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Which patients undergoing noncardiac surgery benefit from perioperative beta-blockers?
Patients with moderate to high cardiac risk (a Revised Cardiac Risk Index [RCRI] score of 2 or higher [TABLE]) have a reduced risk of in-hospital death following perioperative beta-blocker therapy (strength of recommendation [SOR]: B, based on a large retrospective cohort study). There is, however, no proven benefit to perioperative beta-blocker therapy without prior cardiac risk stratification (SOR: A, based on systematic reviews).
Perioperative beta-blockers reduce cardiovascular risk even more when a long-acting beta-blocker (atenolol) is chosen over a shorter-acting one (metoprolol) (SOR: B, based on a retrospective cohort study), and when this therapy is titrated to a target heart rate of <65 BPM (SOR: B, based on cohort studies).
Perioperative beta-blocker therapy is most effective when initiated at least 30 days before surgery and continued throughout the hospital stay (SOR: C, expert opinion extrapolated from systematic review). Patients already on beta-blockers before surgery should continue at least through the perioperative period (SOR: C, expert opinion).
Who better than you to reduce your patient’s risk?
Vincent Lo, MD
San Joaquin Family Residency, French Camp, Calif
Family physicians are in an excellent position to assess and reduce their patients’ risks of complications from elective surgery.
While perioperative beta-blockers do not benefit every surgical patient, they do benefit certain high-risk patients. In fact, these same high-risk patients are often candidates for chronic beta-blocker therapy, according to current ACC/AHA guidelines. Thus, an upcoming surgery gives us another opportunity to identify these patients and get them treated.
Evidence summary
Studies without risk stratification find little benefit from beta-blockers
A systematic review including 25 randomized controlled trials (RCTs) evaluated perioperative beta-blocker therapy for noncardiac surgery in a total of 2722 patients who were not stratified according to cardiac risk status.1
Perioperative beta-blockers produced no significant effect on:
- all-cause mortality (odds ratio [OR]=0.78; 95% confidence interval [CI], 0.33–1.87),
- acute myocardial infarction (OR=0.59; 95% CI, 0.25–1.39),
- atrial fibrillation/flutter and other supraventricular arrhythmias (OR=0.43; 95% CI, 0.14–1.37), or
- length of hospital stay (weighted mean difference, –5.6 days; 95% CI, –12.2, 1.04).
However, in this review perioperative beta-blocker therapy reduced perioperative myocardial ischemia (OR=0.38; 95% CI, 0.21–0.69), and increased 2 adverse outcomes: hemodynamically significant bradycardia (OR=1.98; 95% CI, 1.08– 3.66) and hypotension requiring treatment (OR=2.52; 95% CI, 1.94–3.28).1 This study was limited by the inconsistent definition and assessment of outcomes among the individual trials.
No effect on total mortality, but a benefit in a composite outcome. An earlier systematic review with 22 RCTs and 2437 total patients, that was also not stratified according to cardiac risk status, found no effect from perioperative beta-blockers on total mortality or cardiovascular mortality alone. However, it did demonstrate a composite outcome of reduced cardiovascular mortality, reduced nonfatal myocardial infarction, and reduced nonfatal cardiac arrest (relative risk [RR]=0.44; 95% CI, 0.20–0.97) 30 days after surgery.2
Beta-blockers benefit certain high-risk patients
A retrospective cohort study evaluated the effect of perioperative beta-blocker therapy on perioperative mortality, according to preoperative RCRI assessment.3 The study population included 663,635 adults (mean age, 62 years) undergoing major noncardiac surgery at 329 US hospitals. Researchers calculated individual RCRI scores (TABLE).4 Half the patients had an RCRI of 0, 38% had an RCRI of 1, 10% had an RCRI of 2, and only 2% had an RCRI of 3 or greater.
Be wary of beta-blockers in low-risk patients. In the 580,665 patients with low cardiac risk, perioperative beta-blocker therapy increased the risk of in-hospital death: for all patients with an RCRI of 0: OR=1.36 (95% CI, 1.27–1.45); number needed to harm (NNH)=208; for all patients with an RCRI of 1: OR=1.09 (95% CI, 1.01–1.19); NNH=504).
A different story for high-risk cardiac patients. Perioperative beta-blocker therapy reduced the risk of in-hospital death in patients with an RCRI of 2 (OR=0.88; 95% CI, 0.80–0.98; number needed to treat [NNT]=227), an RCRI of 3 (OR=0.71; 95% CI, 0.63–0.80; NNT=62), or an RCRI of 4 or more (OR=0.58; 95% CI, 0.50–0.67; NNT=33).
TABLE
Before surgery, calculate your patient’s cardiac risk
| Assign 1 point for each of the following, and total: | ||
| ||
| POINTS | CLASS | RISK OF MAJOR CARDIAC EVENT* |
| 0 | I | 0.4% |
| 1 | II | 0.9% |
| 2 | III | 6.6% |
| 3+ | IV | 11% |
| *Major cardiac event includes myocardial infarction, pulmonary edema, ventricular fibrillation, primary cardiac arrest, and complete heart block. | ||
| Source: Lee et al, 1999.4 | ||
Long-acting beta-blockers=fewer MIs
A population-based, retrospective cohort analysis with 37,151 patients over 65 years of age compared perioperative beta-blocker therapy using atenolol (a long-acting beta-blocker) with metoprolol (a shorter-acting beta-blocker) for elective surgery.5 Investigators excluded patients with symptomatic coronary disease.
Patients taking atenolol had fewer MIs (1.6% vs 2.0%, P=.004) and fewer deaths (1.2% vs 1.6%, P=.007) when compared with metoprolol. Atenolol produced a 13% relative risk reduction over metoprolol for MI or death after adjusting for age, sex, type of surgery, and use of furosemide, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and statins (comparative NNT=165).
