Clinical

Clinical question: Which interventions are most effective to prevent 30-day readmissions in medical or surgical patients?

Background: Preventing early readmissions has become a national priority. This study set out to determine which intervention had the largest impact on the prevention of early readmission.

Study design: Meta-analysis.

Setting: Forty-seven studies in multiple locations.

Synopsis: This study evaluated 47 randomized trials that assessed the effectiveness of peri-discharge interventions on the risk of all-cause or unplanned 30-day readmissions for medical and surgical patients. Outcomes included unplanned readmissions, all-cause readmissions, and a composite of unplanned and all-cause readmissions plus out-of-hospital deaths.

The included studies reported up to seven methods of preventing readmissions, including involvement of case management, home visits, education of patients, and self-care support. In 42 trials reporting readmission rates, the pooled relative risk of readmission was 0.82 (95 % CI, 0.73-0.91; P<0.001) within 30 days.

Multiple subgroup analyses noted that the most effective interventions on hospital readmission were those that were more complex and those that sought to augment patient capacity to access and enact dependable post-discharge care.

Limitations included single-center academic studies, lack of standard for dealing with missing data, existence of publication bias, and differing methods used to evaluate intervention effects.

Bottom line: This study was the largest of its kind, to date, and suggests that the interventions analyzed in this study, although complex (e.g. enhancing capacity for self-care at home), were efficacious in reducing 30-day readmissions.

Citation: Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107.

Clinical question: Which interventions are most effective to prevent 30-day readmissions in medical or surgical patients?

Background: Preventing early readmissions has become a national priority. This study set out to determine which intervention had the largest impact on the prevention of early readmission.

Study design: Meta-analysis.

Setting: Forty-seven studies in multiple locations.

Synopsis: This study evaluated 47 randomized trials that assessed the effectiveness of peri-discharge interventions on the risk of all-cause or unplanned 30-day readmissions for medical and surgical patients. Outcomes included unplanned readmissions, all-cause readmissions, and a composite of unplanned and all-cause readmissions plus out-of-hospital deaths.

The included studies reported up to seven methods of preventing readmissions, including involvement of case management, home visits, education of patients, and self-care support. In 42 trials reporting readmission rates, the pooled relative risk of readmission was 0.82 (95 % CI, 0.73-0.91; P<0.001) within 30 days.

Multiple subgroup analyses noted that the most effective interventions on hospital readmission were those that were more complex and those that sought to augment patient capacity to access and enact dependable post-discharge care.

Limitations included single-center academic studies, lack of standard for dealing with missing data, existence of publication bias, and differing methods used to evaluate intervention effects.

Bottom line: This study was the largest of its kind, to date, and suggests that the interventions analyzed in this study, although complex (e.g. enhancing capacity for self-care at home), were efficacious in reducing 30-day readmissions.

Citation: Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107.

Clinical question: Which interventions are most effective to prevent 30-day readmissions in medical or surgical patients?

Background: Preventing early readmissions has become a national priority. This study set out to determine which intervention had the largest impact on the prevention of early readmission.

Study design: Meta-analysis.

Setting: Forty-seven studies in multiple locations.

Synopsis: This study evaluated 47 randomized trials that assessed the effectiveness of peri-discharge interventions on the risk of all-cause or unplanned 30-day readmissions for medical and surgical patients. Outcomes included unplanned readmissions, all-cause readmissions, and a composite of unplanned and all-cause readmissions plus out-of-hospital deaths.

The included studies reported up to seven methods of preventing readmissions, including involvement of case management, home visits, education of patients, and self-care support. In 42 trials reporting readmission rates, the pooled relative risk of readmission was 0.82 (95 % CI, 0.73-0.91; P<0.001) within 30 days.

Multiple subgroup analyses noted that the most effective interventions on hospital readmission were those that were more complex and those that sought to augment patient capacity to access and enact dependable post-discharge care.

Limitations included single-center academic studies, lack of standard for dealing with missing data, existence of publication bias, and differing methods used to evaluate intervention effects.

Bottom line: This study was the largest of its kind, to date, and suggests that the interventions analyzed in this study, although complex (e.g. enhancing capacity for self-care at home), were efficacious in reducing 30-day readmissions.

Citation: Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107.

Case

A 77-year-old woman with a history of stroke five months prior, bileaflet aortic valve prosthesis, hypertension, and insulin-dependent diabetes is admitted for laparoscopy with lysis of adhesions. The patient stopped her warfarin 10 days prior to admission and initiated enoxaparin five days later. When should the enoxaparin be discontinued?

Intra-operatively, the surgeon converted the case to an open laparotomy for a bowel resection with re-anastomosis; post-operatively, when should the hospitalist reinitiate warfarin and enoxaparin?

Background

Many patients receive chronic oral anticoagulant therapy to minimize their long-term risk of thromboembolic disease. Hospitalists and outpatient providers often care for such patients who need to undergo a medical procedure or operation. The risk of bleeding associated with the medical procedure necessitates an interruption in the patient’s chronic oral anticoagulant therapy. In this scenario, providers are faced with several therapeutic decisions:

• How soon before the procedure should patients stop taking oral anticoagulant?
• During the period of time when the patient is not taking chronic oral anticoagulant, should the patient receive parenteral bridging anticoagulant therapy?
• After the procedure, when should patients restart chronic oral anticoagulant therapy?

‘Bridge’ anticoagulant therapy is the administration of a short-acting parenteral anticoagulant during the peri-operative period, when the patient is not taking chronic oral anticoagulant.¹ The intent of bridge anticoagulant therapy is to minimize both the risk of thromboembolic events and the risk of bleeding during the peri-operative period. Bridging anticoagulant therapy is appropriate for some but not all patients undergoing medical procedures.

The Data

When to discontinue warfarin? Warfarin, the most commonly prescribed oral anticoagulant, achieves its therapeutic effects by antagonizing the actions of endogenous vitamin K-dependent coagulation factors. The decision on when to stop warfarin prior to surgery is dependent on the regeneration time of coagulation factors following the discontinuation of warfarin therapy. Although warfarin’s half-life is typically 36-42 hours, its therapeutic effects typically last up to five days in healthy subjects and often longer in elderly patients.²

Current guidelines recommend the discontinuation of warfarin at least five days prior to surgery (Grade 1C recommendation).³ Despite this recommendation, approximately 7% of patients will still have an international normalized ratio (INR) >1.5 after not taking warfarin for five days.⁴ For this reason, the guidelines recommend that all patients have their INR checked on the day of surgery. For those patients with an INR of 1.5 to 1.9 on the day prior to surgery, there is evidence to show that administration of 1 mg of vitamin K will lower the INR to 1.4 in greater than 90% of cases.⁵

Assessment of peri-procedural thrombotic risk. Knowledge of a patient’s past medical history is critical in helping providers stratify the patient’s peri-procedural thrombotic risk. According to the 2012 American College of Chest Physicians (ACCP) guidelines, a history of atrial fibrillation (Afib), mechanical heart valve(s), and previous VTE are independent risk factors for peri-procedural thrombotic events.³ Hospitalists may risk-stratify their patients based on the anticipated annualized rate of thrombosis or embolization: <5%, 5%-10%, or >15% for the respective low, medium, and high-risk groups.⁶

Patients with Afib history. For these patients, the CHADS2 score helps to stratify the risk of peri-procedural thrombosis. Low risk is defined as a CHADS2 score of zero to two, assuming that the two points were not scored for transient ischemic attack (TIA) or cerebrovascular accident (CVA). Any patient with a TIA or CVA within the previous three months is automatically considered high risk. Medium risk is a score of three or four.

In addition to the aforementioned TIA or CVA within the prior three months, high-risk patients also include those with a CHADS2 score of five or six or any patient with a history of rheumatic heart disease.³ Patients with CHADS2 scores less than five but with a TIA or CVA greater than three months in the past are high risk.⁷

Presence of mechanical heart valve(s). For patients with a mechanical heart valve, knowledge of the valve type and location is essential to assist hospitalists in stratifying the risk of peri-procedural thrombosis. The current ACCP guidelines consider patients with bileaflet aortic valve prostheses without additional risk factors for stroke or atrial fibrillation to be low risk.³

The guidelines define the following characteristics as medium risk for patients: the presence of a bileaflet valve with additional risk factors for stroke such as atrial fibrillation, age greater than 75, prior CVA (more than six months prior), hypertension, diabetes mellitus, or congestive heart failure.

Patients at high risk include those with aortic valve prosthesis with a caged-ball or tilting disc, patients with mitral valve prosthesis, and those with a mechanical valve with CVA or TIA during the prior six months.⁷

History of previous VTE. For these patients, the duration of time that has passed since their last VTE event is an important factor in helping to stratify their risk for peri-procedural thrombosis. Hospitalists should consider patients low risk if they had VTE more than one year prior to the procedure.

