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How accurate is stress radionuclide imaging for diagnosis of CAD?
Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals.
Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women (strength of recommendation [SOR]: A, based on multiple meta-analyses). Abnormal stress radionuclide screening in vascular surgical candidates also predicts an increased rate of perioperative cardiac events (SOR: A, based on meta-analysis).
Evidence summary
Stress radionuclide imaging—specifically its diagnostic accuracy—has been the subject of numerous studies. Detrano et al1 reported the first pooled data (56 studies); they concluded that estimates of sensitivity (85%) and specificity (85%) are biased by studies that were not blinded, included subjects with prior myocardial infarction (MI), or had a work-up (verification) bias (ie, use of the gold standard test is affected by the result on the test under question).
Another systematic review reported estimates of sensitivity ranging from 68% to 96% and specificity from 65% to 100%.2 The review was accompanied by a position paper from the American College of Physicians stating that the test may be appropriate for a patient with intermediate risk of coronary artery disease.3
Four meta-analyses report diagnostic accuracy of radionuclide cardiac imaging (Table). Kwok et al6 analyzed data on women only and found decreased diagnostic accuracy in this population. Kim et al7 analyzed pharmacologic stressors used with SPECT and confirmed that accuracy is near that of exercise SPECT. Patient-centered outcomes were reported in a meta-analysis of dipyridamole-thallium imaging in the preoperative evaluation of vascular surgery patients. The summary odds ratio for any perioperative cardiac event (in patients with abnormal tests) was 3.5 (95% confidence interval [CI], 2.5–4.8); the odds ratio for MI or cardiac death was 3.9 (95% CI, 2.5–5.6), leading the authors to conclude that there is sound evidence to use radionuclide testing in intermedi.ate-risk patients during preoperative screening.8
TABLE
Diagnostic accuracy reported in meta-analyses of cardiac radionuclide SPECT imaging
| Authors, year | Studies | Sn % (95% CI) | Sp % (95% CI) | LR+ | LR– |
|---|---|---|---|---|---|
| Garber and Solomon 19944 | 8 | 88 (73–98) | 77 (53–96) | 3.8 | 0.16 |
| Fleischmann et al, et al 19985 | 27 | 87 (86–88) | 64 (60–68) | 2.4 | 0.20 |
| Kwok et al, 19966 | 3 | 78 (69–87) | 58 (51–66) | 1.9 | 0.38 |
| Kim et al, 20017 | 44 | 90 (89–92)* | 75 (70–79)* | 3.6 | 0.13 |
| 89 (84–93)† | 65 (54–74)† | 2.5 | 0.17 | ||
| 82(77–87)‡ | 73 (70–79)‡ | 3.0 | 0.25 | ||
| *Adenosine SPECT | |||||
| †Dipyridamole SPECT | |||||
| ‡Dobutamine SPECT | |||||
| SPECT, single-photon emission computed tomography; SN, sensitivity; Sp, specifity; LR+, positive likelihood ratio; LR–, negative likelihood ratio; Cl, confidence interval | |||||
Recommendations from others
The American Heart Association/American College Cardiology (AHA/ACC) Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures and the American Society of Nuclear Cardiology updated guidelines for cardiac radionuclide imaging in 2003. In this consensus statement (a nonsystematic review of literature and expert opinion), they reported test characteristics to detect a 50% angiographic lesion as follows—exercise SPECT: sensitivity 87%, specificity 73%; vasodilator (adenosine or dipyridamole) SPECT: sensitivity 89%, specificity 75%. They noted that quantitative analysis performs as well as qualitative analysis of radionuclide images. Gated SPECT is slightly more specific and just as sensitive as nongated SPECT.
The Taskforce recommended that radionuclide perfusion scans be performed in patients with baseline electrocardiogram (ECG) abnormalities (such as left bundle branch block, hypertrophy, digitalis effect, etc), patients who cannot perform an exercise stress test, and to assess the functional effect of indeterminate lesions found on angiography. They also note that the repeat use of radionuclide testing 3 to 5 years after an event in asymptomatic high-risk patients and the initial use of radionuclide testing in patients at very high risk are both somewhat controversial, but the weight of limited evidence suggests some benefit to their use.9
ECG stress still the choice; image those with abnormal ECG or unable to exercise
David Kilgore, MD
Tacoma Family Medicine, Tacoma, Wash
Primary care providers frequently face the question of how best to evaluate patients with suspected CAD. Recent studies and expert opinion appear to give conflicting advice regarding the merits of plain exercise ECG vs stress imaging. Information on accuracy doesn’t always indicate which test is best for a patient.