Dose titration by heart rate
An observational cohort study with 272 patients undergoing elective major vascular surgery (mean age 67.4 years, 80% male) evaluated whether higher doses of beta-blockers and tight heart rate control reduced perioperative myocardial ischemia and troponin T release.6 Patients with higher beta-blocker doses, lower heart rates, and lower absolute change in heart rate during the perioperative period had significantly less perioperative myocardial ischemia and troponin T release (P<.0001).
The DECREASE-II trial, a prospective cohort study with 1476 patients undergoing elective open abdominal aortic or infrainguinal arterial reconstruction also found that patients with heart rates <65 beats per minute had a significantly lower risk of cardiac death or MI at 30 days postoperatively (1.3% vs 5.2%, OR=0.24; 95% CI, 0.09–0.66).7
Begin therapy 30 days before surgery
Authors of a systematic review including 5 RCTs (586 total patients) evaluating perioperative beta-blocker therapy in noncardiac surgery concluded that beta-blocker therapy should begin as long as 30 days prior to surgery to allow for titration of dose to the target heart rate and continue at least throughout hospitalization (longer if adequate medical follow-up can be arranged postoperatively).8
Recommendations from others
The American College of Cardiology/American Heart Association Task Force on Practice Guidelines9 recommends:
- continuing beta-blockers for patients already receiving them to treat angina, symptomatic arrhythmias, and hypertension before their surgical risk evaluation.
- initiating perioperative beta-blocker therapy for patients undergoing vascular surgery if they are at high cardiac risk, as evidenced by ischemia on preoperative testing.
- considering perioperative beta-blocker therapy for patients undergoing intermediate-to high-risk procedures if preoperative risk assessment identifies them as having intermediate or higher cardiac risk, and for patients undergoing vascular surgery who are at low cardiac risk.
1. Wiesbauer F, Schlager O, Domanovits H, et al. Perioperative beta-blockers for preventing surgery-related mortality and morbidity: A systematic review and meta-analysis. Anesth Analg 2007;104:27-41.
2. Devereaux PJ, Beattie WS, Choi PT, et al. How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 2005;331:313-321.
3. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM, et al. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 2005;353:349-361.
4. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-1049.
5. Redelmeier D, Scales D, Kopp A. Beta blockers for elective surgery in elderly patients: population based, retrospective cohort study. BMJ 2005;331:932.-Epub 2005 Oct 6.
6. Feringa HH, Bax JJ, Boersma E, et al. High-dose beta-blockers and tight heart rate control reduce myocardial ischemia and troponin T release in vascular surgery patients. Circulation 2006;114:I344-I349.
7. Poldermans D, Bax JJ, Schouten O, et al. Should major vascular surgery be delayed because of preoperative cardiac testing in intermediate-risk patients receiving beta-blocker therapy with tight heart rate control? J Am Coll Cardiol 2006;48:964-969.
8. Auerbach AD, Goldman L. Beta-blockers and reduction of cardiac events in noncardiac surgery: scientific review. JAMA 2002;287:1435-1444.
9. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2006;113:2662-2674.
Patients with moderate to high cardiac risk (a Revised Cardiac Risk Index [RCRI] score of 2 or higher [TABLE]) have a reduced risk of in-hospital death following perioperative beta-blocker therapy (strength of recommendation [SOR]: B, based on a large retrospective cohort study). There is, however, no proven benefit to perioperative beta-blocker therapy without prior cardiac risk stratification (SOR: A, based on systematic reviews).
Perioperative beta-blockers reduce cardiovascular risk even more when a long-acting beta-blocker (atenolol) is chosen over a shorter-acting one (metoprolol) (SOR: B, based on a retrospective cohort study), and when this therapy is titrated to a target heart rate of <65 BPM (SOR: B, based on cohort studies).
Perioperative beta-blocker therapy is most effective when initiated at least 30 days before surgery and continued throughout the hospital stay (SOR: C, expert opinion extrapolated from systematic review). Patients already on beta-blockers before surgery should continue at least through the perioperative period (SOR: C, expert opinion).
Who better than you to reduce your patient’s risk?
Vincent Lo, MD
San Joaquin Family Residency, French Camp, Calif
Family physicians are in an excellent position to assess and reduce their patients’ risks of complications from elective surgery.
While perioperative beta-blockers do not benefit every surgical patient, they do benefit certain high-risk patients. In fact, these same high-risk patients are often candidates for chronic beta-blocker therapy, according to current ACC/AHA guidelines. Thus, an upcoming surgery gives us another opportunity to identify these patients and get them treated.
Evidence summary
Studies without risk stratification find little benefit from beta-blockers
A systematic review including 25 randomized controlled trials (RCTs) evaluated perioperative beta-blocker therapy for noncardiac surgery in a total of 2722 patients who were not stratified according to cardiac risk status.1
Perioperative beta-blockers produced no significant effect on:
- all-cause mortality (odds ratio [OR]=0.78; 95% confidence interval [CI], 0.33–1.87),
- acute myocardial infarction (OR=0.59; 95% CI, 0.25–1.39),
- atrial fibrillation/flutter and other supraventricular arrhythmias (OR=0.43; 95% CI, 0.14–1.37), or
- length of hospital stay (weighted mean difference, –5.6 days; 95% CI, –12.2, 1.04).
However, in this review perioperative beta-blocker therapy reduced perioperative myocardial ischemia (OR=0.38; 95% CI, 0.21–0.69), and increased 2 adverse outcomes: hemodynamically significant bradycardia (OR=1.98; 95% CI, 1.08– 3.66) and hypotension requiring treatment (OR=2.52; 95% CI, 1.94–3.28).1 This study was limited by the inconsistent definition and assessment of outcomes among the individual trials.