Medium-risk patients are those with VTE events in the preceding three to twelve months, those with recurrent VTE, those with active cancer who have received cancer therapy within six months, or patients with non-severe thrombophilias (e.g. heterogenous factor V Leiden or prothrombin gene mutation).

Hospitalists should identify high-risk patients as those with VTE that has occurred within three months or those with severe thrombophilias such as Protein C or S deficiency, antithrombin III deficiency, or antiphospholipid antibody syndrome.

Assessment of procedure-related thrombotic risk. The type of anticipated procedure itself conveys peri-procedural thrombotic risk. For example, heart valve replacement, carotid endarterectomy, or other major vascular surgeries automatically stratify patients in the high-risk category, regardless of underlying medication condition.

Assessment of bleeding risk. Hospitalists must identify any preexisting bleeding risk factors (i.e., hemophilias or thrombocytopenia) in addition to the post-procedural bleeding risks. Risk factors for increased post-procedural bleeding include: major surgery with extensive tissue injury, procedures involving highly vascularized organs, removal of large colonic polyps, urological procedures, placement of implantable cardioverter-defibrillator/pacemakers, and procedures at sites where minor bleeding would be clinically devastating, such as the brain or spine.³

Thus, communication with the proceduralist or surgeon regarding the anticipated bleeding risk is vital.

Should the patient receive bridging anticoagulation? Patients considered high risk for peri-procedural thrombosis should receive peri-procedural bridging anticoagulation therapy, while those considered low risk should not. For patients with a moderate peri-procedural risk of thrombosis, hospitalists should base the decision on individual and anticipated pre-surgical/procedural thrombotic risks.

Recent evidence suggests that bridging anticoagulation should be avoided in patients undergoing procedures with high bleeding risk who are not at high thromboembolic risk.⁸

Selection and pre-operative discontinuation of bridging medication. Current ACCP guidelines only support the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) as bridging anticoagulants.³ Evidence supports the use of either intravenous UFH (goal aPTT 1.5 to two times control aPTT) or enoxaparin (1 mg/kg BID or 1.5 mg/kg once daily).⁹ UFH is preferred over LMWH in patients with chronic kidney disease stage IV or V due to a more predictable pharmacokinetic profile.

Clinicians should initiate a bridge when a patient’s INR falls to less than 2.0 and discontinue the UFH bridge four to six hours prior to the procedure.¹⁰ The recent update to the guidelines now states that LMWH should be discontinued 24, instead of 12, hours prior to the procedure.³

When to restart UHF or LMWH bridge post-procedure. The type of procedure being performed dictates when bridging anticoagulation should resume. In patients who have undergone surgeries that involve high bleeding risk, LMWH should not be administered until 48-72 hours post-surgery (Grade 2C evidence).³ For those patients undergoing surgeries with low bleeding risk, bridging should be resumed approximately 24 hours after the procedure.

Of note, enoxaparin administered in one single daily dose, as compared to divided doses, is associated with a greater risk of post-operative bleeding. UFH bridging should resume post-operatively without a bolus dose at 24 hours in low-risk bleeding cases or 48-72 hours in high-risk bleeding cases (Grade 2C evidence).³

On occasion, unanticipated adjustments to surgical cases—or complications—change the previously determined post-operative bleeding risk. In these instances, the hospitalist and surgeon/proceduralist should review the case and reassess the bleeding risk prior to employing bridging anticoagulation protocols.

When to restart long-term vitamin K antagonists (VKA) post-procedure. In most instances, regardless of pre-operative bleeding risk stratification, the resumption of VKA may occur once post-operative hemostasis has been achieved and the patient has been instructed to resume eating by the proceduralist or surgeon. This most often occurs on the calendar day following surgery, because it takes approximately five days for an INR to achieve therapeutic levels.

Back to the Case

The patient’s history of prosthetic valve with stroke within the preceding six months stratified her to a high thrombotic risk category. Given the high risk of thrombosis, the decision was made to bridge with LMWH. The hospitalist discontinued LMWH 24 hours prior to surgery, and INR was checked on the morning of the procedure.

Although the patient underwent the operation without significant bleeding, the adjustment from an exploratory laparoscopy to an open laparotomy increased her post-operative bleeding risk from medium to high. Therefore, bridging anticoagulation with LMWH was resumed no sooner than 48 hours after the operation. Her warfarin was restarted on the day following surgery, once she resumed her diet.

Bottom Line

Hospitalists must understand both the pre- and post-procedure thrombotic risks, as well as the pre- and post-procedural bleeding risks, when determining the selection and logistics of initiation and cessation of antithrombotic bridging for inpatients.

Drs. McCormick, Carbo, and Li are hospitalists at Beth Israel Deaconess Medical Center in Boston. Dr. Kerbel is a hospitalist at the University of California Los Angeles.

References

1. BRIDGE Study Investigators. Bridging anticoagulation: is it needed when warfarin is interrupted around the time of a surgery or procedure? Circulation. 2012;125(12):e496-498.
2. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
3. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-350S.
4. Kovacs MJ, Kearon C, Rodger M, et al. Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation. 2004;110(12):1658-1663.
5. Woods K, Douketis JD, Kathirgamanathan K, Yi Q, Crowther MA. Low-dose oral vitamin K to normalize the international normalized ratio prior to surgery in patients who require temporary interruption of warfarin. J Thromb Thrombolysis. 2007;24(2):93-97.
6. Ortel TL. Perioperative management of patients on chronic antithrombotic therapy. Blood. 2012;120(24):4699-4705.
7. Kaatz S, Douketis JD, Zhou H, Gage BF, White RH. Risk of stroke after surgery in patients with and without chronic atrial fibrillation. J Thromb Haemost. 2010;8(5):884-890.
8. Siegal D, Yudin J, Kaatz S, Douketis JD, Lim W, Spyropoulos AC. Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation. 2012;126(13):1630-1639.
9. Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146-153.
10. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):188S-203S.

Case

A 77-year-old woman with a history of stroke five months prior, bileaflet aortic valve prosthesis, hypertension, and insulin-dependent diabetes is admitted for laparoscopy with lysis of adhesions. The patient stopped her warfarin 10 days prior to admission and initiated enoxaparin five days later. When should the enoxaparin be discontinued?

Intra-operatively, the surgeon converted the case to an open laparotomy for a bowel resection with re-anastomosis; post-operatively, when should the hospitalist reinitiate warfarin and enoxaparin?

Background

Many patients receive chronic oral anticoagulant therapy to minimize their long-term risk of thromboembolic disease. Hospitalists and outpatient providers often care for such patients who need to undergo a medical procedure or operation. The risk of bleeding associated with the medical procedure necessitates an interruption in the patient’s chronic oral anticoagulant therapy. In this scenario, providers are faced with several therapeutic decisions:

• How soon before the procedure should patients stop taking oral anticoagulant?
• During the period of time when the patient is not taking chronic oral anticoagulant, should the patient receive parenteral bridging anticoagulant therapy?
• After the procedure, when should patients restart chronic oral anticoagulant therapy?

‘Bridge’ anticoagulant therapy is the administration of a short-acting parenteral anticoagulant during the peri-operative period, when the patient is not taking chronic oral anticoagulant.¹ The intent of bridge anticoagulant therapy is to minimize both the risk of thromboembolic events and the risk of bleeding during the peri-operative period. Bridging anticoagulant therapy is appropriate for some but not all patients undergoing medical procedures.

The Data

When to discontinue warfarin? Warfarin, the most commonly prescribed oral anticoagulant, achieves its therapeutic effects by antagonizing the actions of endogenous vitamin K-dependent coagulation factors. The decision on when to stop warfarin prior to surgery is dependent on the regeneration time of coagulation factors following the discontinuation of warfarin therapy. Although warfarin’s half-life is typically 36-42 hours, its therapeutic effects typically last up to five days in healthy subjects and often longer in elderly patients.²

Current guidelines recommend the discontinuation of warfarin at least five days prior to surgery (Grade 1C recommendation).³ Despite this recommendation, approximately 7% of patients will still have an international normalized ratio (INR) >1.5 after not taking warfarin for five days.⁴ For this reason, the guidelines recommend that all patients have their INR checked on the day of surgery. For those patients with an INR of 1.5 to 1.9 on the day prior to surgery, there is evidence to show that administration of 1 mg of vitamin K will lower the INR to 1.4 in greater than 90% of cases.⁵

Assessment of peri-procedural thrombotic risk. Knowledge of a patient’s past medical history is critical in helping providers stratify the patient’s peri-procedural thrombotic risk. According to the 2012 American College of Chest Physicians (ACCP) guidelines, a history of atrial fibrillation (Afib), mechanical heart valve(s), and previous VTE are independent risk factors for peri-procedural thrombotic events.³ Hospitalists may risk-stratify their patients based on the anticipated annualized rate of thrombosis or embolization: <5%, 5%-10%, or >15% for the respective low, medium, and high-risk groups.⁶

Patients with Afib history. For these patients, the CHADS2 score helps to stratify the risk of peri-procedural thrombosis. Low risk is defined as a CHADS2 score of zero to two, assuming that the two points were not scored for transient ischemic attack (TIA) or cerebrovascular accident (CVA). Any patient with a TIA or CVA within the previous three months is automatically considered high risk. Medium risk is a score of three or four.

