiac output, and blood pressure; marked decrease in stroke volume |
| Functional status | Impaired initially or declining |
Recommendations from others
The American College of Cardiology/American Heart Association Task Force on Practice Guidelines recommends echocardiograms every 5 years for mild stenosis, every 2 years for moderate stenosis, and annually for severe stenosis.4 There is no guideline for exercise testing. Aortic valve replacement is recommended for symptomatic patients and patients with severe stenosis undergoing CABG or other valvular or aortic surgery.
Clinical Commentary by Ken Grauer, MD; and search strategy, at www.fpin.org.
1. Aronow WS, Ahn C, Kronzon I. Am J Cardiol 1997;79:379-80.
2. Ross J, Jr., Braunwald E. Circulation 1968;38(1 Suppl ):61-7.
3. Balentine J, Eisenhart A. Aortic Stenosis. EMedicine Journal 2002;3:1.-
4. Bonow RO, Carabello B, deLeon AC, Jr., et al. Circulation 1998;98:1949-84.
5. Otto CM, Burwash IG, Legget ME, et al. Circulation 1997;95:2262-70.
6. Rosenhek R, Binder T, Porenta G, et al. N Engl J Med 2000;343:611-7.
For patients whose echocardiograms show advanced calcification of the aortic valves, a jet velocity of > 4.0 m/s, or a progression in jet velocity of 0.3m/s/year; and for patients who have an abnormal exercise response or an impaired functional status, consider referral for valve replacement prior to the onset of symptoms (Grade of Recommendation: C).
Evidence summary
Aortic stenosis is a narrowing of the aortic valve. Degree of severity is judged by valve area: mild (1.5–2.0 cm2), moderate (1.0–1.5 cm2), severe (< 1.0 cm2). Alternatively, stenosis may be classified by transvalvular gradient or jet velocity, the latter being the easier quantity to measure by echocardiogram. Prevalence of aortic stenosis increases with age; one series of 1243 elderly women (mean age of 82) found mild stenosis in 10%, moderate stenosis in 6%, and severe stenosis in 2%.1 Natural history studies show that once classic symptoms develop, average survival decreases to 5 years with the onset of angina, 3 years after cardiac syncope, and 2 years after heart failure.2 The incidence of sudden death increases from < 1% annually among asymptomatic patients to 15% to 20% among symptomatic patients.3,4
Aortic stenosis is suggested by such findings as a harsh systolic murmur at the right upper sternal border, pulsus parvus et tardus, and a sustained point of maximal impulse. Exercise stress testing may provide additional information. In one prospective study of 123 patients, those who had a greater increase in valve area, cardiac output, and blood pressure and a smaller decrease in stroke volume on stress echocardiogram were more likely to remain asymptomatic for the entire length of their time in the study, an average of 2.5 years.5
Asymptomatic patients with aortic stenosis who undergo coronary artery bypass grafting (CABG) often have their aortic valve replaced at the same time; the timing of aortic valve replacement in patients not requiring CABG is controversial. One prospective study found the severity of stenosis at baseline to be the strongest prognostic predictor. Patients with a jet velocity of < 3.0 m/s were unlikely to develop symptoms within 5 years; those with a jet velocity of 4.0 m/s had a > 50% likelihood of developing symptoms or dying within 2 years.5 Another study followed 128 patients for 4 years and found that moderate to severe valvular calcification and an increase in jet velocity of 0.3 m/s/year were the best prognostic predictors.6 Almost 80% of those with both calcification and a rapid change in jet velocity underwent surgery or died within 2 years6 (Table).
TABLE
Indications for possible valve replacement with asymptomatic aortic stenosis
| Predicting factor | Marker of worse prognosis |
|---|---|
| Calcification | Moderate to severe (multiple large calcified areas to extensive calcification of all cusps) |
| Jet velocity | > 4.0 m/s |
| Rate of jet velocity progression | ≥0.3 m/s/year |
| Exercise response | Minimal to no change in valve area, cardiac output, and blood pressure; marked decrease in stroke volume |
| Functional status | Impaired initially or declining |
Recommendations from others
The American College of Cardiology/American Heart Association Task Force on Practice Guidelines recommends echocardiograms every 5 years for mild stenosis, every 2 years for moderate stenosis, and annually for severe stenosis.4 There is no guideline for exercise testing. Aortic valve replacement is recommended for symptomatic patients and patients with severe stenosis undergoing CABG or other valvular or aortic surgery.
Clinical Commentary by Ken Grauer, MD; and search strategy, at www.fpin.org.
For patients whose echocardiograms show advanced calcification of the aortic valves, a jet velocity of > 4.0 m/s, or a progression in jet velocity of 0.3m/s/year; and for patients who have an abnormal exercise response or an impaired functional status, consider referral for valve replacement prior to the onset of symptoms (Grade of Recommendation: C).
