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Does early detection of suspected atherosclerotic renovascular hypertension change outcomes?
We found no evidence for changed outcomes from early detection of renal artery stenosis (RAS). Treatment of RAS in refractory hypertension modestly improves blood pressure control. There was a trend toward improved clinical outcomes but studies were underpowered to demonstrate this (strength of recommendation [SOR]: A, based on systematic review of RCTs).
Treatment of RAS in chronic renal impairment does not appear to improve renal function nor change clinical outcomes, but data are conflicting (SOR: A, based on 2 RCTs and multiple cohort studies). Subgroups of patients who have recurrent episodes of congestive heart failure or flash pulmonary edema exhibit functional improvement following percutaneous transluminal renal angioplasty (PTRA) with stent placement. (SOR: C, based on a retrospective cohort study).
Computed tomography (CT) angiography and magnetic resonance angiography (MRA) are the most accurate and cost-effective noninterventional diagnostic modalities for RAS (SOR: A, based on a large meta-analysis).
While revascularization effectively improves patency, the complication rate is high and deaths have occurred (SOR: B, based on randomized controlled trials [RCTs]). Patients with worse renal function tend to do more poorly (SOR: C, based on retrospective cohort studies). Data are insufficient to recommend a method of revascularization (surgical vs PTRA with or without stenting) (SOR: C, based on multiple cohort studies).
When herding hypertensives, treat them all like horses, not zebras
Dan Triezenberg, MD
Family Practice Residency, Saint Joseph Regional Medical Center, South Bend, Ind
“When you hear hoofbeats, think of horses. You will occasionally see a zebra and very rarely a unicorn.” Patients who benefit from physicians looking for and treating renovascular hypertension are unicorns, not zebras. A very few patients benefit by needing fewer drugs, while a few are harmed by complications of revascularization. No benefit in overall mortality, disease specific mortality or vascular morbidity (stroke, heart disease) has been demonstrated. So, the take-home message is: When herding hypertensives, treat them all like horses—you may stumble across a few zebras, but looking for benefit from discovering and treating renovascular hypertension is as fruitful as looking for unicorns—a product of imagination, myth, and hope, not based in reality. Based on this Clinical Inquiry, I will stop feeling guilty about not searching diligently for renovascular causes of “curable hypertension.”
Evidence summary
“Early” diagnosis of renovascular hypertension is best defined as diagnosis while blood pressure is controlled by medications or when renal function remains normal.
Hypertension. A meta-analysis (3 RCTs, total n=210 patients) examining balloon angioplasty for RAS and poorly controlled hypertension showed modest but significant effect on blood pressure control.1 Comparing the angioplasty group with medical management, the mean reduction in blood pressure was –7 mm Hg systolic (95% confidence interval [CI], –12 to –1) and –3 mm Hg diastolic (95% CI, –6 to –1). Patients treated with balloon angioplasty were more likely to use fewer antihypertensive medications (unable to synthesize data for quantity) and to have fewer major cardiovascular and renovascular complications (not defined specifically) (odds ratio [OR]=0.27; 95% CI, 0.06–1.23; P=.09).1 One cohort study of 150 patients found that stenting bilateral (vs unilateral) RAS predicted a more beneficial blood pressure response (OR=4.6; P=.009).2
Renal impairment. The value of RAS intervention for patients with hypertension and worsening renal function is unclear. One RCT of 106 patients with atherosclerotic RAS and serum creatinine (Cr) of <2.3 mg/dL compared PTRA with medical therapy of hypertension. By an intentionto-treat analysis, there was no significant difference in renal function at 12 months between the groups.3 A nonblinded RCT of 85 patients found no change in mortality or renal function with intervention. Three groups were compared: observation of 52 patients with unilateral RAS (>50%), intervention on 12 patients with bilateral RAS, and observation of 21 patients with bilateral RAS. All groups reported 32% mortality at 2 years. Only 3 of the 27 deaths were directly related to renal disease (2 from the observation group with unilateral RAS and one from the intervention group).4 Cohor studies, using different measures of renal function, report improvement, stabilization, or worsening following intervention.5-7
Congestive heart failure and flash pulmonary edema. Patients who have recurrent episodes of congestive heart failure or flash pulmonary edema with severe RAS have marked functional improvement following PTRA with stenting. One retrospective cohort study (n=39) reported a decrease in hospitalizations (from 2.4 ±1.4 per year to 0.3 ±0.7 per year; P<.001) and improvement in New York Heart Association heart failure functional classification (2.9 ±0.9 to 1.6 ±0.9).8
Diagnosis. MRA (sensitivity 99%, specificity 93%) and CT angiography (sensitivity 97%, specificity 95%) are the most accurate and cost-effective, based on a large meta-analysis.9
Complications. Serious or potentially serious complications (ie, bleeding, renal artery injury, need for hemodialysis) were seen in 13% to 25% of patients who underwent angioplasty.2,5,7 Combining 3 studies (n=632), there were 5 procedurerelated deaths.5,7,10
Worsened patient survival correlated with Cr >1.7 mg/dL or age >70 (OR=9.96, P<.0001 and OR=3.4, P=.001, respectively). Worsened renal survival was present in the same subgroups (OR=7.8, P<.001 and OR=2.7, P<.01, respectively).7
Recommendations from others
The American Heart Association lists 3 clinical criteria for revascularization: 1) hypertension (accelerated, refractory, or malignant), 2) renal salvage, 3) cardiac disturbance syndromes (recurrent “flash” pulmonary edema or unstable angina with significant RAS).11 JNC 7 does not recommend looking for RAS unless hypertension is uncontrollable.12
The Society of Nuclear Medicine recommends that only moderate- to high-risk individuals be screened for RAS. This guideline clarifies that RAS does not equal renovascular hypertension and that the future “gold standard” diagnosis of renovascular hypertension should be the response to successful revascularization.13
1. Nordmann AJ, Woo K, Parkes R, Logan AG. Balloon angioplasty or medical therapy for hypertensive patients with atherosclerotic renal artery stenosis? A meta-analysis of randomized controlled trials. Am J Med 2003;114:44-50.