In addition to the aforementioned TIA or CVA within the prior three months, high-risk patients also include those with a CHADS2 score of five or six or any patient with a history of rheumatic heart disease.³ Patients with CHADS2 scores less than five but with a TIA or CVA greater than three months in the past are high risk.⁷

Presence of mechanical heart valve(s). For patients with a mechanical heart valve, knowledge of the valve type and location is essential to assist hospitalists in stratifying the risk of peri-procedural thrombosis. The current ACCP guidelines consider patients with bileaflet aortic valve prostheses without additional risk factors for stroke or atrial fibrillation to be low risk.³

The guidelines define the following characteristics as medium risk for patients: the presence of a bileaflet valve with additional risk factors for stroke such as atrial fibrillation, age greater than 75, prior CVA (more than six months prior), hypertension, diabetes mellitus, or congestive heart failure.

Patients at high risk include those with aortic valve prosthesis with a caged-ball or tilting disc, patients with mitral valve prosthesis, and those with a mechanical valve with CVA or TIA during the prior six months.⁷

History of previous VTE. For these patients, the duration of time that has passed since their last VTE event is an important factor in helping to stratify their risk for peri-procedural thrombosis. Hospitalists should consider patients low risk if they had VTE more than one year prior to the procedure.

Medium-risk patients are those with VTE events in the preceding three to twelve months, those with recurrent VTE, those with active cancer who have received cancer therapy within six months, or patients with non-severe thrombophilias (e.g. heterogenous factor V Leiden or prothrombin gene mutation).

Hospitalists should identify high-risk patients as those with VTE that has occurred within three months or those with severe thrombophilias such as Protein C or S deficiency, antithrombin III deficiency, or antiphospholipid antibody syndrome.

Assessment of procedure-related thrombotic risk. The type of anticipated procedure itself conveys peri-procedural thrombotic risk. For example, heart valve replacement, carotid endarterectomy, or other major vascular surgeries automatically stratify patients in the high-risk category, regardless of underlying medication condition.

Assessment of bleeding risk. Hospitalists must identify any preexisting bleeding risk factors (i.e., hemophilias or thrombocytopenia) in addition to the post-procedural bleeding risks. Risk factors for increased post-procedural bleeding include: major surgery with extensive tissue injury, procedures involving highly vascularized organs, removal of large colonic polyps, urological procedures, placement of implantable cardioverter-defibrillator/pacemakers, and procedures at sites where minor bleeding would be clinically devastating, such as the brain or spine.³

Thus, communication with the proceduralist or surgeon regarding the anticipated bleeding risk is vital.

Should the patient receive bridging anticoagulation? Patients considered high risk for peri-procedural thrombosis should receive peri-procedural bridging anticoagulation therapy, while those considered low risk should not. For patients with a moderate peri-procedural risk of thrombosis, hospitalists should base the decision on individual and anticipated pre-surgical/procedural thrombotic risks.

Recent evidence suggests that bridging anticoagulation should be avoided in patients undergoing procedures with high bleeding risk who are not at high thromboembolic risk.⁸

Selection and pre-operative discontinuation of bridging medication. Current ACCP guidelines only support the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) as bridging anticoagulants.³ Evidence supports the use of either intravenous UFH (goal aPTT 1.5 to two times control aPTT) or enoxaparin (1 mg/kg BID or 1.5 mg/kg once daily).⁹ UFH is preferred over LMWH in patients with chronic kidney disease stage IV or V due to a more predictable pharmacokinetic profile.

Clinicians should initiate a bridge when a patient’s INR falls to less than 2.0 and discontinue the UFH bridge four to six hours prior to the procedure.¹⁰ The recent update to the guidelines now states that LMWH should be discontinued 24, instead of 12, hours prior to the procedure.³

When to restart UHF or LMWH bridge post-procedure. The type of procedure being performed dictates when bridging anticoagulation should resume. In patients who have undergone surgeries that involve high bleeding risk, LMWH should not be administered until 48-72 hours post-surgery (Grade 2C evidence).³ For those patients undergoing surgeries with low bleeding risk, bridging should be resumed approximately 24 hours after the procedure.

Of note, enoxaparin administered in one single daily dose, as compared to divided doses, is associated with a greater risk of post-operative bleeding. UFH bridging should resume post-operatively without a bolus dose at 24 hours in low-risk bleeding cases or 48-72 hours in high-risk bleeding cases (Grade 2C evidence).³

On occasion, unanticipated adjustments to surgical cases—or complications—change the previously determined post-operative bleeding risk. In these instances, the hospitalist and surgeon/proceduralist should review the case and reassess the bleeding risk prior to employing bridging anticoagulation protocols.

When to restart long-term vitamin K antagonists (VKA) post-procedure. In most instances, regardless of pre-operative bleeding risk stratification, the resumption of VKA may occur once post-operative hemostasis has been achieved and the patient has been instructed to resume eating by the proceduralist or surgeon. This most often occurs on the calendar day following surgery, because it takes approximately five days for an INR to achieve therapeutic levels.

Back to the Case

The patient’s history of prosthetic valve with stroke within the preceding six months stratified her to a high thrombotic risk category. Given the high risk of thrombosis, the decision was made to bridge with LMWH. The hospitalist discontinued LMWH 24 hours prior to surgery, and INR was checked on the morning of the procedure.

Although the patient underwent the operation without significant bleeding, the adjustment from an exploratory laparoscopy to an open laparotomy increased her post-operative bleeding risk from medium to high. Therefore, bridging anticoagulation with LMWH was resumed no sooner than 48 hours after the operation. Her warfarin was restarted on the day following surgery, once she resumed her diet.

Bottom Line

Hospitalists must understand both the pre- and post-procedure thrombotic risks, as well as the pre- and post-procedural bleeding risks, when determining the selection and logistics of initiation and cessation of antithrombotic bridging for inpatients.

Drs. McCormick, Carbo, and Li are hospitalists at Beth Israel Deaconess Medical Center in Boston. Dr. Kerbel is a hospitalist at the University of California Los Angeles.

References

1. BRIDGE Study Investigators. Bridging anticoagulation: is it needed when warfarin is interrupted around the time of a surgery or procedure? Circulation. 2012;125(12):e496-498.
2. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
3. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-350S.
4. Kovacs MJ, Kearon C, Rodger M, et al. Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation. 2004;110(12):1658-1663.
5. Woods K, Douketis JD, Kathirgamanathan K, Yi Q, Crowther MA. Low-dose oral vitamin K to normalize the international normalized ratio prior to surgery in patients who require temporary interruption of warfarin. J Thromb Thrombolysis. 2007;24(2):93-97.
6. Ortel TL. Perioperative management of patients on chronic antithrombotic therapy. Blood. 2012;120(24):4699-4705.
7. Kaatz S, Douketis JD, Zhou H, Gage BF, White RH. Risk of stroke after surgery in patients with and without chronic atrial fibrillation. J Thromb Haemost. 2010;8(5):884-890.
8. Siegal D, Yudin J, Kaatz S, Douketis JD, Lim W, Spyropoulos AC. Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation. 2012;126(13):1630-1639.
9. Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146-153.
10. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):188S-203S.

Case

A 77-year-old woman with a history of stroke five months prior, bileaflet aortic valve prosthesis, hypertension, and insulin-dependent diabetes is admitted for laparoscopy with lysis of adhesions. The patient stopped her warfarin 10 days prior to admission and initiated enoxaparin five days later. When should the enoxaparin be discontinued?

Intra-operatively, the surgeon converted the case to an open laparotomy for a bowel resection with re-anastomosis; post-operatively, when should the hospitalist reinitiate warfarin and enoxaparin?

Background

Many patients receive chronic oral anticoagulant therapy to minimize their long-term risk of thromboembolic disease. Hospitalists and outpatient providers often care for such patients who need to undergo a medical procedure or operation. The risk of bleeding associated with the medical procedure necessitates an interruption in the patient’s chronic oral anticoagulant therapy. In this scenario, providers are faced with several therapeutic decisions:

• How soon before the procedure should patients stop taking oral anticoagulant?
• During the period of time when the patient is not taking chronic oral anticoagulant, should the patient receive parenteral bridging anticoagulant therapy?
• After the procedure, when should patients restart chronic oral anticoagulant therapy?

‘Bridge’ anticoagulant therapy is the administration of a short-acting parenteral anticoagulant during the peri-operative period, when the patient is not taking chronic oral anticoagulant.¹ The intent of bridge anticoagulant therapy is to minimize both the risk of thromboembolic events and the risk of bleeding during the peri-operative period. Bridging anticoagulant therapy is appropriate for some but not all patients undergoing medical procedures.