Though quoted sensitivities and specificities for exercise ECG typically appear lower than those for stress imaging, costs for stress imaging are significantly higher, and numerous recent studies are demonstrating mortality outcome differences obtainable from physiologic information found in exercise testing (exercise capacity, blood pressure and pulse changes, time to angina).
Currently, the best choice for evaluation appears to be summarized by the 2003 AHA/ACC practice guidelines, which endorse exercise ECG for patients (women included) with intermediate pretest risk, and normal resting ECG for those who are unable to exercise. Stress imaging is cost effective for those patients with abnormal baseline ECG (left bundle branch block, ST abnormalities), or who are unable to exercise.
1. Detrano R, Janosi A, Lyons KP, Marcondes G, Abbassi N, Froelicher VF. Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram. Am J Med 1988;84:699-710.
2. Kotler TS, Diamond GA. Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. Ann Intern Med 1990;113:684-702.
3. Efficacy of exercise thallium-201 scintigraphy in diagnosis and prognosis of coronary artery disease. American College of Physicians. Ann Intern Med 1990;113:703-704.
4. Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 1999;130:719-728.
5. Fleischmann KE, Hunink MG, Kuntz KM, Douglas PS. Exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA 1998;280:913-920.
6. Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660-666.
7. Kim C, Kwok YS, Heagerty P, Redberg R. Pharmacologic stress testing for coronary artery disease diagnosis: A meta-analysis. Am Heart J 2001;142:934-944.
8. Shaw LJ, Eagle KA, Gersh BJ, Miller DD. Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985–1994) and dobutamine echocardiography (1991–1994) for risk stratification before vascular surgery. J Am Coll Cardiol 1996;27:787-798.
9. Klocke FJ, Baird MG, Bateman TM, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Radionuclide Imaging. Available at: www.acc.org/clinical/guidelines/radio/rni_fulltext.pdf. Accessed on December 14, 2003.
Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals.
Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women (strength of recommendation [SOR]: A, based on multiple meta-analyses). Abnormal stress radionuclide screening in vascular surgical candidates also predicts an increased rate of perioperative cardiac events (SOR: A, based on meta-analysis).
Evidence summary
Stress radionuclide imaging—specifically its diagnostic accuracy—has been the subject of numerous studies. Detrano et al1 reported the first pooled data (56 studies); they concluded that estimates of sensitivity (85%) and specificity (85%) are biased by studies that were not blinded, included subjects with prior myocardial infarction (MI), or had a work-up (verification) bias (ie, use of the gold standard test is affected by the result on the test under question).
Another systematic review reported estimates of sensitivity ranging from 68% to 96% and specificity from 65% to 100%.2 The review was accompanied by a position paper from the American College of Physicians stating that the test may be appropriate for a patient with intermediate risk of coronary artery disease.3
Four meta-analyses report diagnostic accuracy of radionuclide cardiac imaging (Table). Kwok et al6 analyzed data on women only and found decreased diagnostic accuracy in this population. Kim et al7 analyzed pharmacologic stressors used with SPECT and confirmed that accuracy is near that of exercise SPECT. Patient-centered outcomes were reported in a meta-analysis of dipyridamole-thallium imaging in the preoperative evaluation of vascular surgery patients. The summary odds ratio for any perioperative cardiac event (in patients with abnormal tests) was 3.5 (95% confidence interval [CI], 2.5–4.8); the odds ratio for MI or cardiac death was 3.9 (95% CI, 2.5–5.6), leading the authors to conclude that there is sound evidence to use radionuclide testing in intermedi.ate-risk patients during preoperative screening.8
TABLE
Diagnostic accuracy reported in meta-analyses of cardiac radionuclide SPECT imaging
| Authors, year | Studies | Sn % (95% CI) | Sp % (95% CI) | LR+ | LR– |
|---|---|---|---|---|---|
| Garber and Solomon 19944 | 8 | 88 (73–98) | 77 (53–96) | 3.8 | 0.16 |
| Fleischmann et al, et al 19985 | 27 | 87 (86–88) | 64 (60–68) | 2.4 | 0.20 |
| Kwok et al, 19966 | 3 | 78 (69–87) | 58 (51–66) | 1.9 | 0.38 |
| Kim et al, 20017 | 44 | 90 (89–92)* | 75 (70–79)* | 3.6 | 0.13 |
| 89 (84–93)† | 65 (54–74)† | 2.5 | 0.17 | ||
| 82(77–87)‡ | 73 (70–79)‡ | 3.0 | 0.25 | ||
| *Adenosine SPECT | |||||
| †Dipyridamole SPECT | |||||
| ‡Dobutamine SPECT | |||||
| SPECT, single-photon emission computed tomography; SN, sensitivity; Sp, specifity; LR+, positive likelihood ratio; LR–, negative likelihood ratio; Cl, confidence interval | |||||
Recommendations from others
The American Heart Association/American College Cardiology (AHA/ACC) Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures and the American Society of Nuclear Cardiology updated guidelines for cardiac radionuclide imaging in 2003. In this consensus statement (a nonsystematic review of literature and expert opinion), they reported test characteristics to detect a 50% angiographic lesion as follows—exercise SPECT: sensitivity 87%, specificity 73%; vasodilator (adenosine or dipyridamole) SPECT: sensitivity 89%, specificity 75%. They noted that quantitative analysis performs as well as qualitative analysis of radionuclide images. Gated SPECT is slightly more specific and just as sensitive as nongated SPECT.