Evidence summary
Aortic stenosis is a narrowing of the aortic valve. Degree of severity is judged by valve area: mild (1.5–2.0 cm2), moderate (1.0–1.5 cm2), severe (< 1.0 cm2). Alternatively, stenosis may be classified by transvalvular gradient or jet velocity, the latter being the easier quantity to measure by echocardiogram. Prevalence of aortic stenosis increases with age; one series of 1243 elderly women (mean age of 82) found mild stenosis in 10%, moderate stenosis in 6%, and severe stenosis in 2%.1 Natural history studies show that once classic symptoms develop, average survival decreases to 5 years with the onset of angina, 3 years after cardiac syncope, and 2 years after heart failure.2 The incidence of sudden death increases from < 1% annually among asymptomatic patients to 15% to 20% among symptomatic patients.3,4
Aortic stenosis is suggested by such findings as a harsh systolic murmur at the right upper sternal border, pulsus parvus et tardus, and a sustained point of maximal impulse. Exercise stress testing may provide additional information. In one prospective study of 123 patients, those who had a greater increase in valve area, cardiac output, and blood pressure and a smaller decrease in stroke volume on stress echocardiogram were more likely to remain asymptomatic for the entire length of their time in the study, an average of 2.5 years.5
Asymptomatic patients with aortic stenosis who undergo coronary artery bypass grafting (CABG) often have their aortic valve replaced at the same time; the timing of aortic valve replacement in patients not requiring CABG is controversial. One prospective study found the severity of stenosis at baseline to be the strongest prognostic predictor. Patients with a jet velocity of < 3.0 m/s were unlikely to develop symptoms within 5 years; those with a jet velocity of 4.0 m/s had a > 50% likelihood of developing symptoms or dying within 2 years.5 Another study followed 128 patients for 4 years and found that moderate to severe valvular calcification and an increase in jet velocity of 0.3 m/s/year were the best prognostic predictors.6 Almost 80% of those with both calcification and a rapid change in jet velocity underwent surgery or died within 2 years6 (Table).
TABLE
Indications for possible valve replacement with asymptomatic aortic stenosis
| Predicting factor | Marker of worse prognosis |
|---|---|
| Calcification | Moderate to severe (multiple large calcified areas to extensive calcification of all cusps) |
| Jet velocity | > 4.0 m/s |
| Rate of jet velocity progression | ≥0.3 m/s/year |
| Exercise response | Minimal to no change in valve area, cardiac output, and blood pressure; marked decrease in stroke volume |
| Functional status | Impaired initially or declining |
Recommendations from others
The American College of Cardiology/American Heart Association Task Force on Practice Guidelines recommends echocardiograms every 5 years for mild stenosis, every 2 years for moderate stenosis, and annually for severe stenosis.4 There is no guideline for exercise testing. Aortic valve replacement is recommended for symptomatic patients and patients with severe stenosis undergoing CABG or other valvular or aortic surgery.
Clinical Commentary by Ken Grauer, MD; and search strategy, at www.fpin.org.
1. Aronow WS, Ahn C, Kronzon I. Am J Cardiol 1997;79:379-80.
2. Ross J, Jr., Braunwald E. Circulation 1968;38(1 Suppl ):61-7.
3. Balentine J, Eisenhart A. Aortic Stenosis. EMedicine Journal 2002;3:1.-
4. Bonow RO, Carabello B, deLeon AC, Jr., et al. Circulation 1998;98:1949-84.
5. Otto CM, Burwash IG, Legget ME, et al. Circulation 1997;95:2262-70.
6. Rosenhek R, Binder T, Porenta G, et al. N Engl J Med 2000;343:611-7.
1. Aronow WS, Ahn C, Kronzon I. Am J Cardiol 1997;79:379-80.
2. Ross J, Jr., Braunwald E. Circulation 1968;38(1 Suppl ):61-7.
3. Balentine J, Eisenhart A. Aortic Stenosis. EMedicine Journal 2002;3:1.-
4. Bonow RO, Carabello B, deLeon AC, Jr., et al. Circulation 1998;98:1949-84.
5. Otto CM, Burwash IG, Legget ME, et al. Circulation 1997;95:2262-70.
6. Rosenhek R, Binder T, Porenta G, et al. N Engl J Med 2000;343:611-7.
Evidence-based answers from the Family Physicians Inquiries Network
How accurate is the Canadian C-spine rule for the detection of clinically significant cervical spine injuries?
ABSTRACT
BACKGROUND: Current use of cervical spine (C-spine) radiography for alert and stable trauma patients is highly variable and expensive in practice. A recent clinical decision rule to identify low-risk patients was accurate in distinguishing those who would not need radiography (high sensitivity) but would result in many patients being unnecessarily imaged (low specificity).1 The originators of the Ottawa Ankle and Knee rules have created a decision rule for use of C-spine radiography.