The Data

When to discontinue warfarin? Warfarin, the most commonly prescribed oral anticoagulant, achieves its therapeutic effects by antagonizing the actions of endogenous vitamin K-dependent coagulation factors. The decision on when to stop warfarin prior to surgery is dependent on the regeneration time of coagulation factors following the discontinuation of warfarin therapy. Although warfarin’s half-life is typically 36-42 hours, its therapeutic effects typically last up to five days in healthy subjects and often longer in elderly patients.²

Current guidelines recommend the discontinuation of warfarin at least five days prior to surgery (Grade 1C recommendation).³ Despite this recommendation, approximately 7% of patients will still have an international normalized ratio (INR) >1.5 after not taking warfarin for five days.⁴ For this reason, the guidelines recommend that all patients have their INR checked on the day of surgery. For those patients with an INR of 1.5 to 1.9 on the day prior to surgery, there is evidence to show that administration of 1 mg of vitamin K will lower the INR to 1.4 in greater than 90% of cases.⁵

Assessment of peri-procedural thrombotic risk. Knowledge of a patient’s past medical history is critical in helping providers stratify the patient’s peri-procedural thrombotic risk. According to the 2012 American College of Chest Physicians (ACCP) guidelines, a history of atrial fibrillation (Afib), mechanical heart valve(s), and previous VTE are independent risk factors for peri-procedural thrombotic events.³ Hospitalists may risk-stratify their patients based on the anticipated annualized rate of thrombosis or embolization: <5%, 5%-10%, or >15% for the respective low, medium, and high-risk groups.⁶

Patients with Afib history. For these patients, the CHADS2 score helps to stratify the risk of peri-procedural thrombosis. Low risk is defined as a CHADS2 score of zero to two, assuming that the two points were not scored for transient ischemic attack (TIA) or cerebrovascular accident (CVA). Any patient with a TIA or CVA within the previous three months is automatically considered high risk. Medium risk is a score of three or four.

In addition to the aforementioned TIA or CVA within the prior three months, high-risk patients also include those with a CHADS2 score of five or six or any patient with a history of rheumatic heart disease.³ Patients with CHADS2 scores less than five but with a TIA or CVA greater than three months in the past are high risk.⁷

Presence of mechanical heart valve(s). For patients with a mechanical heart valve, knowledge of the valve type and location is essential to assist hospitalists in stratifying the risk of peri-procedural thrombosis. The current ACCP guidelines consider patients with bileaflet aortic valve prostheses without additional risk factors for stroke or atrial fibrillation to be low risk.³

The guidelines define the following characteristics as medium risk for patients: the presence of a bileaflet valve with additional risk factors for stroke such as atrial fibrillation, age greater than 75, prior CVA (more than six months prior), hypertension, diabetes mellitus, or congestive heart failure.

Patients at high risk include those with aortic valve prosthesis with a caged-ball or tilting disc, patients with mitral valve prosthesis, and those with a mechanical valve with CVA or TIA during the prior six months.⁷

History of previous VTE. For these patients, the duration of time that has passed since their last VTE event is an important factor in helping to stratify their risk for peri-procedural thrombosis. Hospitalists should consider patients low risk if they had VTE more than one year prior to the procedure.

Medium-risk patients are those with VTE events in the preceding three to twelve months, those with recurrent VTE, those with active cancer who have received cancer therapy within six months, or patients with non-severe thrombophilias (e.g. heterogenous factor V Leiden or prothrombin gene mutation).

Hospitalists should identify high-risk patients as those with VTE that has occurred within three months or those with severe thrombophilias such as Protein C or S deficiency, antithrombin III deficiency, or antiphospholipid antibody syndrome.

Assessment of procedure-related thrombotic risk. The type of anticipated procedure itself conveys peri-procedural thrombotic risk. For example, heart valve replacement, carotid endarterectomy, or other major vascular surgeries automatically stratify patients in the high-risk category, regardless of underlying medication condition.

Assessment of bleeding risk. Hospitalists must identify any preexisting bleeding risk factors (i.e., hemophilias or thrombocytopenia) in addition to the post-procedural bleeding risks. Risk factors for increased post-procedural bleeding include: major surgery with extensive tissue injury, procedures involving highly vascularized organs, removal of large colonic polyps, urological procedures, placement of implantable cardioverter-defibrillator/pacemakers, and procedures at sites where minor bleeding would be clinically devastating, such as the brain or spine.³

Thus, communication with the proceduralist or surgeon regarding the anticipated bleeding risk is vital.

Should the patient receive bridging anticoagulation? Patients considered high risk for peri-procedural thrombosis should receive peri-procedural bridging anticoagulation therapy, while those considered low risk should not. For patients with a moderate peri-procedural risk of thrombosis, hospitalists should base the decision on individual and anticipated pre-surgical/procedural thrombotic risks.

Recent evidence suggests that bridging anticoagulation should be avoided in patients undergoing procedures with high bleeding risk who are not at high thromboembolic risk.⁸

Selection and pre-operative discontinuation of bridging medication. Current ACCP guidelines only support the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) as bridging anticoagulants.³ Evidence supports the use of either intravenous UFH (goal aPTT 1.5 to two times control aPTT) or enoxaparin (1 mg/kg BID or 1.5 mg/kg once daily).⁹ UFH is preferred over LMWH in patients with chronic kidney disease stage IV or V due to a more predictable pharmacokinetic profile.

Clinicians should initiate a bridge when a patient’s INR falls to less than 2.0 and discontinue the UFH bridge four to six hours prior to the procedure.¹⁰ The recent update to the guidelines now states that LMWH should be discontinued 24, instead of 12, hours prior to the procedure.³

When to restart UHF or LMWH bridge post-procedure. The type of procedure being performed dictates when bridging anticoagulation should resume. In patients who have undergone surgeries that involve high bleeding risk, LMWH should not be administered until 48-72 hours post-surgery (Grade 2C evidence).³ For those patients undergoing surgeries with low bleeding risk, bridging should be resumed approximately 24 hours after the procedure.

Of note, enoxaparin administered in one single daily dose, as compared to divided doses, is associated with a greater risk of post-operative bleeding. UFH bridging should resume post-operatively without a bolus dose at 24 hours in low-risk bleeding cases or 48-72 hours in high-risk bleeding cases (Grade 2C evidence).³

On occasion, unanticipated adjustments to surgical cases—or complications—change the previously determined post-operative bleeding risk. In these instances, the hospitalist and surgeon/proceduralist should review the case and reassess the bleeding risk prior to employing bridging anticoagulation protocols.

When to restart long-term vitamin K antagonists (VKA) post-procedure. In most instances, regardless of pre-operative bleeding risk stratification, the resumption of VKA may occur once post-operative hemostasis has been achieved and the patient has been instructed to resume eating by the proceduralist or surgeon. This most often occurs on the calendar day following surgery, because it takes approximately five days for an INR to achieve therapeutic levels.

Back to the Case

The patient’s history of prosthetic valve with stroke within the preceding six months stratified her to a high thrombotic risk category. Given the high risk of thrombosis, the decision was made to bridge with LMWH. The hospitalist discontinued LMWH 24 hours prior to surgery, and INR was checked on the morning of the procedure.

Although the patient underwent the operation without significant bleeding, the adjustment from an exploratory laparoscopy to an open laparotomy increased her post-operative bleeding risk from medium to high. Therefore, bridging anticoagulation with LMWH was resumed no sooner than 48 hours after the operation. Her warfarin was restarted on the day following surgery, once she resumed her diet.

Bottom Line

Hospitalists must understand both the pre- and post-procedure thrombotic risks, as well as the pre- and post-procedural bleeding risks, when determining the selection and logistics of initiation and cessation of antithrombotic bridging for inpatients.

Drs. McCormick, Carbo, and Li are hospitalists at Beth Israel Deaconess Medical Center in Boston. Dr. Kerbel is a hospitalist at the University of California Los Angeles.

References

1. BRIDGE Study Investigators. Bridging anticoagulation: is it needed when warfarin is interrupted around the time of a surgery or procedure? Circulation. 2012;125(12):e496-498.
2. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
3. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-350S.
4. Kovacs MJ, Kearon C, Rodger M, et al. Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation. 2004;110(12):1658-1663.
5. Woods K, Douketis JD, Kathirgamanathan K, Yi Q, Crowther MA. Low-dose oral vitamin K to normalize the international normalized ratio prior to surgery in patients who require temporary interruption of warfarin. J Thromb Thrombolysis. 2007;24(2):93-97.
6. Ortel TL. Perioperative management of patients on chronic antithrombotic therapy. Blood. 2012;120(24):4699-4705.
7. Kaatz S, Douketis JD, Zhou H, Gage BF, White RH. Risk of stroke after surgery in patients with and without chronic atrial fibrillation. J Thromb Haemost. 2010;8(5):884-890.
8. Siegal D, Yudin J, Kaatz S, Douketis JD, Lim W, Spyropoulos AC. Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation. 2012;126(13):1630-1639.
9. Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146-153.
10. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):188S-203S.