2. Zeller T, Frank U, Muller C, et al. Stent-supported angioplasty of severe atherosclerotic renal artery stenosis preserves renal function and improves blood pressure control: long-term results from a prospective registry of 456 lesions. J Endovasc Ther 2004;11:95-106.
3. Van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renalartery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group. N Engl J Med 2000;342:1007-1014.
4. Pillay WR, Kan Y, Crinnion J, Wolfe J. Prospective multicentre study of the natural history of atherosclerotic RAS in patients with peripheral vascular disease. Br J Surg 2002;89:737-740.
5. Rundback JH, Manoni T, Rozenblit GN, et al. Balloon angioplasty or stent placement in patients with azotemic renovascular disease: a retrospective comparison of clinical outcomes. Heart Dis 1999;1:121-125.
6. Lederman RJ, Mendelsohn FO, Santos R, Phillips HR, Stack RS, Crowley JJ. Primary renal artery stenting: characteristics and outcomes after 363 procedures. Am Heart J 2001;142:314-323.
7. Perkovi V, Thomson KR, Becker GJ. Factors affecting outcome after percutaneous renal artery stent insertion. J Nephrol 2002;15:649-654.
8. Gray BH, Olin JW, Childs MB, Sullivan TM, Bacharach JM. Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure. Vasc Med 2002;7:275-279.
9. Vasbinder C, Nelemans P, Kessels AGH, Kroon AA, de Leeuw PW, van Engelshoven JM. Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: a meta-analysis. Ann Intern Med 2001;135:401-411.
10. Isles CG, Robertson S, Hill D. Management of renovascular disease: a review of renal artery stenting in ten studies. QJM 1999;92:159-167.
11. Rundback JH, Sacks D, Kent KC, et al. American Heart Association. Guidelines for the reporting of renal artery revascularization in clinical trials. Circulation 2002;106:1572.-
12. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003;289:2560-2571.
13. Taylor AT, Jr, Blaufox MD, Dubovsky EV, et al. Procedure guideline for diagnosis of renovascular hypertension, 3.0. Reston,Va: Society of Nuclear Medicine; 2003.
We found no evidence for changed outcomes from early detection of renal artery stenosis (RAS). Treatment of RAS in refractory hypertension modestly improves blood pressure control. There was a trend toward improved clinical outcomes but studies were underpowered to demonstrate this (strength of recommendation [SOR]: A, based on systematic review of RCTs).
Treatment of RAS in chronic renal impairment does not appear to improve renal function nor change clinical outcomes, but data are conflicting (SOR: A, based on 2 RCTs and multiple cohort studies). Subgroups of patients who have recurrent episodes of congestive heart failure or flash pulmonary edema exhibit functional improvement following percutaneous transluminal renal angioplasty (PTRA) with stent placement. (SOR: C, based on a retrospective cohort study).
Computed tomography (CT) angiography and magnetic resonance angiography (MRA) are the most accurate and cost-effective noninterventional diagnostic modalities for RAS (SOR: A, based on a large meta-analysis).
While revascularization effectively improves patency, the complication rate is high and deaths have occurred (SOR: B, based on randomized controlled trials [RCTs]). Patients with worse renal function tend to do more poorly (SOR: C, based on retrospective cohort studies). Data are insufficient to recommend a method of revascularization (surgical vs PTRA with or without stenting) (SOR: C, based on multiple cohort studies).
When herding hypertensives, treat them all like horses, not zebras
Dan Triezenberg, MD
Family Practice Residency, Saint Joseph Regional Medical Center, South Bend, Ind
“When you hear hoofbeats, think of horses. You will occasionally see a zebra and very rarely a unicorn.” Patients who benefit from physicians looking for and treating renovascular hypertension are unicorns, not zebras. A very few patients benefit by needing fewer drugs, while a few are harmed by complications of revascularization. No benefit in overall mortality, disease specific mortality or vascular morbidity (stroke, heart disease) has been demonstrated. So, the take-home message is: When herding hypertensives, treat them all like horses—you may stumble across a few zebras, but looking for benefit from discovering and treating renovascular hypertension is as fruitful as looking for unicorns—a product of imagination, myth, and hope, not based in reality. Based on this Clinical Inquiry, I will stop feeling guilty about not searching diligently for renovascular causes of “curable hypertension.”
Evidence summary
“Early” diagnosis of renovascular hypertension is best defined as diagnosis while blood pressure is controlled by medications or when renal function remains normal.
