Neil Korsen, MD

Evidence summary

Two randomized controlledtrials and 1 cohort study demonstrated a decrease in all-cause mortality in individuals aged 65 and older with known CHD by treating elevated cholesterol levels with either pravastatin or simvastatin.^1-3 The overall decrease in absolute risk of death was similar (range, 4.1%–6.2%; numbers needed to treat [NNT] = 17–25). The LIPID trial demonstrated a reduction in CHD-related death (relative risk [RR] = 0.76; 95% CI, 0.62–0.93; NNT = 37) and myocardial infarctions (RR = 0.74; 95% CI, 0.60–0.91; NNT = 36) in elderly patients taking pravastatin 40 mg once daily for 6 years compared with placebo.³

Unfortunately, no comparable evidence is available to guide practitioners in their care of older patients without known CHD. A 1993 report on results of the Framingham study showed the association between all-cause mortality and cholesterol level only in individuals younger than 50 years.⁴ Two other cohort studies showed an association between elevated cholesterol levels and increased CHD mortality.^5,6 It is unclear whether all-cause or CHD mortality is the better outcome to measure.

The best available evidence addressing the benefit of lowering lipid levels in persons with elevated cholesterol but without CHD is from the West of Scotland Coronary Prevention study, which included patients aged 45 to 64 years.⁷ This study showed a 0.5% reduction in CHD mortality (NNT = 200) and a 0.9% reduction in all-cause mortality (NNT = 111). Neither reduction reached statistical significance.

Several reports have demonstrated that statins safely and effectively lower cholesterol levels in patients aged 65 and older.^1-3,8,9 Moreover, statins do not decrease health-related quality of life.¹⁰ Approximately 1% to 4% of those who take statins experience side effects, including abnormal liver function, arthralgias, myalgias, rash, sinusitis, and diarrhea.

Recommendations from others

The National Cholesterol Education Program published its updated guidelines in 2001, lending support for statin treatment of elevated low-density lipoprotein cholesterol levels in selected men aged 65 or older and women aged 75 or older without CHD.¹¹ The target low-density lipoprotein level varied from 100 to 160 mg/dL depending on presence of other cardiac risk factors. The recommendation emphasized lifestyle changes, noninvasive testing for subclinical atherosclerosis, and consideration of treatment for individuals with extensive subclinical disease or multiple risk factors, rather than focusing merely on chronological age.

Clinical Commentary by Nicholas Solomos, MD, at http://www.fpin.org.

Evidence summary

Two randomized controlledtrials and 1 cohort study demonstrated a decrease in all-cause mortality in individuals aged 65 and older with known CHD by treating elevated cholesterol levels with either pravastatin or simvastatin.^1-3 The overall decrease in absolute risk of death was similar (range, 4.1%–6.2%; numbers needed to treat [NNT] = 17–25). The LIPID trial demonstrated a reduction in CHD-related death (relative risk [RR] = 0.76; 95% CI, 0.62–0.93; NNT = 37) and myocardial infarctions (RR = 0.74; 95% CI, 0.60–0.91; NNT = 36) in elderly patients taking pravastatin 40 mg once daily for 6 years compared with placebo.³

Unfortunately, no comparable evidence is available to guide practitioners in their care of older patients without known CHD. A 1993 report on results of the Framingham study showed the association between all-cause mortality and cholesterol level only in individuals younger than 50 years.⁴ Two other cohort studies showed an association between elevated cholesterol levels and increased CHD mortality.^5,6 It is unclear whether all-cause or CHD mortality is the better outcome to measure.

The best available evidence addressing the benefit of lowering lipid levels in persons with elevated cholesterol but without CHD is from the West of Scotland Coronary Prevention study, which included patients aged 45 to 64 years.⁷ This study showed a 0.5% reduction in CHD mortality (NNT = 200) and a 0.9% reduction in all-cause mortality (NNT = 111). Neither reduction reached statistical significance.

Several reports have demonstrated that statins safely and effectively lower cholesterol levels in patients aged 65 and older.^1-3,8,9 Moreover, statins do not decrease health-related quality of life.¹⁰ Approximately 1% to 4% of those who take statins experience side effects, including abnormal liver function, arthralgias, myalgias, rash, sinusitis, and diarrhea.

Recommendations from others

The National Cholesterol Education Program published its updated guidelines in 2001, lending support for statin treatment of elevated low-density lipoprotein cholesterol levels in selected men aged 65 or older and women aged 75 or older without CHD.¹¹ The target low-density lipoprotein level varied from 100 to 160 mg/dL depending on presence of other cardiac risk factors. The recommendation emphasized lifestyle changes, noninvasive testing for subclinical atherosclerosis, and consideration of treatment for individuals with extensive subclinical disease or multiple risk factors, rather than focusing merely on chronological age.