POPULATION STUDIED: The study enrolled patients 16 years and older who sustained acute blunt trauma to the head or neck and presented to an emergency department (ED) of 10 large Canadian hospitals. Patients had to be completely alert with normal vital signs. They either had to report neck pain or be nonambulatory with visible injury above the clavicles after a dangerous mechanism of injury. Patients were not studied if they were injured more than 48 hours before presentation, were returning for reassessment of the same injury, were pregnant, or had penetrating trauma, acute paralysis, or known vertebral disease.
STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which physicians determined 20 standardized clinical findings from the history and physical examination. The physician would then decide whether to obtain C-spine radiography; if no X-ray was obtained, a structured telephone interview 14 days later determined whether a clinically important C-spine injury had taken place. Clinical findings were then analyzed for their association with significant C-spine injuries. Although the study attempted to enroll consecutive patients, 3281 of 12,782 eligible patients were not enrolled for unclear reasons, and 577 patients could not be contacted by telephone for follow-up.
OUTCOMES MEASURED: The primary outcome measure was clinically important C-spine injury, defined as a fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging.
RESULTS: Approximately 69% of patients underwent C-spine radiography, and 31% underwent the 14-day follow-up phone interview. A total of 151 (1.7%) were determined to have a clinically important C-spine injury. No patients who did not undergo radiography were found to have important injuries 14 days later.
The Canadian C-Spine rule shows promise as an aid to decide whether to use C-spine radiography in alert stable patients with head or neck injuries. It demonstrates high sensitivity and reasonable specificity. However, the rule needs to be validated in other populations before accepting it as the standard of care.
ABSTRACT
BACKGROUND: Current use of cervical spine (C-spine) radiography for alert and stable trauma patients is highly variable and expensive in practice. A recent clinical decision rule to identify low-risk patients was accurate in distinguishing those who would not need radiography (high sensitivity) but would result in many patients being unnecessarily imaged (low specificity).1 The originators of the Ottawa Ankle and Knee rules have created a decision rule for use of C-spine radiography.
POPULATION STUDIED: The study enrolled patients 16 years and older who sustained acute blunt trauma to the head or neck and presented to an emergency department (ED) of 10 large Canadian hospitals. Patients had to be completely alert with normal vital signs. They either had to report neck pain or be nonambulatory with visible injury above the clavicles after a dangerous mechanism of injury. Patients were not studied if they were injured more than 48 hours before presentation, were returning for reassessment of the same injury, were pregnant, or had penetrating trauma, acute paralysis, or known vertebral disease.
STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which physicians determined 20 standardized clinical findings from the history and physical examination. The physician would then decide whether to obtain C-spine radiography; if no X-ray was obtained, a structured telephone interview 14 days later determined whether a clinically important C-spine injury had taken place. Clinical findings were then analyzed for their association with significant C-spine injuries. Although the study attempted to enroll consecutive patients, 3281 of 12,782 eligible patients were not enrolled for unclear reasons, and 577 patients could not be contacted by telephone for follow-up.
OUTCOMES MEASURED: The primary outcome measure was clinically important C-spine injury, defined as a fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging.
RESULTS: Approximately 69% of patients underwent C-spine radiography, and 31% underwent the 14-day follow-up phone interview. A total of 151 (1.7%) were determined to have a clinically important C-spine injury. No patients who did not undergo radiography were found to have important injuries 14 days later.
The Canadian C-Spine rule shows promise as an aid to decide whether to use C-spine radiography in alert stable patients with head or neck injuries. It demonstrates high sensitivity and reasonable specificity. However, the rule needs to be validated in other populations before accepting it as the standard of care.
ABSTRACT
BACKGROUND: Current use of cervical spine (C-spine) radiography for alert and stable trauma patients is highly variable and expensive in practice. A recent clinical decision rule to identify low-risk patients was accurate in distinguishing those who would not need radiography (high sensitivity) but would result in many patients being unnecessarily imaged (low specificity).1 The originators of the Ottawa Ankle and Knee rules have created a decision rule for use of C-spine radiography.
POPULATION STUDIED: The study enrolled patients 16 years and older who sustained acute blunt trauma to the head or neck and presented to an emergency department (ED) of 10 large Canadian hospitals. Patients had to be completely alert with normal vital signs. They either had to report neck pain or be nonambulatory with visible injury above the clavicles after a dangerous mechanism of injury. Patients were not studied if they were injured more than 48 hours before presentation, were returning for reassessment of the same injury, were pregnant, or had penetrating trauma, acute paralysis, or known vertebral disease.
STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which physicians determined 20 standardized clinical findings from the history and physical examination. The physician would then decide whether to obtain C-spine radiography; if no X-ray was obtained, a structured telephone interview 14 days later determined whether a clinically important C-spine injury had taken place. Clinical findings were then analyzed for their association with significant C-spine injuries. Although the study attempted to enroll consecutive patients, 3281 of 12,782 eligible patients were not enrolled for unclear reasons, and 577 patients could not be contacted by telephone for follow-up.
OUTCOMES MEASURED: The primary outcome measure was clinically important C-spine injury, defined as a fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging.
RESULTS: Approximately 69% of patients underwent C-spine radiography, and 31% underwent the 14-day follow-up phone interview. A total of 151 (1.7%) were determined to have a clinically important C-spine injury. No patients who did not undergo radiography were found to have important injuries 14 days later.
The Canadian C-Spine rule shows promise as an aid to decide whether to use C-spine radiography in alert stable patients with head or neck injuries. It demonstrates high sensitivity and reasonable specificity. However, the rule needs to be validated in other populations before accepting it as the standard of care.
Do third-generation oral contraceptives (OCs) increase the risk of venous thrombosis?
BACKGROUND: In the middle of the last decade several studies suggested an increased risk of thromboembolic events in women using the newer generation of oral contraceptives (OCs). These pills contain the newer progestins desogestrel, gestodene, and norgestimate. The authors of this meta-analysis attempted to address possible confounders and biases in these past studies and quantify the strength of the association.
POPULATION STUDIED: The meta-analysis included 9 case-control studies involving 3417 cases of thromboembolic disease with 9600 controls, as well as 3 cohort studies of more than 1 million women. Reported ages ranged from 15 to 49 years. All but one study (with 471 cases and 1772 controls) reported exclusion of women with a previous history of thromboembolism. Settings included hospitals, primary care offices and specialty clinics, primarily in Europe. Only studies comparing third-generation OCs to second-generation OCs were included in the final analyses.
STUDY DESIGN AND VALIDITY: The selected cohort or case-control articles were required to define cases as women with venous thrombosis or thromboembolism, and they had to contain sufficient information to determine relative risk and confidence intervals. The data were all obtained before November 1995. The study addressed possible heterogeneity among studies by stratified analysis of the results.
OUTCOMES MEASURED: The main outcome was the onset of venous embolism, comparing third-generation OC users to second-generation OC users. Because no randomized trial data were available, the investigators used odds ratios as an approximation of relative risk.
RESULTS: The study arrived at an overall adjusted odds ratio of 1.7 (95% confidence interval [CI], 1.4-2.0), a 70% higher association with thromboembolism for third-generation OCs compared with second-generation OCs. The highest odds ratio, 3.1 (95% CI, 2.0-4.6), was among first-time users. For short-term users (less than 1 year) the odds ratio was 2.5 (95% CI, 1.6-4.1), compared with 2.0 (95% CI, 1.4-2.7) for use longer than 1 year. Studies funded by the pharmaceutical industry had an odds ratio of 1.3 (95% CI, 1.0-1.7), while independent studies had an odds ratio of 2.3 (95% CI, 1.7-3.2). Age and confirmation of thromboembolism by vascular studies did not affect the odds ratios. These numbers translate to 1.5 additional incidents of thromboembolic disease per 10,000 woman years, approximately 4 additional deaths per 1,000,000 woman years. In other words, 25,000 women have to be treated over 10 years with third-generation OCs instead of second-generation OCs to expect one additional death.
This meta-analysis shows an increased association of thromboembolic disease with third-generation OCs compared with second-generation pills. Despite this relative increase, the absolute incidence of additional disease remains small. These agents may be reserved as second-line options for women intolerant of more established OCs. Their increased risk pales in comparison with the risk of adverse events of unplanned pregnancies in the United States, including a thromboembolism rate of at least 6 events per 10,000 pregnancies1 and a maternal mortality rate of 75 deaths per million live births.2
BACKGROUND: In the middle of the last decade several studies suggested an increased risk of thromboembolic events in women using the newer generation of oral contraceptives (OCs). These pills contain the newer progestins desogestrel, gestodene, and norgestimate. The authors of this meta-analysis attempted to address possible confounders and biases in these past studies and quantify the strength of the association.
POPULATION STUDIED: The meta-analysis included 9 case-control studies involving 3417 cases of thromboembolic disease with 9600 controls, as well as 3 cohort studies of more than 1 million women. Reported ages ranged from 15 to 49 years. All but one study (with 471 cases and 1772 controls) reported exclusion of women with a previous history of thromboembolism. Settings included hospitals, primary care offices and specialty clinics, primarily in Europe. Only studies comparing third-generation OCs to second-generation OCs were included in the final analyses.
STUDY DESIGN AND VALIDITY: The selected cohort or case-control articles were required to define cases as women with venous thrombosis or thromboembolism, and they had to contain sufficient information to determine relative risk and confidence intervals. The data were all obtained before November 1995. The study addressed possible heterogeneity among studies by stratified analysis of the results.