Weijen Chang, MD, SFHM, FAAP

Clinical question: Are clinical outcomes for dexamethasone equivalent to currently recommended corticosteroids for the treatment of children with mild to moderate asthma exacerbations?

Background: National and international guidelines uniformly agree that administration of a systemic corticosteroid is appropriate for children hospitalized with mild to moderate asthma exacerbations. Based on available literature, a 2007 update to an expert panel report developed by the National Asthma Education and Prevention Program recommended prednisone, methylprednisolone, or prednisolone at 1-2 mg/kg daily in two divided doses (maximum 60 mg/day).

Recent small studies have begun to examine the use of dexamethasone in acute asthma exacerbations. The longer half-life of dexamethasone enables shorter treatment regimens, which can improve compliance. Additionally, its taste is considered superior compared to currently recommended corticosteroids.

Study designs: Two meta-analyses of randomized controlled trials (RCT).

Setting: Six RCTs published between 1997 and 2008.

Synopsis: Both groups searched Medline for RCTs using the search terms “dexamethasone” and “asthma”; additional search terms included “decadron” and “status asthmaticus.” Limiting the search to a pediatric population was achieved by either using appropriate medical subject heading terms or by using an age limiter of ≤18 years of age.

Both groups performed meta-analyses of clinical outcomes, including rates of revisit to a healthcare provider and symptomatic improvement. Adverse effects, specifically vomiting, also underwent meta-analysis by both groups.

Interestingly, both groups analyzed the same six studies, and all six studies were in the ED setting. The dexamethasone regimens in the analyzed studies included single-dose intramuscular (0.3-1.7 mg/kg), single-dose oral (0.6 mg/kg), or two-dose (0.6 mg/kg/day given once daily) oral regimens. These were compared to three- or five-day regimens of prednisone or prednisolone. Not surprisingly, both groups reached similar conclusions.

Regarding symptomatic improvement and revisit rates, there was no significant difference between dexamethasone and prednisone/prednisolone groups. Vomiting was less likely in the dexamethasone groups overall.

Bottom line: Meta-analyses of small RCTs examining dexamethasone in the treatment of acute asthma exacerbations show that it is equivalent to prednisone/prednisolone in symptomatic improvement and risk of revisit, and possibly superior with regard to the risk of vomiting.

Citations: Meyer JS, Riese J, Biondi E. Is dexamethasone an effective alternative to oral prednisone in the treatment of pediatric asthma exacerbations? Hosp Pediatr. 2014;4(3):172-180. Keeney GE, Gray MP, Morrison AK. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493-499.

Reviewed by Pediatric Editor Weijen Chang, MD, SFHM, FAAP, associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital.

Weijen Chang, MD, SFHM, FAAP

Clinical question: Are clinical outcomes for dexamethasone equivalent to currently recommended corticosteroids for the treatment of children with mild to moderate asthma exacerbations?

Background: National and international guidelines uniformly agree that administration of a systemic corticosteroid is appropriate for children hospitalized with mild to moderate asthma exacerbations. Based on available literature, a 2007 update to an expert panel report developed by the National Asthma Education and Prevention Program recommended prednisone, methylprednisolone, or prednisolone at 1-2 mg/kg daily in two divided doses (maximum 60 mg/day).

Recent small studies have begun to examine the use of dexamethasone in acute asthma exacerbations. The longer half-life of dexamethasone enables shorter treatment regimens, which can improve compliance. Additionally, its taste is considered superior compared to currently recommended corticosteroids.

Study designs: Two meta-analyses of randomized controlled trials (RCT).

Setting: Six RCTs published between 1997 and 2008.

Synopsis: Both groups searched Medline for RCTs using the search terms “dexamethasone” and “asthma”; additional search terms included “decadron” and “status asthmaticus.” Limiting the search to a pediatric population was achieved by either using appropriate medical subject heading terms or by using an age limiter of ≤18 years of age.

Both groups performed meta-analyses of clinical outcomes, including rates of revisit to a healthcare provider and symptomatic improvement. Adverse effects, specifically vomiting, also underwent meta-analysis by both groups.

Interestingly, both groups analyzed the same six studies, and all six studies were in the ED setting. The dexamethasone regimens in the analyzed studies included single-dose intramuscular (0.3-1.7 mg/kg), single-dose oral (0.6 mg/kg), or two-dose (0.6 mg/kg/day given once daily) oral regimens. These were compared to three- or five-day regimens of prednisone or prednisolone. Not surprisingly, both groups reached similar conclusions.

Regarding symptomatic improvement and revisit rates, there was no significant difference between dexamethasone and prednisone/prednisolone groups. Vomiting was less likely in the dexamethasone groups overall.

Bottom line: Meta-analyses of small RCTs examining dexamethasone in the treatment of acute asthma exacerbations show that it is equivalent to prednisone/prednisolone in symptomatic improvement and risk of revisit, and possibly superior with regard to the risk of vomiting.

Citations: Meyer JS, Riese J, Biondi E. Is dexamethasone an effective alternative to oral prednisone in the treatment of pediatric asthma exacerbations? Hosp Pediatr. 2014;4(3):172-180. Keeney GE, Gray MP, Morrison AK. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493-499.

Reviewed by Pediatric Editor Weijen Chang, MD, SFHM, FAAP, associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital.

Weijen Chang, MD, SFHM, FAAP

Clinical question: Are clinical outcomes for dexamethasone equivalent to currently recommended corticosteroids for the treatment of children with mild to moderate asthma exacerbations?

Background: National and international guidelines uniformly agree that administration of a systemic corticosteroid is appropriate for children hospitalized with mild to moderate asthma exacerbations. Based on available literature, a 2007 update to an expert panel report developed by the National Asthma Education and Prevention Program recommended prednisone, methylprednisolone, or prednisolone at 1-2 mg/kg daily in two divided doses (maximum 60 mg/day).

Recent small studies have begun to examine the use of dexamethasone in acute asthma exacerbations. The longer half-life of dexamethasone enables shorter treatment regimens, which can improve compliance. Additionally, its taste is considered superior compared to currently recommended corticosteroids.

Study designs: Two meta-analyses of randomized controlled trials (RCT).

Setting: Six RCTs published between 1997 and 2008.

Synopsis: Both groups searched Medline for RCTs using the search terms “dexamethasone” and “asthma”; additional search terms included “decadron” and “status asthmaticus.” Limiting the search to a pediatric population was achieved by either using appropriate medical subject heading terms or by using an age limiter of ≤18 years of age.

Both groups performed meta-analyses of clinical outcomes, including rates of revisit to a healthcare provider and symptomatic improvement. Adverse effects, specifically vomiting, also underwent meta-analysis by both groups.

Interestingly, both groups analyzed the same six studies, and all six studies were in the ED setting. The dexamethasone regimens in the analyzed studies included single-dose intramuscular (0.3-1.7 mg/kg), single-dose oral (0.6 mg/kg), or two-dose (0.6 mg/kg/day given once daily) oral regimens. These were compared to three- or five-day regimens of prednisone or prednisolone. Not surprisingly, both groups reached similar conclusions.

Regarding symptomatic improvement and revisit rates, there was no significant difference between dexamethasone and prednisone/prednisolone groups. Vomiting was less likely in the dexamethasone groups overall.

Bottom line: Meta-analyses of small RCTs examining dexamethasone in the treatment of acute asthma exacerbations show that it is equivalent to prednisone/prednisolone in symptomatic improvement and risk of revisit, and possibly superior with regard to the risk of vomiting.

Citations: Meyer JS, Riese J, Biondi E. Is dexamethasone an effective alternative to oral prednisone in the treatment of pediatric asthma exacerbations? Hosp Pediatr. 2014;4(3):172-180. Keeney GE, Gray MP, Morrison AK. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493-499.

Reviewed by Pediatric Editor Weijen Chang, MD, SFHM, FAAP, associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital.

Clinical question: Does targeting a higher mean arterial pressure (MAP) in patients with septic shock lead to decreased mortality compared with targeting a more typical MAP range?

Background: The ideal blood pressure target for patients with septic shock is not currently known. There is some clinical evidence that patients with chronic arterial hypertension may require higher blood pressure to sustain kidney function.

Study design: Multicenter, randomized, stratified, open-label clinical trial.

Setting: ICUs at 29 centers in France

Synopsis: Researchers randomized 776 patients with septic shock to receive vasopressor treatment to maintain a MAP of 80-85 mmHg (high-target group) or 65-70 mmHg (low-target group). There was no significant difference between groups in the primary outcome of death at 28 days (HR in the high target group 1.07; 95% CI 0.84-1.38; P=0.57).

