Article: TME200221
Date: October 23, 2013
Time: 23:1
Advanced Emergency Nursing Journal Vol. 35, No. 4, pp. 283–286 C 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright
R E S E A R C H
T O
Practice Column Editors: Patricia Kunz Howard, PhD, RN, CEN, CPEN, NE-BC, FAEN, FAAN, and Susan E. Shapiro, PhD, RN, FAAN
Complications Associated With Oral Anticoagulation Therapy Patricia Kunz Howard, PhD, RN, CEN, CPEN, NE-BC, FAEN, FAAN
Abstract Review of recent evidence with translation to practice for the advanced practice nurse (APN) role is presented using a case study module for “Complications Associated With Oral Anticoagulation Therapy.” The study results showed that bleeding complications were most often due to gastrointestinal bleeding associated with anticoagulants (dabigatran 80% and warfarin 48%). The implications and clinical relevance of these findings for APNs are discussed highlighting best evidence. Key words: anticoagulant, bleeding, complications
T
HE PURPOSE of this column is to assist advanced practice nurses (APNs) with the translation of research to practice. For this column in each issue, a topic and a particular research study are selected. The stage is set by introducing the importance of the topic using a case-based scenario. The research article is then reviewed and critiqued, and finally, the implications for translation into practice are discussed. In this column, the following research article is reviewed: “Hemorrhagic Complications in Emergency Department Patients Who Are Receiving Dabigatran Compared With Warfarin” (Berger, Salhanick, Chase, & Ganetsky, 2013). The
implications of these findings for APNs are discussed.
THE CASE A 54-year-old Caucasian man (B.R.) presented to the emergency department (ED) complaining of an irregular heart beat and fatigue for the past week, without other associated symptoms. When placed on a cardiac monitor, he was noted to be in atrial fibrillation with a heart rate of 90–110 beats/min; respiratory rate of 18/min and nonlabored; afebrile; blood pressure of 134/76 mmHg; and oxygen saturation of 99% on room air. Further questioning revealed that he had a physical examination 6 months ago with a normal electrocardiogram (ECG); he denied chronic illness or taking any routine medications, including over-the-counter medications or supplements. He stated that he was healthy, exercised routinely, and did not use tobacco products, alcohol, or other substances. He
Author Affiliation: Emergency Services, University of Kentucky Chandler Medical Center, Lexington. Disclosure: The author reports no conflicts of interest. Corresponding Author: Patricia Kunz Howard, PhD, RN, CEN, CPEN, NE-BC, FAEN, FAAN, Emergency Services, University of Kentucky Chandler Medical Center, Lexington, KY 40536 ([email protected]). DOI: 10.1097/TME.0b013e3182a9e9a2
283
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Article: TME200221
Date: October 23, 2013
Time: 23:1
Advanced Emergency Nursing Journal
284
noted that his father had had an irregular heartbeat and took medication for it. Physical examination revealed normal heart sounds, 2+ palpable pulses in all extremities, no edema, and no complaints of shortness of breath; the remainder of the exam was unremarkable. As the APN caring for this patient, the clinician explained that he would need additional diagnostic testing, medication therapy, and teaching prior to discharge. The patient was concerned about missing work and wanted to know how soon he could leave the ED. The clinician explained to the patient the risks of thromboembolic-related phenomena associated with atrial fibrillation and the need for outpatient anticoagulation therapy.
DESIGN AND METHODS The purpose of this study (Berger et al. 2013) was to compare bleeding complications associated with dabigatran and warfarin in a sample of patients with a diagnosis of anticoagulant-related bleeding complications admitted through the ED. Using a prospective medical record review of eligible patients, the authors abstracted data on the basis of agreeupon definitions of all variables, for example, “major” and “life-threatening” hemorrhages were differentiated on the basis of reduction in hemoglobin measurements and the number of units of blood transfused over a period of time, and they performed a blind review of
a sample of their records to ensure interrater reliability. The investigators provide only the briefest of descriptions of their data analysis, stating, “Descriptive statistics were used and 95% confidence intervals were calculated.” They do not elaborate any further.