No effect on total mortality, but a benefit in a composite outcome. An earlier systematic review with 22 RCTs and 2437 total patients, that was also not stratified according to cardiac risk status, found no effect from perioperative beta-blockers on total mortality or cardiovascular mortality alone. However, it did demonstrate a composite outcome of reduced cardiovascular mortality, reduced nonfatal myocardial infarction, and reduced nonfatal cardiac arrest (relative risk [RR]=0.44; 95% CI, 0.20–0.97) 30 days after surgery.2
Beta-blockers benefit certain high-risk patients
A retrospective cohort study evaluated the effect of perioperative beta-blocker therapy on perioperative mortality, according to preoperative RCRI assessment.3 The study population included 663,635 adults (mean age, 62 years) undergoing major noncardiac surgery at 329 US hospitals. Researchers calculated individual RCRI scores (TABLE).4 Half the patients had an RCRI of 0, 38% had an RCRI of 1, 10% had an RCRI of 2, and only 2% had an RCRI of 3 or greater.
Be wary of beta-blockers in low-risk patients. In the 580,665 patients with low cardiac risk, perioperative beta-blocker therapy increased the risk of in-hospital death: for all patients with an RCRI of 0: OR=1.36 (95% CI, 1.27–1.45); number needed to harm (NNH)=208; for all patients with an RCRI of 1: OR=1.09 (95% CI, 1.01–1.19); NNH=504).
A different story for high-risk cardiac patients. Perioperative beta-blocker therapy reduced the risk of in-hospital death in patients with an RCRI of 2 (OR=0.88; 95% CI, 0.80–0.98; number needed to treat [NNT]=227), an RCRI of 3 (OR=0.71; 95% CI, 0.63–0.80; NNT=62), or an RCRI of 4 or more (OR=0.58; 95% CI, 0.50–0.67; NNT=33).
TABLE
Before surgery, calculate your patient’s cardiac risk
| Assign 1 point for each of the following, and total: | ||
| ||
| POINTS | CLASS | RISK OF MAJOR CARDIAC EVENT* |
| 0 | I | 0.4% |
| 1 | II | 0.9% |
| 2 | III | 6.6% |
| 3+ | IV | 11% |
| *Major cardiac event includes myocardial infarction, pulmonary edema, ventricular fibrillation, primary cardiac arrest, and complete heart block. | ||
| Source: Lee et al, 1999.4 | ||
Long-acting beta-blockers=fewer MIs
A population-based, retrospective cohort analysis with 37,151 patients over 65 years of age compared perioperative beta-blocker therapy using atenolol (a long-acting beta-blocker) with metoprolol (a shorter-acting beta-blocker) for elective surgery.5 Investigators excluded patients with symptomatic coronary disease.
Patients taking atenolol had fewer MIs (1.6% vs 2.0%, P=.004) and fewer deaths (1.2% vs 1.6%, P=.007) when compared with metoprolol. Atenolol produced a 13% relative risk reduction over metoprolol for MI or death after adjusting for age, sex, type of surgery, and use of furosemide, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and statins (comparative NNT=165).
Dose titration by heart rate
An observational cohort study with 272 patients undergoing elective major vascular surgery (mean age 67.4 years, 80% male) evaluated whether higher doses of beta-blockers and tight heart rate control reduced perioperative myocardial ischemia and troponin T release.6 Patients with higher beta-blocker doses, lower heart rates, and lower absolute change in heart rate during the perioperative period had significantly less perioperative myocardial ischemia and troponin T release (P<.0001).
The DECREASE-II trial, a prospective cohort study with 1476 patients undergoing elective open abdominal aortic or infrainguinal arterial reconstruction also found that patients with heart rates <65 beats per minute had a significantly lower risk of cardiac death or MI at 30 days postoperatively (1.3% vs 5.2%, OR=0.24; 95% CI, 0.09–0.66).7
Begin therapy 30 days before surgery
Authors of a systematic review including 5 RCTs (586 total patients) evaluating perioperative beta-blocker therapy in noncardiac surgery concluded that beta-blocker therapy should begin as long as 30 days prior to surgery to allow for titration of dose to the target heart rate and continue at least throughout hospitalization (longer if adequate medical follow-up can be arranged postoperatively).8
Recommendations from others
The American College of Cardiology/American Heart Association Task Force on Practice Guidelines9 recommends:
- continuing beta-blockers for patients already receiving them to treat angina, symptomatic arrhythmias, and hypertension before their surgical risk evaluation.
- initiating perioperative beta-blocker therapy for patients undergoing vascular surgery if they are at high cardiac risk, as evidenced by ischemia on preoperative testing.
- considering perioperative beta-blocker therapy for patients undergoing intermediate-to high-risk procedures if preoperative risk assessment identifies them as having intermediate or higher cardiac risk, and for patients undergoing vascular surgery who are at low cardiac risk.
Patients with moderate to high cardiac risk (a Revised Cardiac Risk Index [RCRI] score of 2 or higher [TABLE]) have a reduced risk of in-hospital death following perioperative beta-blocker therapy (strength of recommendation [SOR]: B, based on a large retrospective cohort study). There is, however, no proven benefit to perioperative beta-blocker therapy without prior cardiac risk stratification (SOR: A, based on systematic reviews).
Perioperative beta-blockers reduce cardiovascular risk even more when a long-acting beta-blocker (atenolol) is chosen over a shorter-acting one (metoprolol) (SOR: B, based on a retrospective cohort study), and when this therapy is titrated to a target heart rate of <65 BPM (SOR: B, based on cohort studies).