Clinical Commentary by Nicholas Solomos, MD, at http://www.fpin.org.

Evidence summary

Two randomized controlledtrials and 1 cohort study demonstrated a decrease in all-cause mortality in individuals aged 65 and older with known CHD by treating elevated cholesterol levels with either pravastatin or simvastatin.^1-3 The overall decrease in absolute risk of death was similar (range, 4.1%–6.2%; numbers needed to treat [NNT] = 17–25). The LIPID trial demonstrated a reduction in CHD-related death (relative risk [RR] = 0.76; 95% CI, 0.62–0.93; NNT = 37) and myocardial infarctions (RR = 0.74; 95% CI, 0.60–0.91; NNT = 36) in elderly patients taking pravastatin 40 mg once daily for 6 years compared with placebo.³

Unfortunately, no comparable evidence is available to guide practitioners in their care of older patients without known CHD. A 1993 report on results of the Framingham study showed the association between all-cause mortality and cholesterol level only in individuals younger than 50 years.⁴ Two other cohort studies showed an association between elevated cholesterol levels and increased CHD mortality.^5,6 It is unclear whether all-cause or CHD mortality is the better outcome to measure.

The best available evidence addressing the benefit of lowering lipid levels in persons with elevated cholesterol but without CHD is from the West of Scotland Coronary Prevention study, which included patients aged 45 to 64 years.⁷ This study showed a 0.5% reduction in CHD mortality (NNT = 200) and a 0.9% reduction in all-cause mortality (NNT = 111). Neither reduction reached statistical significance.

Several reports have demonstrated that statins safely and effectively lower cholesterol levels in patients aged 65 and older.^1-3,8,9 Moreover, statins do not decrease health-related quality of life.¹⁰ Approximately 1% to 4% of those who take statins experience side effects, including abnormal liver function, arthralgias, myalgias, rash, sinusitis, and diarrhea.

Recommendations from others

The National Cholesterol Education Program published its updated guidelines in 2001, lending support for statin treatment of elevated low-density lipoprotein cholesterol levels in selected men aged 65 or older and women aged 75 or older without CHD.¹¹ The target low-density lipoprotein level varied from 100 to 160 mg/dL depending on presence of other cardiac risk factors. The recommendation emphasized lifestyle changes, noninvasive testing for subclinical atherosclerosis, and consideration of treatment for individuals with extensive subclinical disease or multiple risk factors, rather than focusing merely on chronological age.

Clinical Commentary by Nicholas Solomos, MD, at http://www.fpin.org.

BACKGROUND: More than 260,000 cases of pulmonary embolism (PE) are diagnosed each year in the United States. However, the prevalence of PE is estimated to be only 25% to 35% of suspected cases. Commonly used noninvasive diagnostic tools (D-dimer levels, ventilation/perfusion scan, doppler ultrasonography) are inconclusive in a significant number of cases, leading to invasive testing with angiography. Helical computerized tomography (CT) scanning has been suggested by some as a useful test in the diagnosis of PE. This article attempts to address the role of this test in the diagnostic evaluation of those with suspected PE.

POPULATION STUDIED: We studied all adult patients (older than 6 years) presenting to the emergency department of a community teaching hospital in Geneva, Switzerland, over a 25-month period with suspected pulmonary embolism and elevated plasma D-dimer level greater than 500 μg/L. Of the initial 1108 patients enrolled in the study, 35% were excluded on the basis of a normal D-dimer level. Another 38% were excluded on the basis of reasonable criteria (ie, contraindication to CT, declining to participate, taking oral anticoagulants, CT results unavailable or unblinded). There was no clinically significant difference in age, sex, risk factors, clinical presentation, and clinical probability of PE between those included and those excluded.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which 229 patients were evaluated and treated according to the hospital’s current practices. In addition to the usual studies, CT scans were performed on all patients, with results withheld from the treating physician so as to not influence diagnosis and treatment. CT interpretation was performed more than 3 months after acquisition of the films by 3 radiologists who were blinded to all other clinical data and test results. PE was diagnosed if the patient had a positive angiogram, a high-probability lung scan, or DVT and a clinical suspicion of PE. PE was ruled out if the patient had a normal angiogram, a normal or near-normal lung scan, or low clinical suspicion with a nondiagnostic lung scan and no evidence of DVT. Results from the CT were compared with these gold standards. In addition, patients were followed for 3 months for evidence of DVT or PE. It is important to note that the results of the study can only be applied to patients initially presenting as outpatients who were found to have elevated D-dimer levels. The study is well done. The gold standards chosen are reasonable, and the patient population is appropriate; these are the patients for whom the question of whether to proceed to angiography is important.