Hypertension. A meta-analysis (3 RCTs, total n=210 patients) examining balloon angioplasty for RAS and poorly controlled hypertension showed modest but significant effect on blood pressure control.1 Comparing the angioplasty group with medical management, the mean reduction in blood pressure was –7 mm Hg systolic (95% confidence interval [CI], –12 to –1) and –3 mm Hg diastolic (95% CI, –6 to –1). Patients treated with balloon angioplasty were more likely to use fewer antihypertensive medications (unable to synthesize data for quantity) and to have fewer major cardiovascular and renovascular complications (not defined specifically) (odds ratio [OR]=0.27; 95% CI, 0.06–1.23; P=.09).1 One cohort study of 150 patients found that stenting bilateral (vs unilateral) RAS predicted a more beneficial blood pressure response (OR=4.6; P=.009).2
Renal impairment. The value of RAS intervention for patients with hypertension and worsening renal function is unclear. One RCT of 106 patients with atherosclerotic RAS and serum creatinine (Cr) of <2.3 mg/dL compared PTRA with medical therapy of hypertension. By an intentionto-treat analysis, there was no significant difference in renal function at 12 months between the groups.3 A nonblinded RCT of 85 patients found no change in mortality or renal function with intervention. Three groups were compared: observation of 52 patients with unilateral RAS (>50%), intervention on 12 patients with bilateral RAS, and observation of 21 patients with bilateral RAS. All groups reported 32% mortality at 2 years. Only 3 of the 27 deaths were directly related to renal disease (2 from the observation group with unilateral RAS and one from the intervention group).4 Cohor studies, using different measures of renal function, report improvement, stabilization, or worsening following intervention.5-7
Congestive heart failure and flash pulmonary edema. Patients who have recurrent episodes of congestive heart failure or flash pulmonary edema with severe RAS have marked functional improvement following PTRA with stenting. One retrospective cohort study (n=39) reported a decrease in hospitalizations (from 2.4 ±1.4 per year to 0.3 ±0.7 per year; P<.001) and improvement in New York Heart Association heart failure functional classification (2.9 ±0.9 to 1.6 ±0.9).8
Diagnosis. MRA (sensitivity 99%, specificity 93%) and CT angiography (sensitivity 97%, specificity 95%) are the most accurate and cost-effective, based on a large meta-analysis.9
Complications. Serious or potentially serious complications (ie, bleeding, renal artery injury, need for hemodialysis) were seen in 13% to 25% of patients who underwent angioplasty.2,5,7 Combining 3 studies (n=632), there were 5 procedurerelated deaths.5,7,10
Worsened patient survival correlated with Cr >1.7 mg/dL or age >70 (OR=9.96, P<.0001 and OR=3.4, P=.001, respectively). Worsened renal survival was present in the same subgroups (OR=7.8, P<.001 and OR=2.7, P<.01, respectively).7
Recommendations from others
The American Heart Association lists 3 clinical criteria for revascularization: 1) hypertension (accelerated, refractory, or malignant), 2) renal salvage, 3) cardiac disturbance syndromes (recurrent “flash” pulmonary edema or unstable angina with significant RAS).11 JNC 7 does not recommend looking for RAS unless hypertension is uncontrollable.12
The Society of Nuclear Medicine recommends that only moderate- to high-risk individuals be screened for RAS. This guideline clarifies that RAS does not equal renovascular hypertension and that the future “gold standard” diagnosis of renovascular hypertension should be the response to successful revascularization.13
We found no evidence for changed outcomes from early detection of renal artery stenosis (RAS). Treatment of RAS in refractory hypertension modestly improves blood pressure control. There was a trend toward improved clinical outcomes but studies were underpowered to demonstrate this (strength of recommendation [SOR]: A, based on systematic review of RCTs).
Treatment of RAS in chronic renal impairment does not appear to improve renal function nor change clinical outcomes, but data are conflicting (SOR: A, based on 2 RCTs and multiple cohort studies). Subgroups of patients who have recurrent episodes of congestive heart failure or flash pulmonary edema exhibit functional improvement following percutaneous transluminal renal angioplasty (PTRA) with stent placement. (SOR: C, based on a retrospective cohort study).
Computed tomography (CT) angiography and magnetic resonance angiography (MRA) are the most accurate and cost-effective noninterventional diagnostic modalities for RAS (SOR: A, based on a large meta-analysis).
While revascularization effectively improves patency, the complication rate is high and deaths have occurred (SOR: B, based on randomized controlled trials [RCTs]). Patients with worse renal function tend to do more poorly (SOR: C, based on retrospective cohort studies). Data are insufficient to recommend a method of revascularization (surgical vs PTRA with or without stenting) (SOR: C, based on multiple cohort studies).
When herding hypertensives, treat them all like horses, not zebras
Dan Triezenberg, MD
Family Practice Residency, Saint Joseph Regional Medical Center, South Bend, Ind
“When you hear hoofbeats, think of horses. You will occasionally see a zebra and very rarely a unicorn.” Patients who benefit from physicians looking for and treating renovascular hypertension are unicorns, not zebras. A very few patients benefit by needing fewer drugs, while a few are harmed by complications of revascularization. No benefit in overall mortality, disease specific mortality or vascular morbidity (stroke, heart disease) has been demonstrated. So, the take-home message is: When herding hypertensives, treat them all like horses—you may stumble across a few zebras, but looking for benefit from discovering and treating renovascular hypertension is as fruitful as looking for unicorns—a product of imagination, myth, and hope, not based in reality. Based on this Clinical Inquiry, I will stop feeling guilty about not searching diligently for renovascular causes of “curable hypertension.”