Perioperative beta-blocker therapy is most effective when initiated at least 30 days before surgery and continued throughout the hospital stay (SOR: C, expert opinion extrapolated from systematic review). Patients already on beta-blockers before surgery should continue at least through the perioperative period (SOR: C, expert opinion).
Who better than you to reduce your patient’s risk?
Vincent Lo, MD
San Joaquin Family Residency, French Camp, Calif
Family physicians are in an excellent position to assess and reduce their patients’ risks of complications from elective surgery.
While perioperative beta-blockers do not benefit every surgical patient, they do benefit certain high-risk patients. In fact, these same high-risk patients are often candidates for chronic beta-blocker therapy, according to current ACC/AHA guidelines. Thus, an upcoming surgery gives us another opportunity to identify these patients and get them treated.
Evidence summary
Studies without risk stratification find little benefit from beta-blockers
A systematic review including 25 randomized controlled trials (RCTs) evaluated perioperative beta-blocker therapy for noncardiac surgery in a total of 2722 patients who were not stratified according to cardiac risk status.1
Perioperative beta-blockers produced no significant effect on:
- all-cause mortality (odds ratio [OR]=0.78; 95% confidence interval [CI], 0.33–1.87),
- acute myocardial infarction (OR=0.59; 95% CI, 0.25–1.39),
- atrial fibrillation/flutter and other supraventricular arrhythmias (OR=0.43; 95% CI, 0.14–1.37), or
- length of hospital stay (weighted mean difference, –5.6 days; 95% CI, –12.2, 1.04).
However, in this review perioperative beta-blocker therapy reduced perioperative myocardial ischemia (OR=0.38; 95% CI, 0.21–0.69), and increased 2 adverse outcomes: hemodynamically significant bradycardia (OR=1.98; 95% CI, 1.08– 3.66) and hypotension requiring treatment (OR=2.52; 95% CI, 1.94–3.28).1 This study was limited by the inconsistent definition and assessment of outcomes among the individual trials.
No effect on total mortality, but a benefit in a composite outcome. An earlier systematic review with 22 RCTs and 2437 total patients, that was also not stratified according to cardiac risk status, found no effect from perioperative beta-blockers on total mortality or cardiovascular mortality alone. However, it did demonstrate a composite outcome of reduced cardiovascular mortality, reduced nonfatal myocardial infarction, and reduced nonfatal cardiac arrest (relative risk [RR]=0.44; 95% CI, 0.20–0.97) 30 days after surgery.2
Beta-blockers benefit certain high-risk patients
A retrospective cohort study evaluated the effect of perioperative beta-blocker therapy on perioperative mortality, according to preoperative RCRI assessment.3 The study population included 663,635 adults (mean age, 62 years) undergoing major noncardiac surgery at 329 US hospitals. Researchers calculated individual RCRI scores (TABLE).4 Half the patients had an RCRI of 0, 38% had an RCRI of 1, 10% had an RCRI of 2, and only 2% had an RCRI of 3 or greater.
Be wary of beta-blockers in low-risk patients. In the 580,665 patients with low cardiac risk, perioperative beta-blocker therapy increased the risk of in-hospital death: for all patients with an RCRI of 0: OR=1.36 (95% CI, 1.27–1.45); number needed to harm (NNH)=208; for all patients with an RCRI of 1: OR=1.09 (95% CI, 1.01–1.19); NNH=504).
A different story for high-risk cardiac patients. Perioperative beta-blocker therapy reduced the risk of in-hospital death in patients with an RCRI of 2 (OR=0.88; 95% CI, 0.80–0.98; number needed to treat [NNT]=227), an RCRI of 3 (OR=0.71; 95% CI, 0.63–0.80; NNT=62), or an RCRI of 4 or more (OR=0.58; 95% CI, 0.50–0.67; NNT=33).
TABLE
Before surgery, calculate your patient’s cardiac risk
| Assign 1 point for each of the following, and total: | ||
| ||
| POINTS | CLASS | RISK OF MAJOR CARDIAC EVENT* |
| 0 | I | 0.4% |
| 1 | II | 0.9% |
| 2 | III | 6.6% |
| 3+ | IV | 11% |
| *Major cardiac event includes myocardial infarction, pulmonary edema, ventricular fibrillation, primary cardiac arrest, and complete heart block. | ||
| Source: Lee et al, 1999.4 | ||
Long-acting beta-blockers=fewer MIs
A population-based, retrospective cohort analysis with 37,151 patients over 65 years of age compared perioperative beta-blocker therapy using atenolol (a long-acting beta-blocker) with metoprolol (a shorter-acting beta-blocker) for elective surgery.5 Investigators excluded patients with symptomatic coronary disease.
Patients taking atenolol had fewer MIs (1.6% vs 2.0%, P=.004) and fewer deaths (1.2% vs 1.6%, P=.007) when compared with metoprolol. Atenolol produced a 13% relative risk reduction over metoprolol for MI or death after adjusting for age, sex, type of surgery, and use of furosemide, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and statins (comparative NNT=165).
Dose titration by heart rate
An observational cohort study with 272 patients undergoing elective major vascular surgery (mean age 67.4 years, 80% male) evaluated whether higher doses of beta-blockers and tight heart rate control reduced perioperative myocardial ischemia and troponin T release.6 Patients with higher beta-blocker doses, lower heart rates, and lower absolute change in heart rate during the perioperative period had significantly less perioperative myocardial ischemia and troponin T release (P<.0001).