OUTCOMES MEASURED: The main outcome was the onset of venous embolism, comparing third-generation OC users to second-generation OC users. Because no randomized trial data were available, the investigators used odds ratios as an approximation of relative risk.
RESULTS: The study arrived at an overall adjusted odds ratio of 1.7 (95% confidence interval [CI], 1.4-2.0), a 70% higher association with thromboembolism for third-generation OCs compared with second-generation OCs. The highest odds ratio, 3.1 (95% CI, 2.0-4.6), was among first-time users. For short-term users (less than 1 year) the odds ratio was 2.5 (95% CI, 1.6-4.1), compared with 2.0 (95% CI, 1.4-2.7) for use longer than 1 year. Studies funded by the pharmaceutical industry had an odds ratio of 1.3 (95% CI, 1.0-1.7), while independent studies had an odds ratio of 2.3 (95% CI, 1.7-3.2). Age and confirmation of thromboembolism by vascular studies did not affect the odds ratios. These numbers translate to 1.5 additional incidents of thromboembolic disease per 10,000 woman years, approximately 4 additional deaths per 1,000,000 woman years. In other words, 25,000 women have to be treated over 10 years with third-generation OCs instead of second-generation OCs to expect one additional death.
This meta-analysis shows an increased association of thromboembolic disease with third-generation OCs compared with second-generation pills. Despite this relative increase, the absolute incidence of additional disease remains small. These agents may be reserved as second-line options for women intolerant of more established OCs. Their increased risk pales in comparison with the risk of adverse events of unplanned pregnancies in the United States, including a thromboembolism rate of at least 6 events per 10,000 pregnancies1 and a maternal mortality rate of 75 deaths per million live births.2
BACKGROUND: In the middle of the last decade several studies suggested an increased risk of thromboembolic events in women using the newer generation of oral contraceptives (OCs). These pills contain the newer progestins desogestrel, gestodene, and norgestimate. The authors of this meta-analysis attempted to address possible confounders and biases in these past studies and quantify the strength of the association.
POPULATION STUDIED: The meta-analysis included 9 case-control studies involving 3417 cases of thromboembolic disease with 9600 controls, as well as 3 cohort studies of more than 1 million women. Reported ages ranged from 15 to 49 years. All but one study (with 471 cases and 1772 controls) reported exclusion of women with a previous history of thromboembolism. Settings included hospitals, primary care offices and specialty clinics, primarily in Europe. Only studies comparing third-generation OCs to second-generation OCs were included in the final analyses.
STUDY DESIGN AND VALIDITY: The selected cohort or case-control articles were required to define cases as women with venous thrombosis or thromboembolism, and they had to contain sufficient information to determine relative risk and confidence intervals. The data were all obtained before November 1995. The study addressed possible heterogeneity among studies by stratified analysis of the results.
OUTCOMES MEASURED: The main outcome was the onset of venous embolism, comparing third-generation OC users to second-generation OC users. Because no randomized trial data were available, the investigators used odds ratios as an approximation of relative risk.
RESULTS: The study arrived at an overall adjusted odds ratio of 1.7 (95% confidence interval [CI], 1.4-2.0), a 70% higher association with thromboembolism for third-generation OCs compared with second-generation OCs. The highest odds ratio, 3.1 (95% CI, 2.0-4.6), was among first-time users. For short-term users (less than 1 year) the odds ratio was 2.5 (95% CI, 1.6-4.1), compared with 2.0 (95% CI, 1.4-2.7) for use longer than 1 year. Studies funded by the pharmaceutical industry had an odds ratio of 1.3 (95% CI, 1.0-1.7), while independent studies had an odds ratio of 2.3 (95% CI, 1.7-3.2). Age and confirmation of thromboembolism by vascular studies did not affect the odds ratios. These numbers translate to 1.5 additional incidents of thromboembolic disease per 10,000 woman years, approximately 4 additional deaths per 1,000,000 woman years. In other words, 25,000 women have to be treated over 10 years with third-generation OCs instead of second-generation OCs to expect one additional death.
This meta-analysis shows an increased association of thromboembolic disease with third-generation OCs compared with second-generation pills. Despite this relative increase, the absolute incidence of additional disease remains small. These agents may be reserved as second-line options for women intolerant of more established OCs. Their increased risk pales in comparison with the risk of adverse events of unplanned pregnancies in the United States, including a thromboembolism rate of at least 6 events per 10,000 pregnancies1 and a maternal mortality rate of 75 deaths per million live births.2
What is the best test to diagnose urinary tract stones?
Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test. (Grade of recommendation: A, based on independent blind comparison of an appropriate spectrum of patients.)