Evidence summary
“Early” diagnosis of renovascular hypertension is best defined as diagnosis while blood pressure is controlled by medications or when renal function remains normal.
Hypertension. A meta-analysis (3 RCTs, total n=210 patients) examining balloon angioplasty for RAS and poorly controlled hypertension showed modest but significant effect on blood pressure control.1 Comparing the angioplasty group with medical management, the mean reduction in blood pressure was –7 mm Hg systolic (95% confidence interval [CI], –12 to –1) and –3 mm Hg diastolic (95% CI, –6 to –1). Patients treated with balloon angioplasty were more likely to use fewer antihypertensive medications (unable to synthesize data for quantity) and to have fewer major cardiovascular and renovascular complications (not defined specifically) (odds ratio [OR]=0.27; 95% CI, 0.06–1.23; P=.09).1 One cohort study of 150 patients found that stenting bilateral (vs unilateral) RAS predicted a more beneficial blood pressure response (OR=4.6; P=.009).2
Renal impairment. The value of RAS intervention for patients with hypertension and worsening renal function is unclear. One RCT of 106 patients with atherosclerotic RAS and serum creatinine (Cr) of <2.3 mg/dL compared PTRA with medical therapy of hypertension. By an intentionto-treat analysis, there was no significant difference in renal function at 12 months between the groups.3 A nonblinded RCT of 85 patients found no change in mortality or renal function with intervention. Three groups were compared: observation of 52 patients with unilateral RAS (>50%), intervention on 12 patients with bilateral RAS, and observation of 21 patients with bilateral RAS. All groups reported 32% mortality at 2 years. Only 3 of the 27 deaths were directly related to renal disease (2 from the observation group with unilateral RAS and one from the intervention group).4 Cohor studies, using different measures of renal function, report improvement, stabilization, or worsening following intervention.5-7
Congestive heart failure and flash pulmonary edema. Patients who have recurrent episodes of congestive heart failure or flash pulmonary edema with severe RAS have marked functional improvement following PTRA with stenting. One retrospective cohort study (n=39) reported a decrease in hospitalizations (from 2.4 ±1.4 per year to 0.3 ±0.7 per year; P<.001) and improvement in New York Heart Association heart failure functional classification (2.9 ±0.9 to 1.6 ±0.9).8
Diagnosis. MRA (sensitivity 99%, specificity 93%) and CT angiography (sensitivity 97%, specificity 95%) are the most accurate and cost-effective, based on a large meta-analysis.9
Complications. Serious or potentially serious complications (ie, bleeding, renal artery injury, need for hemodialysis) were seen in 13% to 25% of patients who underwent angioplasty.2,5,7 Combining 3 studies (n=632), there were 5 procedurerelated deaths.5,7,10
Worsened patient survival correlated with Cr >1.7 mg/dL or age >70 (OR=9.96, P<.0001 and OR=3.4, P=.001, respectively). Worsened renal survival was present in the same subgroups (OR=7.8, P<.001 and OR=2.7, P<.01, respectively).7
Recommendations from others
The American Heart Association lists 3 clinical criteria for revascularization: 1) hypertension (accelerated, refractory, or malignant), 2) renal salvage, 3) cardiac disturbance syndromes (recurrent “flash” pulmonary edema or unstable angina with significant RAS).11 JNC 7 does not recommend looking for RAS unless hypertension is uncontrollable.12
The Society of Nuclear Medicine recommends that only moderate- to high-risk individuals be screened for RAS. This guideline clarifies that RAS does not equal renovascular hypertension and that the future “gold standard” diagnosis of renovascular hypertension should be the response to successful revascularization.13
1. Nordmann AJ, Woo K, Parkes R, Logan AG. Balloon angioplasty or medical therapy for hypertensive patients with atherosclerotic renal artery stenosis? A meta-analysis of randomized controlled trials. Am J Med 2003;114:44-50.
2. Zeller T, Frank U, Muller C, et al. Stent-supported angioplasty of severe atherosclerotic renal artery stenosis preserves renal function and improves blood pressure control: long-term results from a prospective registry of 456 lesions. J Endovasc Ther 2004;11:95-106.
3. Van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renalartery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group. N Engl J Med 2000;342:1007-1014.
4. Pillay WR, Kan Y, Crinnion J, Wolfe J. Prospective multicentre study of the natural history of atherosclerotic RAS in patients with peripheral vascular disease. Br J Surg 2002;89:737-740.
5. Rundback JH, Manoni T, Rozenblit GN, et al. Balloon angioplasty or stent placement in patients with azotemic renovascular disease: a retrospective comparison of clinical outcomes. Heart Dis 1999;1:121-125.
6. Lederman RJ, Mendelsohn FO, Santos R, Phillips HR, Stack RS, Crowley JJ. Primary renal artery stenting: characteristics and outcomes after 363 procedures. Am Heart J 2001;142:314-323.
7. Perkovi V, Thomson KR, Becker GJ. Factors affecting outcome after percutaneous renal artery stent insertion. J Nephrol 2002;15:649-654.
8. Gray BH, Olin JW, Childs MB, Sullivan TM, Bacharach JM. Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure. Vasc Med 2002;7:275-279.