The DECREASE-II trial, a prospective cohort study with 1476 patients undergoing elective open abdominal aortic or infrainguinal arterial reconstruction also found that patients with heart rates <65 beats per minute had a significantly lower risk of cardiac death or MI at 30 days postoperatively (1.3% vs 5.2%, OR=0.24; 95% CI, 0.09–0.66).7
Begin therapy 30 days before surgery
Authors of a systematic review including 5 RCTs (586 total patients) evaluating perioperative beta-blocker therapy in noncardiac surgery concluded that beta-blocker therapy should begin as long as 30 days prior to surgery to allow for titration of dose to the target heart rate and continue at least throughout hospitalization (longer if adequate medical follow-up can be arranged postoperatively).8
Recommendations from others
The American College of Cardiology/American Heart Association Task Force on Practice Guidelines9 recommends:
- continuing beta-blockers for patients already receiving them to treat angina, symptomatic arrhythmias, and hypertension before their surgical risk evaluation.
- initiating perioperative beta-blocker therapy for patients undergoing vascular surgery if they are at high cardiac risk, as evidenced by ischemia on preoperative testing.
- considering perioperative beta-blocker therapy for patients undergoing intermediate-to high-risk procedures if preoperative risk assessment identifies them as having intermediate or higher cardiac risk, and for patients undergoing vascular surgery who are at low cardiac risk.
1. Wiesbauer F, Schlager O, Domanovits H, et al. Perioperative beta-blockers for preventing surgery-related mortality and morbidity: A systematic review and meta-analysis. Anesth Analg 2007;104:27-41.
2. Devereaux PJ, Beattie WS, Choi PT, et al. How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 2005;331:313-321.
3. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM, et al. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 2005;353:349-361.
4. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-1049.
5. Redelmeier D, Scales D, Kopp A. Beta blockers for elective surgery in elderly patients: population based, retrospective cohort study. BMJ 2005;331:932.-Epub 2005 Oct 6.
6. Feringa HH, Bax JJ, Boersma E, et al. High-dose beta-blockers and tight heart rate control reduce myocardial ischemia and troponin T release in vascular surgery patients. Circulation 2006;114:I344-I349.
7. Poldermans D, Bax JJ, Schouten O, et al. Should major vascular surgery be delayed because of preoperative cardiac testing in intermediate-risk patients receiving beta-blocker therapy with tight heart rate control? J Am Coll Cardiol 2006;48:964-969.
8. Auerbach AD, Goldman L. Beta-blockers and reduction of cardiac events in noncardiac surgery: scientific review. JAMA 2002;287:1435-1444.
9. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2006;113:2662-2674.
1. Wiesbauer F, Schlager O, Domanovits H, et al. Perioperative beta-blockers for preventing surgery-related mortality and morbidity: A systematic review and meta-analysis. Anesth Analg 2007;104:27-41.
2. Devereaux PJ, Beattie WS, Choi PT, et al. How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 2005;331:313-321.
3. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM, et al. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 2005;353:349-361.
4. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-1049.
5. Redelmeier D, Scales D, Kopp A. Beta blockers for elective surgery in elderly patients: population based, retrospective cohort study. BMJ 2005;331:932.-Epub 2005 Oct 6.
6. Feringa HH, Bax JJ, Boersma E, et al. High-dose beta-blockers and tight heart rate control reduce myocardial ischemia and troponin T release in vascular surgery patients. Circulation 2006;114:I344-I349.
7. Poldermans D, Bax JJ, Schouten O, et al. Should major vascular surgery be delayed because of preoperative cardiac testing in intermediate-risk patients receiving beta-blocker therapy with tight heart rate control? J Am Coll Cardiol 2006;48:964-969.
8. Auerbach AD, Goldman L. Beta-blockers and reduction of cardiac events in noncardiac surgery: scientific review. JAMA 2002;287:1435-1444.
9. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2006;113:2662-2674.
Evidence-based answers from the Family Physicians Inquiries Network
What is the interval for monitoring warfarin therapy once therapeutic levels are achieved?
The international normalized ratio (INR) should be measured monthly once therapeutic levels are achieved and are stable for at least 8 weeks, although treatment should be individualized and an increased frequency may be required by some patients (Table) (strength of recommendation [SOR]: C, consensus statements). For highly compliant patients with stable levels and a clear understanding of factors that influence anticoagulation (changes in health, diet, medications), routine monitoring may be extended to 6 weeks (SOR: B, single randomized controlled trial [RCT]) or longer (SOR: C, case series). Patient-managed warfarin therapy, using biweekly self-measurements, results in more time in therapeutic range than routine physicianmanaged care (SOR: A, RCTs).