The Taskforce recommended that radionuclide perfusion scans be performed in patients with baseline electrocardiogram (ECG) abnormalities (such as left bundle branch block, hypertrophy, digitalis effect, etc), patients who cannot perform an exercise stress test, and to assess the functional effect of indeterminate lesions found on angiography. They also note that the repeat use of radionuclide testing 3 to 5 years after an event in asymptomatic high-risk patients and the initial use of radionuclide testing in patients at very high risk are both somewhat controversial, but the weight of limited evidence suggests some benefit to their use.9
ECG stress still the choice; image those with abnormal ECG or unable to exercise
David Kilgore, MD
Tacoma Family Medicine, Tacoma, Wash
Primary care providers frequently face the question of how best to evaluate patients with suspected CAD. Recent studies and expert opinion appear to give conflicting advice regarding the merits of plain exercise ECG vs stress imaging. Information on accuracy doesn’t always indicate which test is best for a patient.
Though quoted sensitivities and specificities for exercise ECG typically appear lower than those for stress imaging, costs for stress imaging are significantly higher, and numerous recent studies are demonstrating mortality outcome differences obtainable from physiologic information found in exercise testing (exercise capacity, blood pressure and pulse changes, time to angina).
Currently, the best choice for evaluation appears to be summarized by the 2003 AHA/ACC practice guidelines, which endorse exercise ECG for patients (women included) with intermediate pretest risk, and normal resting ECG for those who are unable to exercise. Stress imaging is cost effective for those patients with abnormal baseline ECG (left bundle branch block, ST abnormalities), or who are unable to exercise.
Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals.
Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women (strength of recommendation [SOR]: A, based on multiple meta-analyses). Abnormal stress radionuclide screening in vascular surgical candidates also predicts an increased rate of perioperative cardiac events (SOR: A, based on meta-analysis).
Evidence summary
Stress radionuclide imaging—specifically its diagnostic accuracy—has been the subject of numerous studies. Detrano et al1 reported the first pooled data (56 studies); they concluded that estimates of sensitivity (85%) and specificity (85%) are biased by studies that were not blinded, included subjects with prior myocardial infarction (MI), or had a work-up (verification) bias (ie, use of the gold standard test is affected by the result on the test under question).
Another systematic review reported estimates of sensitivity ranging from 68% to 96% and specificity from 65% to 100%.2 The review was accompanied by a position paper from the American College of Physicians stating that the test may be appropriate for a patient with intermediate risk of coronary artery disease.3
Four meta-analyses report diagnostic accuracy of radionuclide cardiac imaging (Table). Kwok et al6 analyzed data on women only and found decreased diagnostic accuracy in this population. Kim et al7 analyzed pharmacologic stressors used with SPECT and confirmed that accuracy is near that of exercise SPECT. Patient-centered outcomes were reported in a meta-analysis of dipyridamole-thallium imaging in the preoperative evaluation of vascular surgery patients. The summary odds ratio for any perioperative cardiac event (in patients with abnormal tests) was 3.5 (95% confidence interval [CI], 2.5–4.8); the odds ratio for MI or cardiac death was 3.9 (95% CI, 2.5–5.6), leading the authors to conclude that there is sound evidence to use radionuclide testing in intermedi.ate-risk patients during preoperative screening.8
TABLE
Diagnostic accuracy reported in meta-analyses of cardiac radionuclide SPECT imaging
| Authors, year | Studies | Sn % (95% CI) | Sp % (95% CI) | LR+ | LR– |
|---|---|---|---|---|---|
| Garber and Solomon 19944 | 8 | 88 (73–98) | 77 (53–96) | 3.8 | 0.16 |
| Fleischmann et al, et al 19985 | 27 | 87 (86–88) | 64 (60–68) | 2.4 | 0.20 |
| Kwok et al, 19966 | 3 | 78 (69–87) | 58 (51–66) | 1.9 | 0.38 |
| Kim et al, 20017 | 44 | 90 (89–92)* | 75 (70–79)* | 3.6 | 0.13 |
| 89 (84–93)† | 65 (54–74)† | 2.5 | 0.17 | ||
| 82(77–87)‡ | 73 (70–79)‡ | 3.0 | 0.25 | ||
| *Adenosine SPECT | |||||
| †Dipyridamole SPECT | |||||
| ‡Dobutamine SPECT | |||||
| SPECT, single-photon emission computed tomography; SN, sensitivity; Sp, specifity; LR+, positive likelihood ratio; LR–, negative likelihood ratio; Cl, confidence interval | |||||
Recommendations from others
The American Heart Association/American College Cardiology (AHA/ACC) Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures and the American Society of Nuclear Cardiology updated guidelines for cardiac radionuclide imaging in 2003. In this consensus statement (a nonsystematic review of literature and expert opinion), they reported test characteristics to detect a 50% angiographic lesion as follows—exercise SPECT: sensitivity 87%, specificity 73%; vasodilator (adenosine or dipyridamole) SPECT: sensitivity 89%, specificity 75%. They noted that quantitative analysis performs as well as qualitative analysis of radionuclide images. Gated SPECT is slightly more specific and just as sensitive as nongated SPECT.