9. Vasbinder C, Nelemans P, Kessels AGH, Kroon AA, de Leeuw PW, van Engelshoven JM. Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: a meta-analysis. Ann Intern Med 2001;135:401-411.
10. Isles CG, Robertson S, Hill D. Management of renovascular disease: a review of renal artery stenting in ten studies. QJM 1999;92:159-167.
11. Rundback JH, Sacks D, Kent KC, et al. American Heart Association. Guidelines for the reporting of renal artery revascularization in clinical trials. Circulation 2002;106:1572.-
12. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003;289:2560-2571.
13. Taylor AT, Jr, Blaufox MD, Dubovsky EV, et al. Procedure guideline for diagnosis of renovascular hypertension, 3.0. Reston,Va: Society of Nuclear Medicine; 2003.
1. Nordmann AJ, Woo K, Parkes R, Logan AG. Balloon angioplasty or medical therapy for hypertensive patients with atherosclerotic renal artery stenosis? A meta-analysis of randomized controlled trials. Am J Med 2003;114:44-50.
2. Zeller T, Frank U, Muller C, et al. Stent-supported angioplasty of severe atherosclerotic renal artery stenosis preserves renal function and improves blood pressure control: long-term results from a prospective registry of 456 lesions. J Endovasc Ther 2004;11:95-106.
3. Van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renalartery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group. N Engl J Med 2000;342:1007-1014.
4. Pillay WR, Kan Y, Crinnion J, Wolfe J. Prospective multicentre study of the natural history of atherosclerotic RAS in patients with peripheral vascular disease. Br J Surg 2002;89:737-740.
5. Rundback JH, Manoni T, Rozenblit GN, et al. Balloon angioplasty or stent placement in patients with azotemic renovascular disease: a retrospective comparison of clinical outcomes. Heart Dis 1999;1:121-125.
6. Lederman RJ, Mendelsohn FO, Santos R, Phillips HR, Stack RS, Crowley JJ. Primary renal artery stenting: characteristics and outcomes after 363 procedures. Am Heart J 2001;142:314-323.
7. Perkovi V, Thomson KR, Becker GJ. Factors affecting outcome after percutaneous renal artery stent insertion. J Nephrol 2002;15:649-654.
8. Gray BH, Olin JW, Childs MB, Sullivan TM, Bacharach JM. Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure. Vasc Med 2002;7:275-279.
9. Vasbinder C, Nelemans P, Kessels AGH, Kroon AA, de Leeuw PW, van Engelshoven JM. Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: a meta-analysis. Ann Intern Med 2001;135:401-411.
10. Isles CG, Robertson S, Hill D. Management of renovascular disease: a review of renal artery stenting in ten studies. QJM 1999;92:159-167.
11. Rundback JH, Sacks D, Kent KC, et al. American Heart Association. Guidelines for the reporting of renal artery revascularization in clinical trials. Circulation 2002;106:1572.-
12. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003;289:2560-2571.
13. Taylor AT, Jr, Blaufox MD, Dubovsky EV, et al. Procedure guideline for diagnosis of renovascular hypertension, 3.0. Reston,Va: Society of Nuclear Medicine; 2003.
Evidence-based answers from the Family Physicians Inquiries Network
Other than anticoagulation, what is the best therapy for those with atrial fibrillation?
Rate control with long-term anticoagulation is recommended for most patients with atrial fibrillation (strength of recommendation [SOR]: A, based on randomized controlled trials [RCTs]). A rhythmcontrol strategy provides no survival or quality-of-life benefit when compared with rate control and causes more adverse drug effects and increased hospitalizations (SOR: A, based on RCTs).
Non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) and most beta-blockers are effective for controlling heart rate both at rest and during exercise (SOR: A, based on RCTs). Digoxin is only effective for rate control at rest and should be reserved for patients with systolic dysfunction or as an adjunct for those inadequately rate-controlled on calcium-channel blockers or beta-blockers (SOR: B, based on RCTs).
Subgroups in whom rhythm control may be superior are patients with persistent fatigue and dyspnea despite ventricular rate control and those unable to achieve adequate rate control. Both pharmacologic conversion (SOR: B, based on RCTs) and direct-current cardioversion (SOR: B, based on observational studies) are appropriate options in these patients.
Long-term anticoagulation is necessary for high-risk patients even if they are successfully managed with rhythm control (SOR: A, based on RCTs).
Evidence summary
Five recent RCTs have demonstrated similar mortality and cardiovascular morbidity in atrial fibrillation patients treated with either a rate-control or rhythm-control strategy.1-5
The AFFIRM trial, the largest (n=4060), was a nonblinded, randomized, multicenter study with an average follow-up of 3.5 years.1 The patients were aged 65 years or older and had at least 1 other risk factor for stroke. The rhythm-control group was given an antiarrhythmic medication chosen by the treating physician, while the rate-control group was given either a beta-blocker, a calcium-channel blocker, digoxin, or a combination of these as needed. Heart-rate goals were a resting pulse under 80 beats per minute, and a pulse after a 6-minute walk under 110 beats per minute. An intention-totreat analysis was followed.