OUTCOMES MEASURED: Sensitivity and specificity of helical CT in diagnosing PE with and without other diagnostic modalities.

RESULTS: Approximately 40% of the 299 patients with positive D-dimer levels were eventually found to have PE (prevalence = 40%). Of these, the helical CT scan correctly identified 70% (confidence interval [CI], 62%-78%) of patients with embolism and correctly identified as negative 91% (CI, 86%-95%) of patients without embolism (positive likelihood ratio=8.0; negative likelihood ratio=0.3). These results were unchanged by the application of more stringent diagnostic criteria (high-probability scan, low-probability scan, or angiography). The false-negative rate of 30% decreased to 21% in patients who had a positive D-dimer level but negative ultrasound before CT. When used as a fourth-line diagnostic test, after a positive D-dimer, normal ultrasound, and inconclusive pulmonary scan, the false-negative rate decreased to 5% and the false-positive rate decreased to 7%.

BACKGROUND: More than 260,000 cases of pulmonary embolism (PE) are diagnosed each year in the United States. However, the prevalence of PE is estimated to be only 25% to 35% of suspected cases. Commonly used noninvasive diagnostic tools (D-dimer levels, ventilation/perfusion scan, doppler ultrasonography) are inconclusive in a significant number of cases, leading to invasive testing with angiography. Helical computerized tomography (CT) scanning has been suggested by some as a useful test in the diagnosis of PE. This article attempts to address the role of this test in the diagnostic evaluation of those with suspected PE.

POPULATION STUDIED: We studied all adult patients (older than 6 years) presenting to the emergency department of a community teaching hospital in Geneva, Switzerland, over a 25-month period with suspected pulmonary embolism and elevated plasma D-dimer level greater than 500 μg/L. Of the initial 1108 patients enrolled in the study, 35% were excluded on the basis of a normal D-dimer level. Another 38% were excluded on the basis of reasonable criteria (ie, contraindication to CT, declining to participate, taking oral anticoagulants, CT results unavailable or unblinded). There was no clinically significant difference in age, sex, risk factors, clinical presentation, and clinical probability of PE between those included and those excluded.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which 229 patients were evaluated and treated according to the hospital’s current practices. In addition to the usual studies, CT scans were performed on all patients, with results withheld from the treating physician so as to not influence diagnosis and treatment. CT interpretation was performed more than 3 months after acquisition of the films by 3 radiologists who were blinded to all other clinical data and test results. PE was diagnosed if the patient had a positive angiogram, a high-probability lung scan, or DVT and a clinical suspicion of PE. PE was ruled out if the patient had a normal angiogram, a normal or near-normal lung scan, or low clinical suspicion with a nondiagnostic lung scan and no evidence of DVT. Results from the CT were compared with these gold standards. In addition, patients were followed for 3 months for evidence of DVT or PE. It is important to note that the results of the study can only be applied to patients initially presenting as outpatients who were found to have elevated D-dimer levels. The study is well done. The gold standards chosen are reasonable, and the patient population is appropriate; these are the patients for whom the question of whether to proceed to angiography is important.

OUTCOMES MEASURED: Sensitivity and specificity of helical CT in diagnosing PE with and without other diagnostic modalities.

RESULTS: Approximately 40% of the 299 patients with positive D-dimer levels were eventually found to have PE (prevalence = 40%). Of these, the helical CT scan correctly identified 70% (confidence interval [CI], 62%-78%) of patients with embolism and correctly identified as negative 91% (CI, 86%-95%) of patients without embolism (positive likelihood ratio=8.0; negative likelihood ratio=0.3). These results were unchanged by the application of more stringent diagnostic criteria (high-probability scan, low-probability scan, or angiography). The false-negative rate of 30% decreased to 21% in patients who had a positive D-dimer level but negative ultrasound before CT. When used as a fourth-line diagnostic test, after a positive D-dimer, normal ultrasound, and inconclusive pulmonary scan, the false-negative rate decreased to 5% and the false-positive rate decreased to 7%.