The Taskforce recommended that radionuclide perfusion scans be performed in patients with baseline electrocardiogram (ECG) abnormalities (such as left bundle branch block, hypertrophy, digitalis effect, etc), patients who cannot perform an exercise stress test, and to assess the functional effect of indeterminate lesions found on angiography. They also note that the repeat use of radionuclide testing 3 to 5 years after an event in asymptomatic high-risk patients and the initial use of radionuclide testing in patients at very high risk are both somewhat controversial, but the weight of limited evidence suggests some benefit to their use.9
ECG stress still the choice; image those with abnormal ECG or unable to exercise
David Kilgore, MD
Tacoma Family Medicine, Tacoma, Wash
Primary care providers frequently face the question of how best to evaluate patients with suspected CAD. Recent studies and expert opinion appear to give conflicting advice regarding the merits of plain exercise ECG vs stress imaging. Information on accuracy doesn’t always indicate which test is best for a patient.
Though quoted sensitivities and specificities for exercise ECG typically appear lower than those for stress imaging, costs for stress imaging are significantly higher, and numerous recent studies are demonstrating mortality outcome differences obtainable from physiologic information found in exercise testing (exercise capacity, blood pressure and pulse changes, time to angina).
Currently, the best choice for evaluation appears to be summarized by the 2003 AHA/ACC practice guidelines, which endorse exercise ECG for patients (women included) with intermediate pretest risk, and normal resting ECG for those who are unable to exercise. Stress imaging is cost effective for those patients with abnormal baseline ECG (left bundle branch block, ST abnormalities), or who are unable to exercise.
1. Detrano R, Janosi A, Lyons KP, Marcondes G, Abbassi N, Froelicher VF. Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram. Am J Med 1988;84:699-710.
2. Kotler TS, Diamond GA. Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. Ann Intern Med 1990;113:684-702.
3. Efficacy of exercise thallium-201 scintigraphy in diagnosis and prognosis of coronary artery disease. American College of Physicians. Ann Intern Med 1990;113:703-704.
4. Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 1999;130:719-728.
5. Fleischmann KE, Hunink MG, Kuntz KM, Douglas PS. Exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA 1998;280:913-920.
6. Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660-666.
7. Kim C, Kwok YS, Heagerty P, Redberg R. Pharmacologic stress testing for coronary artery disease diagnosis: A meta-analysis. Am Heart J 2001;142:934-944.
8. Shaw LJ, Eagle KA, Gersh BJ, Miller DD. Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985–1994) and dobutamine echocardiography (1991–1994) for risk stratification before vascular surgery. J Am Coll Cardiol 1996;27:787-798.
9. Klocke FJ, Baird MG, Bateman TM, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Radionuclide Imaging. Available at: www.acc.org/clinical/guidelines/radio/rni_fulltext.pdf. Accessed on December 14, 2003.
1. Detrano R, Janosi A, Lyons KP, Marcondes G, Abbassi N, Froelicher VF. Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram. Am J Med 1988;84:699-710.
2. Kotler TS, Diamond GA. Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. Ann Intern Med 1990;113:684-702.
3. Efficacy of exercise thallium-201 scintigraphy in diagnosis and prognosis of coronary artery disease. American College of Physicians. Ann Intern Med 1990;113:703-704.
4. Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 1999;130:719-728.