There was no difference between the 2 groups for the composite endpoints of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest. A nonsignificant trend was observed for mortality favoring the rate-control group (relative risk [RR]=1.15; 95% confidence interval [CI], 0.99–1.34). Quality-of-life measures were equivalent in the 2 groups at all points in the study.1
More patients in the rhythm-control group required hospitalization (number needed to harm [NNH]=12.3; P<.001) and had adverse drug effects (P.001 for each of pulmonary events [NNH=18], gastrointestinal events [NNH=17], bradycardia [NNH=56], and prolonged QT [NNH=63]). This trial did not include younger patients without stroke risk factors, or those with paroxysmal atrial fibrillation.1
The 4 other RCTs also found no greater benefit with a rhythm-control strategy vs rate-control for most patients with atrial fibrillation.2-5
Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation.6,7 The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo.6,7
All beta-blockers tested were effective in rate-control during exercise and most (excluding labetalol and celiprolol) were effective at rest.6,7 Digoxin was ineffective during exercise and less effective than beta-blockers or calcium-channel blockers at rest.6-8 The combination of digoxin plus a calcium-channel blocker or beta-blocker may have increased benefit compared with either drug alone.6 Evidence was insufficient to recommend propafenone, clonidine, or amiodarone for rate control.7
In select patients, a rhythm-control approach may be desirable. A meta-analysis of 60 RCTs evaluated 8 drugs for acute cardioversion. Ibutilide, flecainide, dofetilide, propafenone, and amiodarone were found to have the strongest evidence of efficacy.6 There was moderate evidence for quinidine and insufficient evidence for disopyramide and sotalol.6 Studies of pharmacologic conversion suffer from small ample size, short follow-up, and variable duration of atrial fibrillation.6 A review of limited research reveals an 80% to 85% immediate success rate for DC cardioversion, with rare side-effects of ventricular tachycardia, transient AV node dysfunction, and significant skin blistering.6
For patients who elect a rhythm-control approach, RCTs demonstrate the need for continued long-term anticoagulation in high-risk patients even if they are maintained in sinus rhythm.1,4,5 (High-risk patients are defined as those aged >65 years, or those <65 years with 1 or more stroke risk factors: diabetes, hypertension, heart failure, prior transient ischemic attack or stroke or systemic embolism, or echocardiographic evidence of a left atrium >50 mm, a shortening fraction <25%, or an ejection fraction <40%.)
Recommendation from others
The American Academy of Family Practice/American College of Physicians’ clinical guidelines support a rate-control strategy for most patients with atrial fibrillation and recommend atenolol, metoprolol, diltiazem, or verapamil as the first-choice drugs.8 Digoxin is recommended as a second-line agent. DC cardioversion and pharmacologic conversion for patients who desire a rhythm-control strategy are described as “appropriate options.”8
Rate control best for atrial fibrillation
Clint Koenig, MD, MS
Fulton, Missouri
AFFIRMed at last, it’s rate-controlling and not rhythm-controlling drugs that get the evidence-based nod for most types of atrial fibrillation. While rate and rhythm control were equally efficacious in most patient-oriented outcomes, the antiarrhythmics sent more people to the hospital and, potentially, killed more people than the rate controlling medications. The antiarrhythmics, especially amiodarone,9 do have a place in maintaining sinus rhythm in select patients with atrial fibrillation; but that role is limited and may be best managed with the help and support of a cardiologist.
The atrial fibrillation evidence also suggests that we need to place beta-blocker and non-dihydropyridine calcium-channel blockers (ie, verapamil and diltiazem) as first-line choices for rate-control therapy. Digoxin still has a place in our medical armamentarium; but its role is as an adjunct or backup to the blockers for most patients.
1. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-1833.
2. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet 2000;356:1789-1794.
3. Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834-1840.
4. Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study. J Am Coll Cardiol 2003;41:1690-1696.
5. Opolski G, Torbicki A, Kosior D, et al. Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFÉ Polish study. Kardiol Pol 2003;59:1-16.
6. McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003;139:1018-1033.
7. Segal JB, McNamara RL, Miller MR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Prac 2000;49:47-59.
8. Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2003;139:1009-1017.
9. AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003;42:20-29.
Rate control with long-term anticoagulation is recommended for most patients with atrial fibrillation (strength of recommendation [SOR]: A, based on randomized controlled trials [RCTs]). A rhythmcontrol strategy provides no survival or quality-of-life benefit when compared with rate control and causes more adverse drug effects and increased hospitalizations (SOR: A, based on RCTs).
Non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) and most beta-blockers are effective for controlling heart rate both at rest and during exercise (SOR: A, based on RCTs). Digoxin is only effective for rate control at rest and should be reserved for patients with systolic dysfunction or as an adjunct for those inadequately rate-controlled on calcium-channel blockers or beta-blockers (SOR: B, based on RCTs).
Subgroups in whom rhythm control may be superior are patients with persistent fatigue and dyspnea despite ventricular rate control and those unable to achieve adequate rate control. Both pharmacologic conversion (SOR: B, based on RCTs) and direct-current cardioversion (SOR: B, based on observational studies) are appropriate options in these patients.
Long-term anticoagulation is necessary for high-risk patients even if they are successfully managed with rhythm control (SOR: A, based on RCTs).