In patients with chronic arterial hypertension, those who were randomized to the high-target group had a reduced risk of doubling of plasma creatinine or need for renal-replacement therapy from days one to seven. Patients in the high-target group received larger amounts of vasopressors and for a longer period of time. There was no difference between the groups in the overall incidence of serious adverse events, though significantly more patients in the high-target group (6.7%) developed new onset atrial fibrillation compared with those in the low-target group (2.8%).

Bottom line: Mortality at 28 days was not significantly different in patients with septic shock who were randomized to a higher MAP target compared to patients who had a lower MAP target; this lower target encompasses the 65 mmHg target that is listed in the Surviving Sepsis Campaign guidelines.

Citation: Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.

Clinical question: Does targeting a higher mean arterial pressure (MAP) in patients with septic shock lead to decreased mortality compared with targeting a more typical MAP range?

Background: The ideal blood pressure target for patients with septic shock is not currently known. There is some clinical evidence that patients with chronic arterial hypertension may require higher blood pressure to sustain kidney function.

Study design: Multicenter, randomized, stratified, open-label clinical trial.

Setting: ICUs at 29 centers in France

Synopsis: Researchers randomized 776 patients with septic shock to receive vasopressor treatment to maintain a MAP of 80-85 mmHg (high-target group) or 65-70 mmHg (low-target group). There was no significant difference between groups in the primary outcome of death at 28 days (HR in the high target group 1.07; 95% CI 0.84-1.38; P=0.57).

In patients with chronic arterial hypertension, those who were randomized to the high-target group had a reduced risk of doubling of plasma creatinine or need for renal-replacement therapy from days one to seven. Patients in the high-target group received larger amounts of vasopressors and for a longer period of time. There was no difference between the groups in the overall incidence of serious adverse events, though significantly more patients in the high-target group (6.7%) developed new onset atrial fibrillation compared with those in the low-target group (2.8%).

Bottom line: Mortality at 28 days was not significantly different in patients with septic shock who were randomized to a higher MAP target compared to patients who had a lower MAP target; this lower target encompasses the 65 mmHg target that is listed in the Surviving Sepsis Campaign guidelines.

Citation: Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.

Clinical question: Does targeting a higher mean arterial pressure (MAP) in patients with septic shock lead to decreased mortality compared with targeting a more typical MAP range?

Background: The ideal blood pressure target for patients with septic shock is not currently known. There is some clinical evidence that patients with chronic arterial hypertension may require higher blood pressure to sustain kidney function.

Study design: Multicenter, randomized, stratified, open-label clinical trial.

Setting: ICUs at 29 centers in France

Synopsis: Researchers randomized 776 patients with septic shock to receive vasopressor treatment to maintain a MAP of 80-85 mmHg (high-target group) or 65-70 mmHg (low-target group). There was no significant difference between groups in the primary outcome of death at 28 days (HR in the high target group 1.07; 95% CI 0.84-1.38; P=0.57).

In patients with chronic arterial hypertension, those who were randomized to the high-target group had a reduced risk of doubling of plasma creatinine or need for renal-replacement therapy from days one to seven. Patients in the high-target group received larger amounts of vasopressors and for a longer period of time. There was no difference between the groups in the overall incidence of serious adverse events, though significantly more patients in the high-target group (6.7%) developed new onset atrial fibrillation compared with those in the low-target group (2.8%).

Bottom line: Mortality at 28 days was not significantly different in patients with septic shock who were randomized to a higher MAP target compared to patients who had a lower MAP target; this lower target encompasses the 65 mmHg target that is listed in the Surviving Sepsis Campaign guidelines.

Citation: Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.

Clinical question: Do different thresholds for red blood cell (RBC) transfusion influence the risk of infection, and does leukocyte reduction also influence the risk of infection?

Background: RBC transfusion is a common and costly medical intervention performed across U.S. hospitals. Scientists suspect that RBC transfusion may have immunomodulatory properties and may affect a patient’s risk of acquiring various infections.

Study design: Meta-analysis and systematic review.

Setting: International adult, pediatric, obstetric medical and surgical wards, and ICUs.

Synopsis: Eighteen studies performed were included in the meta-analysis of published randomized trials comparing restrictive to liberal RBC transfusion strategies in which infectious outcomes were reported. Patient enrollment spanned from 1994 to 2012. Six of the trials included pediatric patients. For adult patients, the restrictive RBC transfusion threshold ranged from 6.4–9.7 g/dL, while the liberal target ranged from 9-11.3 g/dL in included trials.

The overall pooled risk ratio for the association of restrictive vs. liberal transfusion threshold with infection was 0.99 (95% CI, 0.78-0.99; P=0.033). A decreased risk of infection with the use of a restrictive transfusion compared with a liberal threshold persisted in studies of leukocyte-reduced blood products.

Bottom line: Restrictive RBC transfusion thresholds are associated with a decreased risk of acquiring healthcare-associated infections compared with liberal transfusion thresholds.

Citation: Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: A systematic review and meta-analysis. JAMA. 2014;311(13):1317-1326.

Clinical question: Do different thresholds for red blood cell (RBC) transfusion influence the risk of infection, and does leukocyte reduction also influence the risk of infection?

Background: RBC transfusion is a common and costly medical intervention performed across U.S. hospitals. Scientists suspect that RBC transfusion may have immunomodulatory properties and may affect a patient’s risk of acquiring various infections.

Study design: Meta-analysis and systematic review.

Setting: International adult, pediatric, obstetric medical and surgical wards, and ICUs.

Synopsis: Eighteen studies performed were included in the meta-analysis of published randomized trials comparing restrictive to liberal RBC transfusion strategies in which infectious outcomes were reported. Patient enrollment spanned from 1994 to 2012. Six of the trials included pediatric patients. For adult patients, the restrictive RBC transfusion threshold ranged from 6.4–9.7 g/dL, while the liberal target ranged from 9-11.3 g/dL in included trials.

The overall pooled risk ratio for the association of restrictive vs. liberal transfusion threshold with infection was 0.99 (95% CI, 0.78-0.99; P=0.033). A decreased risk of infection with the use of a restrictive transfusion compared with a liberal threshold persisted in studies of leukocyte-reduced blood products.

Bottom line: Restrictive RBC transfusion thresholds are associated with a decreased risk of acquiring healthcare-associated infections compared with liberal transfusion thresholds.

Citation: Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: A systematic review and meta-analysis. JAMA. 2014;311(13):1317-1326.

Clinical question: Do different thresholds for red blood cell (RBC) transfusion influence the risk of infection, and does leukocyte reduction also influence the risk of infection?

Background: RBC transfusion is a common and costly medical intervention performed across U.S. hospitals. Scientists suspect that RBC transfusion may have immunomodulatory properties and may affect a patient’s risk of acquiring various infections.

Study design: Meta-analysis and systematic review.

Setting: International adult, pediatric, obstetric medical and surgical wards, and ICUs.

Synopsis: Eighteen studies performed were included in the meta-analysis of published randomized trials comparing restrictive to liberal RBC transfusion strategies in which infectious outcomes were reported. Patient enrollment spanned from 1994 to 2012. Six of the trials included pediatric patients. For adult patients, the restrictive RBC transfusion threshold ranged from 6.4–9.7 g/dL, while the liberal target ranged from 9-11.3 g/dL in included trials.

The overall pooled risk ratio for the association of restrictive vs. liberal transfusion threshold with infection was 0.99 (95% CI, 0.78-0.99; P=0.033). A decreased risk of infection with the use of a restrictive transfusion compared with a liberal threshold persisted in studies of leukocyte-reduced blood products.

Bottom line: Restrictive RBC transfusion thresholds are associated with a decreased risk of acquiring healthcare-associated infections compared with liberal transfusion thresholds.

Citation: Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: A systematic review and meta-analysis. JAMA. 2014;311(13):1317-1326.

Clinical question: Are CT scans of the head diagnostically helpful in hospitalized patients with delirium?

Background: Studies have investigated the use of head CT scans for the evaluation of delirium in the ED, but there is scant information about the utility of head CT scans in the assessment of the hospitalized patient with delirium.

Study design: Retrospective medical record review.

Setting: Large academic medical center in Massachusetts.

Synopsis: This study was designed to assess whether head CT scans obtained on patients without a history of head trauma, fall, known intracranial process, or new neurologic deficit were useful in the workup of delirium. During a two-year period, 1,714 CT scans of the head were performed, and 398 listed the indication for the scan as “delirium, altered mental status, confusion, encephalopathy, somnolence, or unresponsiveness.” Patients with the risk factors of trauma, fall, new neurologic deficit, and known intracranial process were excluded, and 220 patients’ records were reviewed.