5. Fleischmann KE, Hunink MG, Kuntz KM, Douglas PS. Exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA 1998;280:913-920.
6. Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660-666.
7. Kim C, Kwok YS, Heagerty P, Redberg R. Pharmacologic stress testing for coronary artery disease diagnosis: A meta-analysis. Am Heart J 2001;142:934-944.
8. Shaw LJ, Eagle KA, Gersh BJ, Miller DD. Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985–1994) and dobutamine echocardiography (1991–1994) for risk stratification before vascular surgery. J Am Coll Cardiol 1996;27:787-798.
9. Klocke FJ, Baird MG, Bateman TM, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Radionuclide Imaging. Available at: www.acc.org/clinical/guidelines/radio/rni_fulltext.pdf. Accessed on December 14, 2003.
Evidence-based answers from the Family Physicians Inquiries Network
Losartan more effective than atenolol in hypertension with left ventricular hypertrophy
ABSTRACT
BACKGROUND: Left ventricular hypertrophy may be responsible for the higher risk of cardiovascular events that hypertensive patients suffer even after blood pressure reduction. Because angiotensin II is associated with the development of left ventricular hypertrophy, selective blockade of angiotensin II may reverse the hypertrophy and lead to decreased cardiovascular morbidity beyond just lowering blood pressure.
POPULATION STUDIED: A total of 9193 adults, aged 55 to 80 years, with hypertension (previously treated or untreated) and electrocardiographic (ECG) evidence of left ventricular hypertrophy were enrolled in the trial. Study participants were from Northern Europe and the United States; 54% were female and 92% were white. Patients with secondary hypertension, heart failure or left ventricular ejection fraction of 40% or less, history of myocardial infarction (MI) or stroke within the last 6 months, or angina pectoris requiring beta-blockers or calcium channel blockers were excluded. Also excluded were patients with disorders that required treatment with losartan or other angiotensin II type 1-receptor blockers, atenolol or other beta-blockers, hydrochlorothiazide, or angiotensin-converting enzyme (ACE) inhibitors.
STUDY DESIGN AND VALIDITY: After a run-in period with placebo, 9222 patients were randomized in a double-blind fashion to receive either losartan (50 mg daily) or atenolol (50 mg daily). Of these, 29 patients were excluded prior to group assignment and the remaining 9193 were included in an intention-to-treat analysis. The authors did not specifically state whether the treatment allocation process was concealed. In addition to either losartan or atenolol, patients were treated with hydrochlorothiazide and other antihypertensive medications as needed to obtain a blood pressure goal of less than 140/90 mm Hg. An independent clinical committee blinded to treatment group assignment determined the validity of all cardiovascular end points.
OUTCOMES MEASURED: The primary end point was cardiovascular morbidity and death, a composite end point consisting of stroke, MI, or cardiovascular death. The authors also measured individual cardiovascular events (stroke, MI, death) separately. Extensive data on blood pressure, use of additional medications, changes in ECG evidence of left ventricular hypertrophy, and adverse events were also compared.
RESULTS: Treatment groups had similar demographics, including baseline vital signs, ECG findings, cardiovascular risk scores, and mean arterial blood pressure on treatment. Patients in the losartan group had a significantly lower relative risk (RR) of the composite end point (stroke, MI, or cardiovascular death; RR = 0.87; 95% confidence interval [CI], 0.77–0.98; numbers needed to treat [NNT] = 244 patients per year). On individual outcomes, patients in the losartan group had a reduced risk of stroke (RR = 0.75; 95% CI, 0.63–0.89), but no statistically significant reduction in cardiovascular mortality (RR = 0.89; 95% CI, 0.73–.07), MI (RR = 1.07; 95% CI, 0.88–1.31) or all-cause mortality (RR = 0.90; 95% CI, 0.78–1.03).
Losartan may reduce cardiovascular morbidity and related deaths in hypertensive patients with documented left ventricular hypertrophy beyond that expected from only lowering blood pressure, especially through a reduction in stroke risk. However, this benefit was small in a select group of patients and no additional reduction was demonstrated in all-cause mortality compared with less expensive atenolol. The benefit of losartan over atenolol was more pronounced in a separate trial of hypertensive diabetic patients with left ventricular hypertrophy (NNT = 122 patients per year).1 Losartan was previously shown to be inferior to an ACE inhibitor agent (captopril) in the treatment of heart failure.2 Thus, there is no reason to believe that the benefit of losartan shown in this study is superior to (and may actually be less than) that of less expensive ACE inhibitors.