Evidence summary
Five recent RCTs have demonstrated similar mortality and cardiovascular morbidity in atrial fibrillation patients treated with either a rate-control or rhythm-control strategy.1-5
The AFFIRM trial, the largest (n=4060), was a nonblinded, randomized, multicenter study with an average follow-up of 3.5 years.1 The patients were aged 65 years or older and had at least 1 other risk factor for stroke. The rhythm-control group was given an antiarrhythmic medication chosen by the treating physician, while the rate-control group was given either a beta-blocker, a calcium-channel blocker, digoxin, or a combination of these as needed. Heart-rate goals were a resting pulse under 80 beats per minute, and a pulse after a 6-minute walk under 110 beats per minute. An intention-totreat analysis was followed.
There was no difference between the 2 groups for the composite endpoints of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest. A nonsignificant trend was observed for mortality favoring the rate-control group (relative risk [RR]=1.15; 95% confidence interval [CI], 0.99–1.34). Quality-of-life measures were equivalent in the 2 groups at all points in the study.1
More patients in the rhythm-control group required hospitalization (number needed to harm [NNH]=12.3; P<.001) and had adverse drug effects (P.001 for each of pulmonary events [NNH=18], gastrointestinal events [NNH=17], bradycardia [NNH=56], and prolonged QT [NNH=63]). This trial did not include younger patients without stroke risk factors, or those with paroxysmal atrial fibrillation.1
The 4 other RCTs also found no greater benefit with a rhythm-control strategy vs rate-control for most patients with atrial fibrillation.2-5
Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation.6,7 The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo.6,7
All beta-blockers tested were effective in rate-control during exercise and most (excluding labetalol and celiprolol) were effective at rest.6,7 Digoxin was ineffective during exercise and less effective than beta-blockers or calcium-channel blockers at rest.6-8 The combination of digoxin plus a calcium-channel blocker or beta-blocker may have increased benefit compared with either drug alone.6 Evidence was insufficient to recommend propafenone, clonidine, or amiodarone for rate control.7
In select patients, a rhythm-control approach may be desirable. A meta-analysis of 60 RCTs evaluated 8 drugs for acute cardioversion. Ibutilide, flecainide, dofetilide, propafenone, and amiodarone were found to have the strongest evidence of efficacy.6 There was moderate evidence for quinidine and insufficient evidence for disopyramide and sotalol.6 Studies of pharmacologic conversion suffer from small ample size, short follow-up, and variable duration of atrial fibrillation.6 A review of limited research reveals an 80% to 85% immediate success rate for DC cardioversion, with rare side-effects of ventricular tachycardia, transient AV node dysfunction, and significant skin blistering.6
For patients who elect a rhythm-control approach, RCTs demonstrate the need for continued long-term anticoagulation in high-risk patients even if they are maintained in sinus rhythm.1,4,5 (High-risk patients are defined as those aged >65 years, or those <65 years with 1 or more stroke risk factors: diabetes, hypertension, heart failure, prior transient ischemic attack or stroke or systemic embolism, or echocardiographic evidence of a left atrium >50 mm, a shortening fraction <25%, or an ejection fraction <40%.)
Recommendation from others
The American Academy of Family Practice/American College of Physicians’ clinical guidelines support a rate-control strategy for most patients with atrial fibrillation and recommend atenolol, metoprolol, diltiazem, or verapamil as the first-choice drugs.8 Digoxin is recommended as a second-line agent. DC cardioversion and pharmacologic conversion for patients who desire a rhythm-control strategy are described as “appropriate options.”8
Rate control best for atrial fibrillation
Clint Koenig, MD, MS
Fulton, Missouri
AFFIRMed at last, it’s rate-controlling and not rhythm-controlling drugs that get the evidence-based nod for most types of atrial fibrillation. While rate and rhythm control were equally efficacious in most patient-oriented outcomes, the antiarrhythmics sent more people to the hospital and, potentially, killed more people than the rate controlling medications. The antiarrhythmics, especially amiodarone,9 do have a place in maintaining sinus rhythm in select patients with atrial fibrillation; but that role is limited and may be best managed with the help and support of a cardiologist.
The atrial fibrillation evidence also suggests that we need to place beta-blocker and non-dihydropyridine calcium-channel blockers (ie, verapamil and diltiazem) as first-line choices for rate-control therapy. Digoxin still has a place in our medical armamentarium; but its role is as an adjunct or backup to the blockers for most patients.
Rate control with long-term anticoagulation is recommended for most patients with atrial fibrillation (strength of recommendation [SOR]: A, based on randomized controlled trials [RCTs]). A rhythmcontrol strategy provides no survival or quality-of-life benefit when compared with rate control and causes more adverse drug effects and increased hospitalizations (SOR: A, based on RCTs).
Non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) and most beta-blockers are effective for controlling heart rate both at rest and during exercise (SOR: A, based on RCTs). Digoxin is only effective for rate control at rest and should be reserved for patients with systolic dysfunction or as an adjunct for those inadequately rate-controlled on calcium-channel blockers or beta-blockers (SOR: B, based on RCTs).
Subgroups in whom rhythm control may be superior are patients with persistent fatigue and dyspnea despite ventricular rate control and those unable to achieve adequate rate control. Both pharmacologic conversion (SOR: B, based on RCTs) and direct-current cardioversion (SOR: B, based on observational studies) are appropriate options in these patients.
Long-term anticoagulation is necessary for high-risk patients even if they are successfully managed with rhythm control (SOR: A, based on RCTs).