Only six head CT scans (2.7%) revealed an acute intracranial process. Many chronic findings were noted, such as atrophy, small vessel ischemic disease, and old stroke. The authors found that the diagnostic utility was low for a head CT scan in a patient with delirium but noted no risk factors. There may be a subset of patients in whom the diagnostic yield is higher, such as those on anticoagulation or more obtunded patients.

Bottom line: In delirious inpatients without a history of head trauma, fall, known intracranial process, or new neurologic deficit, head CT scan has low diagnostic utility.

Citation: Theisen-Toupal J, Breu AC, Mattison ML, Arnaout R. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium [published online ahead of print April 15, 2014]. J Hosp Med.

Clinical question: Are CT scans of the head diagnostically helpful in hospitalized patients with delirium?

Background: Studies have investigated the use of head CT scans for the evaluation of delirium in the ED, but there is scant information about the utility of head CT scans in the assessment of the hospitalized patient with delirium.

Study design: Retrospective medical record review.

Setting: Large academic medical center in Massachusetts.

Synopsis: This study was designed to assess whether head CT scans obtained on patients without a history of head trauma, fall, known intracranial process, or new neurologic deficit were useful in the workup of delirium. During a two-year period, 1,714 CT scans of the head were performed, and 398 listed the indication for the scan as “delirium, altered mental status, confusion, encephalopathy, somnolence, or unresponsiveness.” Patients with the risk factors of trauma, fall, new neurologic deficit, and known intracranial process were excluded, and 220 patients’ records were reviewed.

Only six head CT scans (2.7%) revealed an acute intracranial process. Many chronic findings were noted, such as atrophy, small vessel ischemic disease, and old stroke. The authors found that the diagnostic utility was low for a head CT scan in a patient with delirium but noted no risk factors. There may be a subset of patients in whom the diagnostic yield is higher, such as those on anticoagulation or more obtunded patients.

Bottom line: In delirious inpatients without a history of head trauma, fall, known intracranial process, or new neurologic deficit, head CT scan has low diagnostic utility.

Citation: Theisen-Toupal J, Breu AC, Mattison ML, Arnaout R. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium [published online ahead of print April 15, 2014]. J Hosp Med.

Clinical question: Are CT scans of the head diagnostically helpful in hospitalized patients with delirium?

Background: Studies have investigated the use of head CT scans for the evaluation of delirium in the ED, but there is scant information about the utility of head CT scans in the assessment of the hospitalized patient with delirium.

Study design: Retrospective medical record review.

Setting: Large academic medical center in Massachusetts.

Synopsis: This study was designed to assess whether head CT scans obtained on patients without a history of head trauma, fall, known intracranial process, or new neurologic deficit were useful in the workup of delirium. During a two-year period, 1,714 CT scans of the head were performed, and 398 listed the indication for the scan as “delirium, altered mental status, confusion, encephalopathy, somnolence, or unresponsiveness.” Patients with the risk factors of trauma, fall, new neurologic deficit, and known intracranial process were excluded, and 220 patients’ records were reviewed.

Only six head CT scans (2.7%) revealed an acute intracranial process. Many chronic findings were noted, such as atrophy, small vessel ischemic disease, and old stroke. The authors found that the diagnostic utility was low for a head CT scan in a patient with delirium but noted no risk factors. There may be a subset of patients in whom the diagnostic yield is higher, such as those on anticoagulation or more obtunded patients.

Bottom line: In delirious inpatients without a history of head trauma, fall, known intracranial process, or new neurologic deficit, head CT scan has low diagnostic utility.

Citation: Theisen-Toupal J, Breu AC, Mattison ML, Arnaout R. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium [published online ahead of print April 15, 2014]. J Hosp Med.

Clinical question: Does an increased hospitalist workload lead to increased costs, longer lengths of stay, and worse medical outcomes?

Background: There is evidence that increased resident physician workloads contribute to adverse medical outcomes, but this has not been assessed in the hospital medicine setting. In a recent national survey of hospitalists, almost half reported that they had managed workloads that felt “unsafe.”

Study design: Retrospective cohort study.

Setting: Academic community health system in Delaware.

Synopsis: This study examined the effect of hospital occupancy and hospitalist workloads, using both daily relative value units (RVUs) and hospitalists’ daily patient census, on length of stay (LOS), hospital costs, inpatient mortality, activation of rapid response system (a proxy measure for decompensation), and 30-day readmission rates. Authors reviewed 20,241 hospitalizations and found that when hospitalist daily censuses exceeded 15 patients (or RVU of 25), length of stay increased “exponentially.” Increased workloads were not associated with worsening medical outcomes or diminished patient satisfaction scores.

The authors caution that the significantly increased costs and LOS at higher patient censuses raise concerns that hospital policies that incentivize productivity may “undermine larger system efforts targeting efficiency and costs of care.” They also suggest that hospitalist groups’ staffing approaches need to accommodate fluctuations in hospital occupancy.

Bottom line: When a hospitalist’s workload exceeds a census of 15 patients, the length of stay and cost may increase dramatically.

Article Reference: Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med. 2014;174(5):786-793.

Clinical question: Does an increased hospitalist workload lead to increased costs, longer lengths of stay, and worse medical outcomes?

Background: There is evidence that increased resident physician workloads contribute to adverse medical outcomes, but this has not been assessed in the hospital medicine setting. In a recent national survey of hospitalists, almost half reported that they had managed workloads that felt “unsafe.”

Study design: Retrospective cohort study.

Setting: Academic community health system in Delaware.

Synopsis: This study examined the effect of hospital occupancy and hospitalist workloads, using both daily relative value units (RVUs) and hospitalists’ daily patient census, on length of stay (LOS), hospital costs, inpatient mortality, activation of rapid response system (a proxy measure for decompensation), and 30-day readmission rates. Authors reviewed 20,241 hospitalizations and found that when hospitalist daily censuses exceeded 15 patients (or RVU of 25), length of stay increased “exponentially.” Increased workloads were not associated with worsening medical outcomes or diminished patient satisfaction scores.

The authors caution that the significantly increased costs and LOS at higher patient censuses raise concerns that hospital policies that incentivize productivity may “undermine larger system efforts targeting efficiency and costs of care.” They also suggest that hospitalist groups’ staffing approaches need to accommodate fluctuations in hospital occupancy.

Bottom line: When a hospitalist’s workload exceeds a census of 15 patients, the length of stay and cost may increase dramatically.

Article Reference: Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med. 2014;174(5):786-793.

Clinical question: Does an increased hospitalist workload lead to increased costs, longer lengths of stay, and worse medical outcomes?

Background: There is evidence that increased resident physician workloads contribute to adverse medical outcomes, but this has not been assessed in the hospital medicine setting. In a recent national survey of hospitalists, almost half reported that they had managed workloads that felt “unsafe.”

Study design: Retrospective cohort study.

Setting: Academic community health system in Delaware.

Synopsis: This study examined the effect of hospital occupancy and hospitalist workloads, using both daily relative value units (RVUs) and hospitalists’ daily patient census, on length of stay (LOS), hospital costs, inpatient mortality, activation of rapid response system (a proxy measure for decompensation), and 30-day readmission rates. Authors reviewed 20,241 hospitalizations and found that when hospitalist daily censuses exceeded 15 patients (or RVU of 25), length of stay increased “exponentially.” Increased workloads were not associated with worsening medical outcomes or diminished patient satisfaction scores.

The authors caution that the significantly increased costs and LOS at higher patient censuses raise concerns that hospital policies that incentivize productivity may “undermine larger system efforts targeting efficiency and costs of care.” They also suggest that hospitalist groups’ staffing approaches need to accommodate fluctuations in hospital occupancy.

Bottom line: When a hospitalist’s workload exceeds a census of 15 patients, the length of stay and cost may increase dramatically.

Article Reference: Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med. 2014;174(5):786-793.

Clinical question: In patients at risk for vascular complications undergoing noncardiac surgery, do the benefits of aspirin outweigh the risks?

Background: Aspirin has been shown to reduce the rate of myocardial infarction (MI) and major vascular events in patients not undergoing surgery. The benefits of initiating or continuing aspirin in patients undergoing surgery, balanced by the potential increase in bleeding risk, have not been widely studied.

Study design: International randomized placebo-controlled trial with a 2-by-2 factorial design.

Setting: One hundred thirty-five hospitals in 23 countries, from 2010-2013.

Synopsis: The study enrolled 10,010 patients, with a mean age of 68.6 years. Inclusion criteria were age >45 years old and risk for vascular complications, defined as a history of coronary artery disease, peripheral vascular disease, or cerebrovascular accident; major vascular surgery; or at least three of the following: age >70, congestive heart failure, transient ischemic attack, hypertension, diabetes mellitus type 2, creatinine >2 mg/dL, recent smoking, undergoing major surgery, or urgent/emergent surgery.