BACKGROUND: More than 260,000 cases of pulmonary embolism (PE) are diagnosed each year in the United States. However, the prevalence of PE is estimated to be only 25% to 35% of suspected cases. Commonly used noninvasive diagnostic tools (D-dimer levels, ventilation/perfusion scan, doppler ultrasonography) are inconclusive in a significant number of cases, leading to invasive testing with angiography. Helical computerized tomography (CT) scanning has been suggested by some as a useful test in the diagnosis of PE. This article attempts to address the role of this test in the diagnostic evaluation of those with suspected PE.

POPULATION STUDIED: We studied all adult patients (older than 6 years) presenting to the emergency department of a community teaching hospital in Geneva, Switzerland, over a 25-month period with suspected pulmonary embolism and elevated plasma D-dimer level greater than 500 μg/L. Of the initial 1108 patients enrolled in the study, 35% were excluded on the basis of a normal D-dimer level. Another 38% were excluded on the basis of reasonable criteria (ie, contraindication to CT, declining to participate, taking oral anticoagulants, CT results unavailable or unblinded). There was no clinically significant difference in age, sex, risk factors, clinical presentation, and clinical probability of PE between those included and those excluded.

STUDY DESIGN AND VALIDITY: This was a prospective cohort study in which 229 patients were evaluated and treated according to the hospital’s current practices. In addition to the usual studies, CT scans were performed on all patients, with results withheld from the treating physician so as to not influence diagnosis and treatment. CT interpretation was performed more than 3 months after acquisition of the films by 3 radiologists who were blinded to all other clinical data and test results. PE was diagnosed if the patient had a positive angiogram, a high-probability lung scan, or DVT and a clinical suspicion of PE. PE was ruled out if the patient had a normal angiogram, a normal or near-normal lung scan, or low clinical suspicion with a nondiagnostic lung scan and no evidence of DVT. Results from the CT were compared with these gold standards. In addition, patients were followed for 3 months for evidence of DVT or PE. It is important to note that the results of the study can only be applied to patients initially presenting as outpatients who were found to have elevated D-dimer levels. The study is well done. The gold standards chosen are reasonable, and the patient population is appropriate; these are the patients for whom the question of whether to proceed to angiography is important.

OUTCOMES MEASURED: Sensitivity and specificity of helical CT in diagnosing PE with and without other diagnostic modalities.

RESULTS: Approximately 40% of the 299 patients with positive D-dimer levels were eventually found to have PE (prevalence = 40%). Of these, the helical CT scan correctly identified 70% (confidence interval [CI], 62%-78%) of patients with embolism and correctly identified as negative 91% (CI, 86%-95%) of patients without embolism (positive likelihood ratio=8.0; negative likelihood ratio=0.3). These results were unchanged by the application of more stringent diagnostic criteria (high-probability scan, low-probability scan, or angiography). The false-negative rate of 30% decreased to 21% in patients who had a positive D-dimer level but negative ultrasound before CT. When used as a fourth-line diagnostic test, after a positive D-dimer, normal ultrasound, and inconclusive pulmonary scan, the false-negative rate decreased to 5% and the false-positive rate decreased to 7%.

BACKGROUND: Though cholesterol-lowering therapy can reduce cardiovascular morbidity and mortality, earlier studies raised concerns that reducing cholesterol concentrations might increase the risk of cancer and deaths from suicides, accidents, and violence (ie, nonillness mortality).

POPULATION STUDIED: This meta-analysis included clinical trials of cholesterol-lowering treatments in which participants were randomly assigned to a cholesterol-lowering intervention group or a control group. The investigators only included trials designed to measure effects of treatment on clinical events and mortality. Most participants were men aged between 40 and 70 years.

STUDY DESIGN AND VALIDITY: The studies were identified using an ancestry approach (locating previous studies cited in reference lists of already identified studies cited in reference articles) and a MEDLINE computer literature search from 1966 to March 2000. A total of 21 trials met inclusion criteria, though only 15 contained data on nonillness mortality. Some investigators provided previously unpublished data for 4 trials, yielding data from 19 of the 21 trials. The included studies investigated cholesterol-lowering either by drug therapy, diet modification, or both. The most common reasons for exclusion were the use of multifactorial risk interventions and studies not designed to monitor clinical events and cause-specific mortality.

OUTCOMES MEASURED: The outcomes were nonillness mortality, including suicides, accidents, and violence.