TABLE
Approach to monitoring of INR for long-term anticoagulation
| Clinical scenario | Suggested approach |
|---|---|
| Initiation of warfarin | Monitor daily until stable, then gradually increase interval to weekly, biweekly, monthly if stable |
| INR reaches therapeutic level | Recheck 2 weeks x 2, then every 4 weeks if stable |
| INR therapeutic for 8 to 10 weeks consecutively | May increase interval to 6 weeks with high compliance and good patient education; increase frequency with illness, medication change, history of highly variable INR levels |
| INR outside target range within 1.0 points | Recheck in 1 to 2 weeks; if persists, adjust dose and recheck in 1–2 weeks |
| INR > from target range but less than 5 | Adjust dose, recheck in 1 week |
| INR between 5 and 8.9 | Hold warfarin 1 to 2 days, recheck 24 to 48 hours, adjust dose, consider oral vitamin K, but may lead to warfarin resistance |
| INR >9 | Hold warfarin, closely monitor. Bleeding risk increases with higher INR levels. Management may include admission, administration of oral or IV vitamin K, transfusion with fresh frozen plasma if INR very high or high risk of bleeding |
Evidence summary
Under- or over-treatment with warfarin can result in life-threatening complications. Limited research exists to guide the selection of an interval for monitoring anticoagulation in stabilized patients. One RCT compared INR monitoring in an anticoagulation clinic at 6 weeks and 4 weeks among 124 patients with a prosthetic heart valve on stable oral anticoagulant treatment and found no difference in thromboembolic or hemorrhagic events.1 A study in the United Kingdom used a 14-week interval for selected patients, but it used no comparison group.2 Kent et al developed a computer-based model to compute the optimum interval for monitoring anticoagulation that considers the variability of the patient’s previous levels and costs associated with testing and potential complications. This model achieved a maximum interval of 11 weeks for very stable patients.3
More frequent testing results in higher time in therapeutic range, particularly when patients selfmonitor. A German study of 200 patients with prosthetic heart valves found that they tested within a therapeutic range 48% of the time when monitored by their physician “as usual” (average interval 24 days), and 64% of the time when the interval was increased to 2 weeks.4 When the same patients then went to self-monitoring every 8, 4, and 2 days, they achieved therapeutic levels 76%, 89%, and 90% of the time, respectively. Bleeding and thromboembolic complications were not reported, but have been demonstrated elsewhere to be lower among patients who self-test frequently (eg, twice weekly) when compared with usual care (average interval 19 days) (4.49% and 0.9% vs 10.9% and 3.6%; number needed to treat [NNT]=15.6 for bleeding, NNT=37 for thromboembolism).5
Recommendations from others
The American College of Chest Physicians (ACCP) recommends individualizing management as the optimal frequency of INR monitoring varies according to patient compliance, dosing decisions, duration of therapy and changes in health, diet, or medications.6 The ACCP, the American Heart Association,7 Micromedex DrugPoints System,8 Goodman and Gilman’s Pharmacological Basis of Therapeutics.,9 and Cecil’s Textbook of Medicine.10 all recommend monthly monitoring once stable. The Institute for Clinical Systems Improvement’s Anticoagulation Therapy Supplement Management.11 and Managing Oral Anticoagulation Therapy Clinical and Operation al Guidelines.12 also recommend monthly monitoring for stable patients, but suggest that the interval can be increased to 6 weeks for selected stable patients.
Clear and consistent communication between physician and patient is essential
Rick Guthmann, MD
Advocate Illinois Masonic Medical Center
Once a month warfarin monitoring remains a sensible interval after the therapeutic level is achieved. Maintaining a standard routine simplifies the many instructions that physicians give and patients receive. This clear, consistent plan can improve coordination of care by medical staff and compliance by patients. Additionally, monitoring has secondary benefits; it reinforces the risks associated with warfarin, and it provides further opportunities to educate the patient.
1. Pengo V, Barbero F, Biasiolo A, Pegoraro C, Cucchini U, Iliceto S. A comparison between six- and four-week intervals in surveillance of oral anticoagulant treatment. Am J Clin Pathol 2003;120:944-947.
2. Lidstone V, Janes S, Stross P. INR: Intervals of measurement can safely extend to 14 weeks. Clin Lab Haematol 2000;22:291-293.
3. Kent DL, Vermes D, McDonell M, Henikoff J, Fihn SD. A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Warfarin Optimal Outpatient Follow-up Study Group. Med Decis Making 1992;12:132-141.
4. Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis 1998;5 Suppl 1:19-24.
5. Horstkotte D, Piper C, Wiemer M, Schulte HD, Schultheib HP. Improvement of prognosis by home prothrombin estimation in patients with life long anticoagulation therapy. Eur Heart J 1996;17(supp):230 (abstract 1326).-
6. Ansell J, Hirsh J, Dalen J, et al. Managing oral anticoagulant therapy. Chest 2001;119(1 Suppl):22S-38S.
7. Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 2: Oral anticoagulants. American Heart Association. Circulation 1994;89:1469-1480.Erratum in Circulation. 1995; 91:A55–A56.
8. MICROMEDEX Drug Points System. Available at: www.micromedex.com. Accessed on January 8, 2005.
9. Hardman JG, Limbird LE, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.
10. Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa: WB Saunders, 2004.
11. Institute for Clinical Systems Integration. Health Care Guidelines: Anticoagulation Therapy. Supplement Management. Bloomington, Minn: ICSI; 2003.
12. Oertel LB. Managing maintenance therapy. In: Ansell JE, et al, eds. Managing Oral Anticoagulation Therapy: Clinical and Operational Guidelines. Gaithersburg, Md: Aspen; 1998.
The international normalized ratio (INR) should be measured monthly once therapeutic levels are achieved and are stable for at least 8 weeks, although treatment should be individualized and an increased frequency may be required by some patients (Table) (strength of recommendation [SOR]: C, consensus statements). For highly compliant patients with stable levels and a clear understanding of factors that influence anticoagulation (changes in health, diet, medications), routine monitoring may be extended to 6 weeks (SOR: B, single randomized controlled trial [RCT]) or longer (SOR: C, case series). Patient-managed warfarin therapy, using biweekly self-measurements, results in more time in therapeutic range than routine physicianmanaged care (SOR: A, RCTs).