Groups were stratified by current use of aspirin and then assigned to aspirin or placebo; patients on aspirin held it a median of seven days before surgery. Those in the active group received 200 mg of aspirin pre-operatively. Patients not previously on aspirin then continued aspirin at 100 mg/day for 30 days; those on aspirin previously received 100 mg/day for seven days and then resumed their prior dose.

No difference was found in the primary outcome of death or non-fatal MI at 30 days, but aspirin was noted to increase the risk of major bleeding (4.6% vs. 3.8%, P=0.04), most commonly occurring at the surgical site (78.3%) and the GI tract (9.3%). Because major bleeding can be associated with peri-operative MI, this may have counteracted the cardiovascular benefits of aspirin.

Bottom line: Peri-operative administration of aspirin to patients at risk for vascular complications undergoing noncardiac surgery does not decrease the risk of peri-operative death or MI and may increase the risk of post-operative bleeding.

Citation: Devereaux PJ, Mrkobrada M, Sessler DI, et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494-1503.

Clinical question: In patients at risk for vascular complications undergoing noncardiac surgery, do the benefits of aspirin outweigh the risks?

Background: Aspirin has been shown to reduce the rate of myocardial infarction (MI) and major vascular events in patients not undergoing surgery. The benefits of initiating or continuing aspirin in patients undergoing surgery, balanced by the potential increase in bleeding risk, have not been widely studied.

Study design: International randomized placebo-controlled trial with a 2-by-2 factorial design.

Setting: One hundred thirty-five hospitals in 23 countries, from 2010-2013.

Synopsis: The study enrolled 10,010 patients, with a mean age of 68.6 years. Inclusion criteria were age >45 years old and risk for vascular complications, defined as a history of coronary artery disease, peripheral vascular disease, or cerebrovascular accident; major vascular surgery; or at least three of the following: age >70, congestive heart failure, transient ischemic attack, hypertension, diabetes mellitus type 2, creatinine >2 mg/dL, recent smoking, undergoing major surgery, or urgent/emergent surgery.

Groups were stratified by current use of aspirin and then assigned to aspirin or placebo; patients on aspirin held it a median of seven days before surgery. Those in the active group received 200 mg of aspirin pre-operatively. Patients not previously on aspirin then continued aspirin at 100 mg/day for 30 days; those on aspirin previously received 100 mg/day for seven days and then resumed their prior dose.

No difference was found in the primary outcome of death or non-fatal MI at 30 days, but aspirin was noted to increase the risk of major bleeding (4.6% vs. 3.8%, P=0.04), most commonly occurring at the surgical site (78.3%) and the GI tract (9.3%). Because major bleeding can be associated with peri-operative MI, this may have counteracted the cardiovascular benefits of aspirin.

Bottom line: Peri-operative administration of aspirin to patients at risk for vascular complications undergoing noncardiac surgery does not decrease the risk of peri-operative death or MI and may increase the risk of post-operative bleeding.

Citation: Devereaux PJ, Mrkobrada M, Sessler DI, et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494-1503.

Clinical question: In patients at risk for vascular complications undergoing noncardiac surgery, do the benefits of aspirin outweigh the risks?

Background: Aspirin has been shown to reduce the rate of myocardial infarction (MI) and major vascular events in patients not undergoing surgery. The benefits of initiating or continuing aspirin in patients undergoing surgery, balanced by the potential increase in bleeding risk, have not been widely studied.

Study design: International randomized placebo-controlled trial with a 2-by-2 factorial design.

Setting: One hundred thirty-five hospitals in 23 countries, from 2010-2013.

Synopsis: The study enrolled 10,010 patients, with a mean age of 68.6 years. Inclusion criteria were age >45 years old and risk for vascular complications, defined as a history of coronary artery disease, peripheral vascular disease, or cerebrovascular accident; major vascular surgery; or at least three of the following: age >70, congestive heart failure, transient ischemic attack, hypertension, diabetes mellitus type 2, creatinine >2 mg/dL, recent smoking, undergoing major surgery, or urgent/emergent surgery.

Groups were stratified by current use of aspirin and then assigned to aspirin or placebo; patients on aspirin held it a median of seven days before surgery. Those in the active group received 200 mg of aspirin pre-operatively. Patients not previously on aspirin then continued aspirin at 100 mg/day for 30 days; those on aspirin previously received 100 mg/day for seven days and then resumed their prior dose.

No difference was found in the primary outcome of death or non-fatal MI at 30 days, but aspirin was noted to increase the risk of major bleeding (4.6% vs. 3.8%, P=0.04), most commonly occurring at the surgical site (78.3%) and the GI tract (9.3%). Because major bleeding can be associated with peri-operative MI, this may have counteracted the cardiovascular benefits of aspirin.

Bottom line: Peri-operative administration of aspirin to patients at risk for vascular complications undergoing noncardiac surgery does not decrease the risk of peri-operative death or MI and may increase the risk of post-operative bleeding.

Citation: Devereaux PJ, Mrkobrada M, Sessler DI, et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494-1503.

Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?

Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy-six sites in 13 countries.

Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.

The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.

Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.

Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.

Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?

Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy-six sites in 13 countries.

Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.

The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.

Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.

Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.

Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?

Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy-six sites in 13 countries.

Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.

The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.

Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.

Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.

Clinical question: What new recommendations are made in the AHA/ACC/HRS atrial fibrillation guidelines?

Background: This is the AHA’s first comprehensive update on atrial fibrillation since 2006; there were two intervening focused updates in 2011.

Synopsis: The majority of the new recommendations center on patient selection for anticoagulation and the role of the new oral anticoagulants.

CHA2DS2-VASc is now recommended over CHADS2 for evaluation of stroke risk, with anticoagulation recommended for a score of two or greater, or for a patient with any prior history of stroke or transient ischemic attack.

Warfarin, direct thrombin inhibitors, or factor Xa inhibitors may be considered in patients with normal renal function. Reduced doses of these medications may be considered in patients with moderate to severe renal dysfunction but have not been studied in clinical trials.

Warfarin remains the drug of choice for patients on hemodialysis and those with hemodynamically significant mitral stenosis or aortic valve replacement.

The clinical utility of bleeding risk scores remains insufficient for formal recommendations. There is sparse evidence on which to base recommendations for bridging, but additional studies, such as the BRIDGE trial, are ongoing. A liberal rate control strategy targeting heart rates <110 in asymptomatic patients with preserved systolic function is reasonable; ideal rate control targets remain controversial.

Citation: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online ahead of print April 10, 2014]. Circulation.

Clinical question: What new recommendations are made in the AHA/ACC/HRS atrial fibrillation guidelines?

Background: This is the AHA’s first comprehensive update on atrial fibrillation since 2006; there were two intervening focused updates in 2011.

Synopsis: The majority of the new recommendations center on patient selection for anticoagulation and the role of the new oral anticoagulants.

CHA2DS2-VASc is now recommended over CHADS2 for evaluation of stroke risk, with anticoagulation recommended for a score of two or greater, or for a patient with any prior history of stroke or transient ischemic attack.

Warfarin, direct thrombin inhibitors, or factor Xa inhibitors may be considered in patients with normal renal function. Reduced doses of these medications may be considered in patients with moderate to severe renal dysfunction but have not been studied in clinical trials.

Warfarin remains the drug of choice for patients on hemodialysis and those with hemodynamically significant mitral stenosis or aortic valve replacement.

The clinical utility of bleeding risk scores remains insufficient for formal recommendations. There is sparse evidence on which to base recommendations for bridging, but additional studies, such as the BRIDGE trial, are ongoing. A liberal rate control strategy targeting heart rates <110 in asymptomatic patients with preserved systolic function is reasonable; ideal rate control targets remain controversial.

Citation: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online ahead of print April 10, 2014]. Circulation.

Clinical question: What new recommendations are made in the AHA/ACC/HRS atrial fibrillation guidelines?

Background: This is the AHA’s first comprehensive update on atrial fibrillation since 2006; there were two intervening focused updates in 2011.

Synopsis: The majority of the new recommendations center on patient selection for anticoagulation and the role of the new oral anticoagulants.

CHA2DS2-VASc is now recommended over CHADS2 for evaluation of stroke risk, with anticoagulation recommended for a score of two or greater, or for a patient with any prior history of stroke or transient ischemic attack.

Warfarin, direct thrombin inhibitors, or factor Xa inhibitors may be considered in patients with normal renal function. Reduced doses of these medications may be considered in patients with moderate to severe renal dysfunction but have not been studied in clinical trials.

Warfarin remains the drug of choice for patients on hemodialysis and those with hemodynamically significant mitral stenosis or aortic valve replacement.

The clinical utility of bleeding risk scores remains insufficient for formal recommendations. There is sparse evidence on which to base recommendations for bridging, but additional studies, such as the BRIDGE trial, are ongoing. A liberal rate control strategy targeting heart rates <110 in asymptomatic patients with preserved systolic function is reasonable; ideal rate control targets remain controversial.

Citation: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online ahead of print April 10, 2014]. Circulation.