Evidence summary
Several studies demonstrating the accuracy of helical CT have been published recently.1-3 The most convincing are 2 prospective studies done in emergency departments in Belgium and Australia.1,2 Both compared helical CT with intravenous pyelography (IVP) and used the gold standard of recovery and direct visualization of a stone. The Australian study enrolled 40 consecutive patients; the Belgian study enrolled 53 of 70 consecutive patients. In these 2 studies, helical CT correctly identified every instance of urinary tract stones. In contrast, IVP failed to detect stones in a third of the patients with stones, and 44% of the negative readings were false-negatives. Both tests did well in reporting negative results for those patients without stones (specificity = 97% for both tests). In terms of likelihood ratios, helical CT and IVP had positive likelihood ratios of 29 and 19, respectively, and negative likelihood ratios of 0 and 0.36 (a lower negative likelihood ratio is better). In other words, helical CT appears to be far superior to IVP in ruling out the presence of urinary tract stones. As an additional comparison, another study found that urine dipstick testing for hematuria yielded positive likelihood ratios of 1.25 and a negative likelihood ratio of 0.55.4 The accuracy of ultrasonography appears to fall somewhere in between hematuria testing and IVP.5 The Table shows an overall comparison of these diagnostic tests.
In addition to its better accuracy, several studies discuss the better safety profile and decreased diagnostic time of helical CT than IVP.6-8 The risk of contrast reaction during IVP is between 5% and 10%, with a mortality of approximately 1 in 40,000. Helical CT (when evaluating for stones) does not use contrast, although the radiation exposure is approximately twice that of IVP.6 The costs of helical CT and IVP are comparable, and helical CT becomes more cost effective when the shorter time to discharge with a definitive diagnosis is considered.7,8 Several authors also cite instances when helical CT uncovered a nonurinary cause for patients’ symptoms that IVP would have missed.8,9
Access to helical CT is improving throughout the United States, and individual radiologists can become quickly skilled at helical CT interpretation.10 Physicians should confirm that their local radiologists are comfortable with helical CT readings before incorporating this into their diagnostic routines.
Recommendations from others
Several urology and radiology departments have published reviews lately supporting the use of helical CT over other diagnostic testing for urinary tract stones.9,11 No official recommendations from professional organizations were found.
Sang-Ick Chang, MD
University of California, San Francisco
From a practical point of view, spiral CT has been a far superior modality for diagnosis of urinary tract stones. It is much faster, avoids contrast, renal function is not an issue, and previous bowel preparation is not needed. Given the relatively poor performance of the IVP compared with spiral CT, there is no situation I can think of where IVP would be preferred over the spiral CT. The only caveat is that spiral CT is not practical in all practice settings. Still, the 56% negative predictive value for IVP is much lower than we commonly assume and renders the IVP useful mostly for information it can tell us about the size and location of any stone it finds and relatively useless for ruling out stones.
1. Niall O, Russell J, MacGregor R, Duncan H, Mullins J. A comparison of noncontrast computerized tomography with excretory urography in the assessment of acute flank pain. J Urol 1999;161:534-37.
2. Sourtzis S, Thibaeau J, Damry N, Raslan A, Vandendris M, Bellemans M. Radiologic investigation of renal colic: unenhanced CT compared with excretory urography. Am J Roentgenol 1999;172:1491-94.
3. See the JFP Web site, www.jfponline.com, for of other comparison studies.
4. Bove P, Kaplan D, DalrympleN, et al. Reexamining the value of hematuria testing in patients with acute flank pain. J Urol 1999;162:685-87.
5. Sheafor D, Hertzberg B, Freed K, et al. Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison. Radiology 2000;217:792-97.
6. Liu W, Esler S, Kenny B, Goh R, Rainbow A, Stevenson G. Low-dose nonenhanced helical CT of renal colic: assessment of ureteric stone detection and measurement of effective dose equivalent. Radiology 2000;215:51-54.
7. Patel M, Han S, Vaux K, Saalfeld J, Alexander J. A protocol of early spiral computed tomography for the detection of stones in patients with renal colic has reduced the time to diagnosis and overall management costs. Aus N Z J Surg 2000;70:39-42.
8. Chen M, Zagoria R. Can noncontrast helical computed tomography replace intravenous urography for evaluation of patients with acute urinary tract colic? J Emerg Med 1999;17:299-303.
9. Miller O, Kane C. Unenhanced helical computed tomography in the evaluation of acute flank pain. Curr Op Urol 2000;10:123-29.
10. Rosser C, Zagoria R, Dixon R, et al. Is there a learning curve in diagnosing urolithiasis with noncontrast helical computed tomography? Can Assoc Radiol J 2000;51:177-81.
11. See the JFP Web site, www.jfponline.com, for of several review articles.
Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test. (Grade of recommendation: A, based on independent blind comparison of an appropriate spectrum of patients.)