RESULTS: The studies that met inclusion criteria generated approximately 338,000 patient-years of randomized clinical trial data. Overall, treatments with the goal of lower total cholesterol did not affect the rate of nonillness mortality (odd ratio [OR]=1.18; 95% confidence interval [CI], 0.91-1.52). There was no effect in studies of primary prevention, secondary prevention, or studies of the “statin” drugs. Trials of diet and non-statin drugs (13 trials including 39,260 patients) also did not show a difference, although there was a trend toward increased nonillness mortality (OR=1.32; 95% CI, 0.98-1.77; P=.06). The absolute risk increase in these trials was 4.7 per 1000, which translates to a number needed to harm of 213.The rate of nonillness mortality was not related to the degree of cholesterol reduction.

BACKGROUND: Though cholesterol-lowering therapy can reduce cardiovascular morbidity and mortality, earlier studies raised concerns that reducing cholesterol concentrations might increase the risk of cancer and deaths from suicides, accidents, and violence (ie, nonillness mortality).

POPULATION STUDIED: This meta-analysis included clinical trials of cholesterol-lowering treatments in which participants were randomly assigned to a cholesterol-lowering intervention group or a control group. The investigators only included trials designed to measure effects of treatment on clinical events and mortality. Most participants were men aged between 40 and 70 years.

STUDY DESIGN AND VALIDITY: The studies were identified using an ancestry approach (locating previous studies cited in reference lists of already identified studies cited in reference articles) and a MEDLINE computer literature search from 1966 to March 2000. A total of 21 trials met inclusion criteria, though only 15 contained data on nonillness mortality. Some investigators provided previously unpublished data for 4 trials, yielding data from 19 of the 21 trials. The included studies investigated cholesterol-lowering either by drug therapy, diet modification, or both. The most common reasons for exclusion were the use of multifactorial risk interventions and studies not designed to monitor clinical events and cause-specific mortality.

OUTCOMES MEASURED: The outcomes were nonillness mortality, including suicides, accidents, and violence.

RESULTS: The studies that met inclusion criteria generated approximately 338,000 patient-years of randomized clinical trial data. Overall, treatments with the goal of lower total cholesterol did not affect the rate of nonillness mortality (odd ratio [OR]=1.18; 95% confidence interval [CI], 0.91-1.52). There was no effect in studies of primary prevention, secondary prevention, or studies of the “statin” drugs. Trials of diet and non-statin drugs (13 trials including 39,260 patients) also did not show a difference, although there was a trend toward increased nonillness mortality (OR=1.32; 95% CI, 0.98-1.77; P=.06). The absolute risk increase in these trials was 4.7 per 1000, which translates to a number needed to harm of 213.The rate of nonillness mortality was not related to the degree of cholesterol reduction.

BACKGROUND: Though cholesterol-lowering therapy can reduce cardiovascular morbidity and mortality, earlier studies raised concerns that reducing cholesterol concentrations might increase the risk of cancer and deaths from suicides, accidents, and violence (ie, nonillness mortality).

POPULATION STUDIED: This meta-analysis included clinical trials of cholesterol-lowering treatments in which participants were randomly assigned to a cholesterol-lowering intervention group or a control group. The investigators only included trials designed to measure effects of treatment on clinical events and mortality. Most participants were men aged between 40 and 70 years.

STUDY DESIGN AND VALIDITY: The studies were identified using an ancestry approach (locating previous studies cited in reference lists of already identified studies cited in reference articles) and a MEDLINE computer literature search from 1966 to March 2000. A total of 21 trials met inclusion criteria, though only 15 contained data on nonillness mortality. Some investigators provided previously unpublished data for 4 trials, yielding data from 19 of the 21 trials. The included studies investigated cholesterol-lowering either by drug therapy, diet modification, or both. The most common reasons for exclusion were the use of multifactorial risk interventions and studies not designed to monitor clinical events and cause-specific mortality.

OUTCOMES MEASURED: The outcomes were nonillness mortality, including suicides, accidents, and violence.

RESULTS: The studies that met inclusion criteria generated approximately 338,000 patient-years of randomized clinical trial data. Overall, treatments with the goal of lower total cholesterol did not affect the rate of nonillness mortality (odd ratio [OR]=1.18; 95% confidence interval [CI], 0.91-1.52). There was no effect in studies of primary prevention, secondary prevention, or studies of the “statin” drugs. Trials of diet and non-statin drugs (13 trials including 39,260 patients) also did not show a difference, although there was a trend toward increased nonillness mortality (OR=1.32; 95% CI, 0.98-1.77; P=.06). The absolute risk increase in these trials was 4.7 per 1000, which translates to a number needed to harm of 213.The rate of nonillness mortality was not related to the degree of cholesterol reduction.