TABLE
Approach to monitoring of INR for long-term anticoagulation
| Clinical scenario | Suggested approach |
|---|---|
| Initiation of warfarin | Monitor daily until stable, then gradually increase interval to weekly, biweekly, monthly if stable |
| INR reaches therapeutic level | Recheck 2 weeks x 2, then every 4 weeks if stable |
| INR therapeutic for 8 to 10 weeks consecutively | May increase interval to 6 weeks with high compliance and good patient education; increase frequency with illness, medication change, history of highly variable INR levels |
| INR outside target range within 1.0 points | Recheck in 1 to 2 weeks; if persists, adjust dose and recheck in 1–2 weeks |
| INR > from target range but less than 5 | Adjust dose, recheck in 1 week |
| INR between 5 and 8.9 | Hold warfarin 1 to 2 days, recheck 24 to 48 hours, adjust dose, consider oral vitamin K, but may lead to warfarin resistance |
| INR >9 | Hold warfarin, closely monitor. Bleeding risk increases with higher INR levels. Management may include admission, administration of oral or IV vitamin K, transfusion with fresh frozen plasma if INR very high or high risk of bleeding |
Evidence summary
Under- or over-treatment with warfarin can result in life-threatening complications. Limited research exists to guide the selection of an interval for monitoring anticoagulation in stabilized patients. One RCT compared INR monitoring in an anticoagulation clinic at 6 weeks and 4 weeks among 124 patients with a prosthetic heart valve on stable oral anticoagulant treatment and found no difference in thromboembolic or hemorrhagic events.1 A study in the United Kingdom used a 14-week interval for selected patients, but it used no comparison group.2 Kent et al developed a computer-based model to compute the optimum interval for monitoring anticoagulation that considers the variability of the patient’s previous levels and costs associated with testing and potential complications. This model achieved a maximum interval of 11 weeks for very stable patients.3
More frequent testing results in higher time in therapeutic range, particularly when patients selfmonitor. A German study of 200 patients with prosthetic heart valves found that they tested within a therapeutic range 48% of the time when monitored by their physician “as usual” (average interval 24 days), and 64% of the time when the interval was increased to 2 weeks.4 When the same patients then went to self-monitoring every 8, 4, and 2 days, they achieved therapeutic levels 76%, 89%, and 90% of the time, respectively. Bleeding and thromboembolic complications were not reported, but have been demonstrated elsewhere to be lower among patients who self-test frequently (eg, twice weekly) when compared with usual care (average interval 19 days) (4.49% and 0.9% vs 10.9% and 3.6%; number needed to treat [NNT]=15.6 for bleeding, NNT=37 for thromboembolism).5
Recommendations from others
The American College of Chest Physicians (ACCP) recommends individualizing management as the optimal frequency of INR monitoring varies according to patient compliance, dosing decisions, duration of therapy and changes in health, diet, or medications.6 The ACCP, the American Heart Association,7 Micromedex DrugPoints System,8 Goodman and Gilman’s Pharmacological Basis of Therapeutics.,9 and Cecil’s Textbook of Medicine.10 all recommend monthly monitoring once stable. The Institute for Clinical Systems Improvement’s Anticoagulation Therapy Supplement Management.11 and Managing Oral Anticoagulation Therapy Clinical and Operation al Guidelines.12 also recommend monthly monitoring for stable patients, but suggest that the interval can be increased to 6 weeks for selected stable patients.
Clear and consistent communication between physician and patient is essential
Rick Guthmann, MD
Advocate Illinois Masonic Medical Center
Once a month warfarin monitoring remains a sensible interval after the therapeutic level is achieved. Maintaining a standard routine simplifies the many instructions that physicians give and patients receive. This clear, consistent plan can improve coordination of care by medical staff and compliance by patients. Additionally, monitoring has secondary benefits; it reinforces the risks associated with warfarin, and it provides further opportunities to educate the patient.
The international normalized ratio (INR) should be measured monthly once therapeutic levels are achieved and are stable for at least 8 weeks, although treatment should be individualized and an increased frequency may be required by some patients (Table) (strength of recommendation [SOR]: C, consensus statements). For highly compliant patients with stable levels and a clear understanding of factors that influence anticoagulation (changes in health, diet, medications), routine monitoring may be extended to 6 weeks (SOR: B, single randomized controlled trial [RCT]) or longer (SOR: C, case series). Patient-managed warfarin therapy, using biweekly self-measurements, results in more time in therapeutic range than routine physicianmanaged care (SOR: A, RCTs).
TABLE
Approach to monitoring of INR for long-term anticoagulation
| Clinical scenario | Suggested approach |
|---|---|
| Initiation of warfarin | Monitor daily until stable, then gradually increase interval to weekly, biweekly, monthly if stable |
| INR reaches therapeutic level | Recheck 2 weeks x 2, then every 4 weeks if stable |
| INR therapeutic for 8 to 10 weeks consecutively | May increase interval to 6 weeks with high compliance and good patient education; increase frequency with illness, medication change, history of highly variable INR levels |
| INR outside target range within 1.0 points | Recheck in 1 to 2 weeks; if persists, adjust dose and recheck in 1–2 weeks |
| INR > from target range but less than 5 | Adjust dose, recheck in 1 week |
| INR between 5 and 8.9 | Hold warfarin 1 to 2 days, recheck 24 to 48 hours, adjust dose, consider oral vitamin K, but may lead to warfarin resistance |
| INR >9 | Hold warfarin, closely monitor. Bleeding risk increases with higher INR levels. Management may include admission, administration of oral or IV vitamin K, transfusion with fresh frozen plasma if INR very high or high risk of bleeding |
Evidence summary
Under- or over-treatment with warfarin can result in life-threatening complications. Limited research exists to guide the selection of an interval for monitoring anticoagulation in stabilized patients. One RCT compared INR monitoring in an anticoagulation clinic at 6 weeks and 4 weeks among 124 patients with a prosthetic heart valve on stable oral anticoagulant treatment and found no difference in thromboembolic or hemorrhagic events.1 A study in the United Kingdom used a 14-week interval for selected patients, but it used no comparison group.2 Kent et al developed a computer-based model to compute the optimum interval for monitoring anticoagulation that considers the variability of the patient’s previous levels and costs associated with testing and potential complications. This model achieved a maximum interval of 11 weeks for very stable patients.3
More frequent testing results in higher time in therapeutic range, particularly when patients selfmonitor. A German study of 200 patients with prosthetic heart valves found that they tested within a therapeutic range 48% of the time when monitored by their physician “as usual” (average interval 24 days), and 64% of the time when the interval was increased to 2 weeks.4 When the same patients then went to self-monitoring every 8, 4, and 2 days, they achieved therapeutic levels 76%, 89%, and 90% of the time, respectively. Bleeding and thromboembolic complications were not reported, but have been demonstrated elsewhere to be lower among patients who self-test frequently (eg, twice weekly) when compared with usual care (average interval 19 days) (4.49% and 0.9% vs 10.9% and 3.6%; number needed to treat [NNT]=15.6 for bleeding, NNT=37 for thromboembolism).5
Recommendations from others
The American College of Chest Physicians (ACCP) recommends individualizing management as the optimal frequency of INR monitoring varies according to patient compliance, dosing decisions, duration of therapy and changes in health, diet, or medications.6 The ACCP, the American Heart Association,7 Micromedex DrugPoints System,8 Goodman and Gilman’s Pharmacological Basis of Therapeutics.,9 and Cecil’s Textbook of Medicine.10 all recommend monthly monitoring once stable. The Institute for Clinical Systems Improvement’s Anticoagulation Therapy Supplement Management.11 and Managing Oral Anticoagulation Therapy Clinical and Operation al Guidelines.12 also recommend monthly monitoring for stable patients, but suggest that the interval can be increased to 6 weeks for selected stable patients.