ABSTRACT
BACKGROUND: Left ventricular hypertrophy may be responsible for the higher risk of cardiovascular events that hypertensive patients suffer even after blood pressure reduction. Because angiotensin II is associated with the development of left ventricular hypertrophy, selective blockade of angiotensin II may reverse the hypertrophy and lead to decreased cardiovascular morbidity beyond just lowering blood pressure.
POPULATION STUDIED: A total of 9193 adults, aged 55 to 80 years, with hypertension (previously treated or untreated) and electrocardiographic (ECG) evidence of left ventricular hypertrophy were enrolled in the trial. Study participants were from Northern Europe and the United States; 54% were female and 92% were white. Patients with secondary hypertension, heart failure or left ventricular ejection fraction of 40% or less, history of myocardial infarction (MI) or stroke within the last 6 months, or angina pectoris requiring beta-blockers or calcium channel blockers were excluded. Also excluded were patients with disorders that required treatment with losartan or other angiotensin II type 1-receptor blockers, atenolol or other beta-blockers, hydrochlorothiazide, or angiotensin-converting enzyme (ACE) inhibitors.
STUDY DESIGN AND VALIDITY: After a run-in period with placebo, 9222 patients were randomized in a double-blind fashion to receive either losartan (50 mg daily) or atenolol (50 mg daily). Of these, 29 patients were excluded prior to group assignment and the remaining 9193 were included in an intention-to-treat analysis. The authors did not specifically state whether the treatment allocation process was concealed. In addition to either losartan or atenolol, patients were treated with hydrochlorothiazide and other antihypertensive medications as needed to obtain a blood pressure goal of less than 140/90 mm Hg. An independent clinical committee blinded to treatment group assignment determined the validity of all cardiovascular end points.
OUTCOMES MEASURED: The primary end point was cardiovascular morbidity and death, a composite end point consisting of stroke, MI, or cardiovascular death. The authors also measured individual cardiovascular events (stroke, MI, death) separately. Extensive data on blood pressure, use of additional medications, changes in ECG evidence of left ventricular hypertrophy, and adverse events were also compared.
RESULTS: Treatment groups had similar demographics, including baseline vital signs, ECG findings, cardiovascular risk scores, and mean arterial blood pressure on treatment. Patients in the losartan group had a significantly lower relative risk (RR) of the composite end point (stroke, MI, or cardiovascular death; RR = 0.87; 95% confidence interval [CI], 0.77–0.98; numbers needed to treat [NNT] = 244 patients per year). On individual outcomes, patients in the losartan group had a reduced risk of stroke (RR = 0.75; 95% CI, 0.63–0.89), but no statistically significant reduction in cardiovascular mortality (RR = 0.89; 95% CI, 0.73–.07), MI (RR = 1.07; 95% CI, 0.88–1.31) or all-cause mortality (RR = 0.90; 95% CI, 0.78–1.03).
Losartan may reduce cardiovascular morbidity and related deaths in hypertensive patients with documented left ventricular hypertrophy beyond that expected from only lowering blood pressure, especially through a reduction in stroke risk. However, this benefit was small in a select group of patients and no additional reduction was demonstrated in all-cause mortality compared with less expensive atenolol. The benefit of losartan over atenolol was more pronounced in a separate trial of hypertensive diabetic patients with left ventricular hypertrophy (NNT = 122 patients per year).1 Losartan was previously shown to be inferior to an ACE inhibitor agent (captopril) in the treatment of heart failure.2 Thus, there is no reason to believe that the benefit of losartan shown in this study is superior to (and may actually be less than) that of less expensive ACE inhibitors.
ABSTRACT
BACKGROUND: Left ventricular hypertrophy may be responsible for the higher risk of cardiovascular events that hypertensive patients suffer even after blood pressure reduction. Because angiotensin II is associated with the development of left ventricular hypertrophy, selective blockade of angiotensin II may reverse the hypertrophy and lead to decreased cardiovascular morbidity beyond just lowering blood pressure.
POPULATION STUDIED: A total of 9193 adults, aged 55 to 80 years, with hypertension (previously treated or untreated) and electrocardiographic (ECG) evidence of left ventricular hypertrophy were enrolled in the trial. Study participants were from Northern Europe and the United States; 54% were female and 92% were white. Patients with secondary hypertension, heart failure or left ventricular ejection fraction of 40% or less, history of myocardial infarction (MI) or stroke within the last 6 months, or angina pectoris requiring beta-blockers or calcium channel blockers were excluded. Also excluded were patients with disorders that required treatment with losartan or other angiotensin II type 1-receptor blockers, atenolol or other beta-blockers, hydrochlorothiazide, or angiotensin-converting enzyme (ACE) inhibitors.