Evidence summary
Five recent RCTs have demonstrated similar mortality and cardiovascular morbidity in atrial fibrillation patients treated with either a rate-control or rhythm-control strategy.1-5
The AFFIRM trial, the largest (n=4060), was a nonblinded, randomized, multicenter study with an average follow-up of 3.5 years.1 The patients were aged 65 years or older and had at least 1 other risk factor for stroke. The rhythm-control group was given an antiarrhythmic medication chosen by the treating physician, while the rate-control group was given either a beta-blocker, a calcium-channel blocker, digoxin, or a combination of these as needed. Heart-rate goals were a resting pulse under 80 beats per minute, and a pulse after a 6-minute walk under 110 beats per minute. An intention-totreat analysis was followed.
There was no difference between the 2 groups for the composite endpoints of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest. A nonsignificant trend was observed for mortality favoring the rate-control group (relative risk [RR]=1.15; 95% confidence interval [CI], 0.99–1.34). Quality-of-life measures were equivalent in the 2 groups at all points in the study.1
More patients in the rhythm-control group required hospitalization (number needed to harm [NNH]=12.3; P<.001) and had adverse drug effects (P.001 for each of pulmonary events [NNH=18], gastrointestinal events [NNH=17], bradycardia [NNH=56], and prolonged QT [NNH=63]). This trial did not include younger patients without stroke risk factors, or those with paroxysmal atrial fibrillation.1
The 4 other RCTs also found no greater benefit with a rhythm-control strategy vs rate-control for most patients with atrial fibrillation.2-5
Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation.6,7 The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo.6,7
All beta-blockers tested were effective in rate-control during exercise and most (excluding labetalol and celiprolol) were effective at rest.6,7 Digoxin was ineffective during exercise and less effective than beta-blockers or calcium-channel blockers at rest.6-8 The combination of digoxin plus a calcium-channel blocker or beta-blocker may have increased benefit compared with either drug alone.6 Evidence was insufficient to recommend propafenone, clonidine, or amiodarone for rate control.7
In select patients, a rhythm-control approach may be desirable. A meta-analysis of 60 RCTs evaluated 8 drugs for acute cardioversion. Ibutilide, flecainide, dofetilide, propafenone, and amiodarone were found to have the strongest evidence of efficacy.6 There was moderate evidence for quinidine and insufficient evidence for disopyramide and sotalol.6 Studies of pharmacologic conversion suffer from small ample size, short follow-up, and variable duration of atrial fibrillation.6 A review of limited research reveals an 80% to 85% immediate success rate for DC cardioversion, with rare side-effects of ventricular tachycardia, transient AV node dysfunction, and significant skin blistering.6
For patients who elect a rhythm-control approach, RCTs demonstrate the need for continued long-term anticoagulation in high-risk patients even if they are maintained in sinus rhythm.1,4,5 (High-risk patients are defined as those aged >65 years, or those <65 years with 1 or more stroke risk factors: diabetes, hypertension, heart failure, prior transient ischemic attack or stroke or systemic embolism, or echocardiographic evidence of a left atrium >50 mm, a shortening fraction <25%, or an ejection fraction <40%.)
Recommendation from others
The American Academy of Family Practice/American College of Physicians’ clinical guidelines support a rate-control strategy for most patients with atrial fibrillation and recommend atenolol, metoprolol, diltiazem, or verapamil as the first-choice drugs.8 Digoxin is recommended as a second-line agent. DC cardioversion and pharmacologic conversion for patients who desire a rhythm-control strategy are described as “appropriate options.”8
Rate control best for atrial fibrillation
Clint Koenig, MD, MS
Fulton, Missouri
AFFIRMed at last, it’s rate-controlling and not rhythm-controlling drugs that get the evidence-based nod for most types of atrial fibrillation. While rate and rhythm control were equally efficacious in most patient-oriented outcomes, the antiarrhythmics sent more people to the hospital and, potentially, killed more people than the rate controlling medications. The antiarrhythmics, especially amiodarone,9 do have a place in maintaining sinus rhythm in select patients with atrial fibrillation; but that role is limited and may be best managed with the help and support of a cardiologist.
The atrial fibrillation evidence also suggests that we need to place beta-blocker and non-dihydropyridine calcium-channel blockers (ie, verapamil and diltiazem) as first-line choices for rate-control therapy. Digoxin still has a place in our medical armamentarium; but its role is as an adjunct or backup to the blockers for most patients.
1. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-1833.
2. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet 2000;356:1789-1794.
3. Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834-1840.
4. Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study. J Am Coll Cardiol 2003;41:1690-1696.
5. Opolski G, Torbicki A, Kosior D, et al. Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFÉ Polish study. Kardiol Pol 2003;59:1-16.
6. McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003;139:1018-1033.
7. Segal JB, McNamara RL, Miller MR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Prac 2000;49:47-59.
8. Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2003;139:1009-1017.
9. AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003;42:20-29.
1. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-1833.
2. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet 2000;356:1789-1794.
3. Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834-1840.
4. Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study. J Am Coll Cardiol 2003;41:1690-1696.
5. Opolski G, Torbicki A, Kosior D, et al. Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFÉ Polish study. Kardiol Pol 2003;59:1-16.
6. McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003;139:1018-1033.
7. Segal JB, McNamara RL, Miller MR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Prac 2000;49:47-59.
8. Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2003;139:1009-1017.
9. AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003;42:20-29.
Evidence-based answers from the Family Physicians Inquiries Network