Clear and consistent communication between physician and patient is essential
Rick Guthmann, MD
Advocate Illinois Masonic Medical Center
Once a month warfarin monitoring remains a sensible interval after the therapeutic level is achieved. Maintaining a standard routine simplifies the many instructions that physicians give and patients receive. This clear, consistent plan can improve coordination of care by medical staff and compliance by patients. Additionally, monitoring has secondary benefits; it reinforces the risks associated with warfarin, and it provides further opportunities to educate the patient.
1. Pengo V, Barbero F, Biasiolo A, Pegoraro C, Cucchini U, Iliceto S. A comparison between six- and four-week intervals in surveillance of oral anticoagulant treatment. Am J Clin Pathol 2003;120:944-947.
2. Lidstone V, Janes S, Stross P. INR: Intervals of measurement can safely extend to 14 weeks. Clin Lab Haematol 2000;22:291-293.
3. Kent DL, Vermes D, McDonell M, Henikoff J, Fihn SD. A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Warfarin Optimal Outpatient Follow-up Study Group. Med Decis Making 1992;12:132-141.
4. Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis 1998;5 Suppl 1:19-24.
5. Horstkotte D, Piper C, Wiemer M, Schulte HD, Schultheib HP. Improvement of prognosis by home prothrombin estimation in patients with life long anticoagulation therapy. Eur Heart J 1996;17(supp):230 (abstract 1326).-
6. Ansell J, Hirsh J, Dalen J, et al. Managing oral anticoagulant therapy. Chest 2001;119(1 Suppl):22S-38S.
7. Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 2: Oral anticoagulants. American Heart Association. Circulation 1994;89:1469-1480.Erratum in Circulation. 1995; 91:A55–A56.
8. MICROMEDEX Drug Points System. Available at: www.micromedex.com. Accessed on January 8, 2005.
9. Hardman JG, Limbird LE, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.
10. Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa: WB Saunders, 2004.
11. Institute for Clinical Systems Integration. Health Care Guidelines: Anticoagulation Therapy. Supplement Management. Bloomington, Minn: ICSI; 2003.
12. Oertel LB. Managing maintenance therapy. In: Ansell JE, et al, eds. Managing Oral Anticoagulation Therapy: Clinical and Operational Guidelines. Gaithersburg, Md: Aspen; 1998.
1. Pengo V, Barbero F, Biasiolo A, Pegoraro C, Cucchini U, Iliceto S. A comparison between six- and four-week intervals in surveillance of oral anticoagulant treatment. Am J Clin Pathol 2003;120:944-947.
2. Lidstone V, Janes S, Stross P. INR: Intervals of measurement can safely extend to 14 weeks. Clin Lab Haematol 2000;22:291-293.
3. Kent DL, Vermes D, McDonell M, Henikoff J, Fihn SD. A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Warfarin Optimal Outpatient Follow-up Study Group. Med Decis Making 1992;12:132-141.
4. Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis 1998;5 Suppl 1:19-24.
5. Horstkotte D, Piper C, Wiemer M, Schulte HD, Schultheib HP. Improvement of prognosis by home prothrombin estimation in patients with life long anticoagulation therapy. Eur Heart J 1996;17(supp):230 (abstract 1326).-
6. Ansell J, Hirsh J, Dalen J, et al. Managing oral anticoagulant therapy. Chest 2001;119(1 Suppl):22S-38S.
7. Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 2: Oral anticoagulants. American Heart Association. Circulation 1994;89:1469-1480.Erratum in Circulation. 1995; 91:A55–A56.
8. MICROMEDEX Drug Points System. Available at: www.micromedex.com. Accessed on January 8, 2005.
9. Hardman JG, Limbird LE, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.
10. Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa: WB Saunders, 2004.
11. Institute for Clinical Systems Integration. Health Care Guidelines: Anticoagulation Therapy. Supplement Management. Bloomington, Minn: ICSI; 2003.
12. Oertel LB. Managing maintenance therapy. In: Ansell JE, et al, eds. Managing Oral Anticoagulation Therapy: Clinical and Operational Guidelines. Gaithersburg, Md: Aspen; 1998.
Evidence-based answers from the Family Physicians Inquiries Network