STUDY DESIGN AND VALIDITY: After a run-in period with placebo, 9222 patients were randomized in a double-blind fashion to receive either losartan (50 mg daily) or atenolol (50 mg daily). Of these, 29 patients were excluded prior to group assignment and the remaining 9193 were included in an intention-to-treat analysis. The authors did not specifically state whether the treatment allocation process was concealed. In addition to either losartan or atenolol, patients were treated with hydrochlorothiazide and other antihypertensive medications as needed to obtain a blood pressure goal of less than 140/90 mm Hg. An independent clinical committee blinded to treatment group assignment determined the validity of all cardiovascular end points.
OUTCOMES MEASURED: The primary end point was cardiovascular morbidity and death, a composite end point consisting of stroke, MI, or cardiovascular death. The authors also measured individual cardiovascular events (stroke, MI, death) separately. Extensive data on blood pressure, use of additional medications, changes in ECG evidence of left ventricular hypertrophy, and adverse events were also compared.
RESULTS: Treatment groups had similar demographics, including baseline vital signs, ECG findings, cardiovascular risk scores, and mean arterial blood pressure on treatment. Patients in the losartan group had a significantly lower relative risk (RR) of the composite end point (stroke, MI, or cardiovascular death; RR = 0.87; 95% confidence interval [CI], 0.77–0.98; numbers needed to treat [NNT] = 244 patients per year). On individual outcomes, patients in the losartan group had a reduced risk of stroke (RR = 0.75; 95% CI, 0.63–0.89), but no statistically significant reduction in cardiovascular mortality (RR = 0.89; 95% CI, 0.73–.07), MI (RR = 1.07; 95% CI, 0.88–1.31) or all-cause mortality (RR = 0.90; 95% CI, 0.78–1.03).
Losartan may reduce cardiovascular morbidity and related deaths in hypertensive patients with documented left ventricular hypertrophy beyond that expected from only lowering blood pressure, especially through a reduction in stroke risk. However, this benefit was small in a select group of patients and no additional reduction was demonstrated in all-cause mortality compared with less expensive atenolol. The benefit of losartan over atenolol was more pronounced in a separate trial of hypertensive diabetic patients with left ventricular hypertrophy (NNT = 122 patients per year).1 Losartan was previously shown to be inferior to an ACE inhibitor agent (captopril) in the treatment of heart failure.2 Thus, there is no reason to believe that the benefit of losartan shown in this study is superior to (and may actually be less than) that of less expensive ACE inhibitors.
What is the best way to evaluate acute diarrhea?
Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease. (Grade of recommendation: D, based on limited studies, reliance on expert opinion, and consensus.)
Evidence summary
More than 2 million cases of infectious diarrhea are documented in the United States annually. Infectious diarrhea is the second leading cause of morbidity and mortality worldwide. Published data have focused on the etiology of diarrhea in the developing world, and more commonly on the clinical evaluation and treatment of patients with diarrhea and dehydration.
While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered (eg, drug-induced diarrhea, inflammatory bowel disease).1 Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea.2 A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases (Table).3
A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus.4 A recent systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea.5
Some evidence supports a structured diagnostic strategy for hospitalized patients with acute diarrhea. Using retrospective reviews, Bauer and colleagues6 developed a prediction rule for cases of infectious diarrhea. The “modified 3-day rule” recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection.6 When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment.6
TABLE 1
Etiologic agents in US children with acute diarrhea
| Infectious agent | Percent |
|---|---|
| Rotavirus | 29.3% |
| Giardia lamblia | 15% |
| Pathogenic Escherichia coli | 15% |
| Multiple agents | 10% |
| Data from Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999; 18:94–7. | |
Recommendations from others
The Infectious Diseases Society of America’s practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria (including enterotoxic E coli) should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days.1
Clinical Commentary by Les Hall, MD, at http://www.fpin.org.
1. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
2. Merrick N, Davidson B, Fox S. Treatment of acute gastroenteritis: too much and too little care. Clin Pediatr (Phila) 1996;35:429-35.
3. Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999;18:94-7.
4. Nakajima H, Nakagomi T, Kamisawa T, et al. Winter seasonality and rotavirus diarrhoea in adults. Lancet 2001;357(9272):1950.-
5. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.
6. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001;285:313-9.
Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease. (Grade of recommendation: D, based on limited studies, reliance on expert opinion, and consensus.)
Evidence summary
More than 2 million cases of infectious diarrhea are documented in the United States annually. Infectious diarrhea is the second leading cause of morbidity and mortality worldwide. Published data have focused on the etiology of diarrhea in the developing world, and more commonly on the clinical evaluation and treatment of patients with diarrhea and dehydration.