Evidence summary
Several studies demonstrating the accuracy of helical CT have been published recently.1-3 The most convincing are 2 prospective studies done in emergency departments in Belgium and Australia.1,2 Both compared helical CT with intravenous pyelography (IVP) and used the gold standard of recovery and direct visualization of a stone. The Australian study enrolled 40 consecutive patients; the Belgian study enrolled 53 of 70 consecutive patients. In these 2 studies, helical CT correctly identified every instance of urinary tract stones. In contrast, IVP failed to detect stones in a third of the patients with stones, and 44% of the negative readings were false-negatives. Both tests did well in reporting negative results for those patients without stones (specificity = 97% for both tests). In terms of likelihood ratios, helical CT and IVP had positive likelihood ratios of 29 and 19, respectively, and negative likelihood ratios of 0 and 0.36 (a lower negative likelihood ratio is better). In other words, helical CT appears to be far superior to IVP in ruling out the presence of urinary tract stones. As an additional comparison, another study found that urine dipstick testing for hematuria yielded positive likelihood ratios of 1.25 and a negative likelihood ratio of 0.55.4 The accuracy of ultrasonography appears to fall somewhere in between hematuria testing and IVP.5 The Table shows an overall comparison of these diagnostic tests.
In addition to its better accuracy, several studies discuss the better safety profile and decreased diagnostic time of helical CT than IVP.6-8 The risk of contrast reaction during IVP is between 5% and 10%, with a mortality of approximately 1 in 40,000. Helical CT (when evaluating for stones) does not use contrast, although the radiation exposure is approximately twice that of IVP.6 The costs of helical CT and IVP are comparable, and helical CT becomes more cost effective when the shorter time to discharge with a definitive diagnosis is considered.7,8 Several authors also cite instances when helical CT uncovered a nonurinary cause for patients’ symptoms that IVP would have missed.8,9
Access to helical CT is improving throughout the United States, and individual radiologists can become quickly skilled at helical CT interpretation.10 Physicians should confirm that their local radiologists are comfortable with helical CT readings before incorporating this into their diagnostic routines.
Recommendations from others
Several urology and radiology departments have published reviews lately supporting the use of helical CT over other diagnostic testing for urinary tract stones.9,11 No official recommendations from professional organizations were found.
Sang-Ick Chang, MD
University of California, San Francisco
From a practical point of view, spiral CT has been a far superior modality for diagnosis of urinary tract stones. It is much faster, avoids contrast, renal function is not an issue, and previous bowel preparation is not needed. Given the relatively poor performance of the IVP compared with spiral CT, there is no situation I can think of where IVP would be preferred over the spiral CT. The only caveat is that spiral CT is not practical in all practice settings. Still, the 56% negative predictive value for IVP is much lower than we commonly assume and renders the IVP useful mostly for information it can tell us about the size and location of any stone it finds and relatively useless for ruling out stones.
Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test. (Grade of recommendation: A, based on independent blind comparison of an appropriate spectrum of patients.)
Evidence summary
Several studies demonstrating the accuracy of helical CT have been published recently.1-3 The most convincing are 2 prospective studies done in emergency departments in Belgium and Australia.1,2 Both compared helical CT with intravenous pyelography (IVP) and used the gold standard of recovery and direct visualization of a stone. The Australian study enrolled 40 consecutive patients; the Belgian study enrolled 53 of 70 consecutive patients. In these 2 studies, helical CT correctly identified every instance of urinary tract stones. In contrast, IVP failed to detect stones in a third of the patients with stones, and 44% of the negative readings were false-negatives. Both tests did well in reporting negative results for those patients without stones (specificity = 97% for both tests). In terms of likelihood ratios, helical CT and IVP had positive likelihood ratios of 29 and 19, respectively, and negative likelihood ratios of 0 and 0.36 (a lower negative likelihood ratio is better). In other words, helical CT appears to be far superior to IVP in ruling out the presence of urinary tract stones. As an additional comparison, another study found that urine dipstick testing for hematuria yielded positive likelihood ratios of 1.25 and a negative likelihood ratio of 0.55.4 The accuracy of ultrasonography appears to fall somewhere in between hematuria testing and IVP.5 The Table shows an overall comparison of these diagnostic tests.
In addition to its better accuracy, several studies discuss the better safety profile and decreased diagnostic time of helical CT than IVP.6-8 The risk of contrast reaction during IVP is between 5% and 10%, with a mortality of approximately 1 in 40,000. Helical CT (when evaluating for stones) does not use contrast, although the radiation exposure is approximately twice that of IVP.6 The costs of helical CT and IVP are comparable, and helical CT becomes more cost effective when the shorter time to discharge with a definitive diagnosis is considered.7,8 Several authors also cite instances when helical CT uncovered a nonurinary cause for patients’ symptoms that IVP would have missed.8,9
Access to helical CT is improving throughout the United States, and individual radiologists can become quickly skilled at helical CT interpretation.10 Physicians should confirm that their local radiologists are comfortable with helical CT readings before incorporating this into their diagnostic routines.