While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered (eg, drug-induced diarrhea, inflammatory bowel disease).1 Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea.2 A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases (Table).3
A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus.4 A recent systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea.5
Some evidence supports a structured diagnostic strategy for hospitalized patients with acute diarrhea. Using retrospective reviews, Bauer and colleagues6 developed a prediction rule for cases of infectious diarrhea. The “modified 3-day rule” recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection.6 When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment.6
TABLE 1
Etiologic agents in US children with acute diarrhea
| Infectious agent | Percent |
|---|---|
| Rotavirus | 29.3% |
| Giardia lamblia | 15% |
| Pathogenic Escherichia coli | 15% |
| Multiple agents | 10% |
| Data from Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999; 18:94–7. | |
Recommendations from others
The Infectious Diseases Society of America’s practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria (including enterotoxic E coli) should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days.1
Clinical Commentary by Les Hall, MD, at http://www.fpin.org.
Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease. (Grade of recommendation: D, based on limited studies, reliance on expert opinion, and consensus.)
Evidence summary
More than 2 million cases of infectious diarrhea are documented in the United States annually. Infectious diarrhea is the second leading cause of morbidity and mortality worldwide. Published data have focused on the etiology of diarrhea in the developing world, and more commonly on the clinical evaluation and treatment of patients with diarrhea and dehydration.
While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered (eg, drug-induced diarrhea, inflammatory bowel disease).1 Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea.2 A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases (Table).3
A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus.4 A recent systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea.5
Some evidence supports a structured diagnostic strategy for hospitalized patients with acute diarrhea. Using retrospective reviews, Bauer and colleagues6 developed a prediction rule for cases of infectious diarrhea. The “modified 3-day rule” recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection.6 When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment.6
TABLE 1
Etiologic agents in US children with acute diarrhea
| Infectious agent | Percent |
|---|---|
| Rotavirus | 29.3% |
| Giardia lamblia | 15% |
| Pathogenic Escherichia coli | 15% |
| Multiple agents | 10% |
| Data from Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999; 18:94–7. | |
Recommendations from others
The Infectious Diseases Society of America’s practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria (including enterotoxic E coli) should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days.1
Clinical Commentary by Les Hall, MD, at http://www.fpin.org.
1. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
2. Merrick N, Davidson B, Fox S. Treatment of acute gastroenteritis: too much and too little care. Clin Pediatr (Phila) 1996;35:429-35.
3. Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999;18:94-7.
4. Nakajima H, Nakagomi T, Kamisawa T, et al. Winter seasonality and rotavirus diarrhoea in adults. Lancet 2001;357(9272):1950.-
5. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.
6. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001;285:313-9.
1. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
2. Merrick N, Davidson B, Fox S. Treatment of acute gastroenteritis: too much and too little care. Clin Pediatr (Phila) 1996;35:429-35.
3. Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999;18:94-7.
4. Nakajima H, Nakagomi T, Kamisawa T, et al. Winter seasonality and rotavirus diarrhoea in adults. Lancet 2001;357(9272):1950.-
5. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.
6. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001;285:313-9.
Evidence-based answers from the Family Physicians Inquiries Network
Are angiotensin-converting enzyme (ACE) inhibitors effective in preventing migraine in nonhypertensive patients?
BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.
POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.
STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.
OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.
RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.
This well-designed study of lisinopril for moderate migraine sufferers suggests that another class of medications may be beneficial for prophylaxis. Though a relatively modest decrease in headaches was reported and there was wide variability in the results, lisinopril was well tolerated and has advantages over current prophylactic medications. A certain subset of patients responded very well to treatment. For patients with frequent migraines who have not responded to other prophylactic medications, a trial of ACE inhibitors may be useful.
BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.
POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.
STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.
OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.
RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.
This well-designed study of lisinopril for moderate migraine sufferers suggests that another class of medications may be beneficial for prophylaxis. Though a relatively modest decrease in headaches was reported and there was wide variability in the results, lisinopril was well tolerated and has advantages over current prophylactic medications. A certain subset of patients responded very well to treatment. For patients with frequent migraines who have not responded to other prophylactic medications, a trial of ACE inhibitors may be useful.
BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.
POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.
STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.
OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.
RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.
This well-designed study of lisinopril for moderate migraine sufferers suggests that another class of medications may be beneficial for prophylaxis. Though a relatively modest decrease in headaches was reported and there was wide variability in the results, lisinopril was well tolerated and has advantages over current prophylactic medications. A certain subset of patients responded very well to treatment. For patients with frequent migraines who have not responded to other prophylactic medications, a trial of ACE inhibitors may be useful.