Recommendations from others
Several urology and radiology departments have published reviews lately supporting the use of helical CT over other diagnostic testing for urinary tract stones.9,11 No official recommendations from professional organizations were found.
Sang-Ick Chang, MD
University of California, San Francisco
From a practical point of view, spiral CT has been a far superior modality for diagnosis of urinary tract stones. It is much faster, avoids contrast, renal function is not an issue, and previous bowel preparation is not needed. Given the relatively poor performance of the IVP compared with spiral CT, there is no situation I can think of where IVP would be preferred over the spiral CT. The only caveat is that spiral CT is not practical in all practice settings. Still, the 56% negative predictive value for IVP is much lower than we commonly assume and renders the IVP useful mostly for information it can tell us about the size and location of any stone it finds and relatively useless for ruling out stones.
1. Niall O, Russell J, MacGregor R, Duncan H, Mullins J. A comparison of noncontrast computerized tomography with excretory urography in the assessment of acute flank pain. J Urol 1999;161:534-37.
2. Sourtzis S, Thibaeau J, Damry N, Raslan A, Vandendris M, Bellemans M. Radiologic investigation of renal colic: unenhanced CT compared with excretory urography. Am J Roentgenol 1999;172:1491-94.
3. See the JFP Web site, www.jfponline.com, for of other comparison studies.
4. Bove P, Kaplan D, DalrympleN, et al. Reexamining the value of hematuria testing in patients with acute flank pain. J Urol 1999;162:685-87.
5. Sheafor D, Hertzberg B, Freed K, et al. Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison. Radiology 2000;217:792-97.
6. Liu W, Esler S, Kenny B, Goh R, Rainbow A, Stevenson G. Low-dose nonenhanced helical CT of renal colic: assessment of ureteric stone detection and measurement of effective dose equivalent. Radiology 2000;215:51-54.
7. Patel M, Han S, Vaux K, Saalfeld J, Alexander J. A protocol of early spiral computed tomography for the detection of stones in patients with renal colic has reduced the time to diagnosis and overall management costs. Aus N Z J Surg 2000;70:39-42.
8. Chen M, Zagoria R. Can noncontrast helical computed tomography replace intravenous urography for evaluation of patients with acute urinary tract colic? J Emerg Med 1999;17:299-303.
9. Miller O, Kane C. Unenhanced helical computed tomography in the evaluation of acute flank pain. Curr Op Urol 2000;10:123-29.
10. Rosser C, Zagoria R, Dixon R, et al. Is there a learning curve in diagnosing urolithiasis with noncontrast helical computed tomography? Can Assoc Radiol J 2000;51:177-81.
11. See the JFP Web site, www.jfponline.com, for of several review articles.
1. Niall O, Russell J, MacGregor R, Duncan H, Mullins J. A comparison of noncontrast computerized tomography with excretory urography in the assessment of acute flank pain. J Urol 1999;161:534-37.
2. Sourtzis S, Thibaeau J, Damry N, Raslan A, Vandendris M, Bellemans M. Radiologic investigation of renal colic: unenhanced CT compared with excretory urography. Am J Roentgenol 1999;172:1491-94.
3. See the JFP Web site, www.jfponline.com, for of other comparison studies.
4. Bove P, Kaplan D, DalrympleN, et al. Reexamining the value of hematuria testing in patients with acute flank pain. J Urol 1999;162:685-87.
5. Sheafor D, Hertzberg B, Freed K, et al. Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison. Radiology 2000;217:792-97.
6. Liu W, Esler S, Kenny B, Goh R, Rainbow A, Stevenson G. Low-dose nonenhanced helical CT of renal colic: assessment of ureteric stone detection and measurement of effective dose equivalent. Radiology 2000;215:51-54.
7. Patel M, Han S, Vaux K, Saalfeld J, Alexander J. A protocol of early spiral computed tomography for the detection of stones in patients with renal colic has reduced the time to diagnosis and overall management costs. Aus N Z J Surg 2000;70:39-42.
8. Chen M, Zagoria R. Can noncontrast helical computed tomography replace intravenous urography for evaluation of patients with acute urinary tract colic? J Emerg Med 1999;17:299-303.
9. Miller O, Kane C. Unenhanced helical computed tomography in the evaluation of acute flank pain. Curr Op Urol 2000;10:123-29.
10. Rosser C, Zagoria R, Dixon R, et al. Is there a learning curve in diagnosing urolithiasis with noncontrast helical computed tomography? Can Assoc Radiol J 2000;51:177-81.
11. See the JFP Web site, www.jfponline.com, for of several review articles.
Evidence-based answers from the Family Physicians Inquiries Network