RESULTS AND DISCUSSION A total of 138 patients met inclusion criteria, 15 were receiving dabigatran and 123 were receiving warfarin. Because of the vastly unequal sample sizes, the authors randomly selected 20% of days in the study and identified 25 patients admitted on those days who met inclusion criteria and were receiving warfarin, giving them an analytic sample size of 40 (15 patients receiving dabigatran and 25 receiving warfarin). See Table 1 for the selected findings reported by Berg et al. (2013). As can be seen, although 12 patients in each group experienced gastrointestinal (GI) bleeding, this represented a far greater percentage of the dabigatran group than the warfarin group. No patient receiving dabigatran experienced intracranial (IC) hemorrhage, but eight patients (32%) in the warfarin group did, although only three of the eight experienced spontaneous IC bleeds; the other five experienced head trauma. Dabigatran-taking patients showed a higher percentage of acute kidney injuries, and warfarin-taking patients had higher percentages of both major and
Table 1. Selected results from Berger et al. (2013)
Findings GI bleeding IC bleeding Major bleeding Life-threatening bleeding Acute kidney injury Deaths
Patients Receiving Dabigatran (N = 15,100%)
Patients Receiving Warfarin (N = 25,100%)
12 (80%) 0 (0%) 9 (60%) 4 (27%) 8 (53%) 2 (13%)
12 (48%) 8 (32%) 19 (76%) 14 (56%) 10 (42%) 3 (12%)
Note. GI = gastrointestinal; IC = intracranial.
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Article: TME200221
October–December 2013
r Vol. 35, No. 4
Date: October 23, 2013
Time: 23:1
Complications Associated With Oral Anticoagulation Therapy
life-threatening bleeding complications. Both groups had similar percentages of deaths. The average length of stay for the dabigatran group and the warfarin group was 3.5 and 6 days, respectively. It is critical to note that for all the findings reported, there were very wide 95% confidence intervals, indicating a wide variability in both relatively small samples. The authors concluded that although there were fatalities in both groups, overall, the patients who received dabigatran had a less complicated hospital course than those who received warfarin. No change in clinical management has been recommended as an outcome of their findings, but the investigators do suggest monitoring patients’ renal function while receiving dabigatran. The investigators acknowledged that their conclusions may be limited by the fact that they were unable to determine which agent might create a higher risk of bleeding complications because their data did not measure bleeding rates between agents. The authors also identified that the warfarin group included patients with IC bleeding secondary to trauma (five of the eight occurrences of IC bleeding), which is a recognized risk of anticoagulation therapy. Sampling bias could also be a limitation of this study because subjects could have been missed if the bleeding complication was not their primary admitting diagnosis (Berger et al., 2013). PATTI’S PERSPECTIVE The investigators found evidence of different bleeding complications associated with both common anticoagulation therapies. The methods and sampling are challenging to evaluate because of the limited information provided in the article. The authors did provide some detail about the rigor of their data abstraction process, including their method to test for concordance between raters (found to be quite acceptable at 96%). The sampling method for the warfarin group while appearing to result in a random sample may not have been statistically valid, although this method of coming up with similar sample sizes may
285
have been the only option at the time of the study. Finally, even though the authors listed several important limitations in their study, they failed to emphasize the fact that their very small sample sizes and resulting wide confidence intervals severely limit the generalizability of the findings. That said, the article of Berger et al. (2013) provides APNs with useful information about risks and benefits associated with the use of dabigatran versus warfarin, and the findings are very similar to those reported previously (RE-LY, Connolly et al., 2009). In addition, it provides evidence for concern related to GI bleeding complications when dabigatran is administered. In their discussion, Berger et al. (2013) presented supporting rationale for risk factors of dabigatran-induced bleeding that included advanced age, known renal disease, and higher doses of dabigatran. As clinical use of dabigatran increases, it will be important to have additional studies to validate the pattern of increased GI bleeding complications found in the study of Berger et al. (2013). It is of interest to note that the package insert does warn against the use of dabigatran if a history of GI bleeding exists (Boehringer Ingelheim, 2013). Other pertinent information for APNs to include when educating their patients are potential drug-to-drug interactions when using dabigatran, including avoiding rifampin as the effectiveness of the dabigatran is reduced, and the use of agents that inhibit platelet function should be avoided, as with other anticoagulants. One of the advantages of prescribing dabigatran is that, unlike warfarin, there are no dietary restrictions with its use. This study provides APNs with information that can be helpful when planning care for patients with new-onset atrial fibrillation. Understanding the inherent risks related to bleeding complications is important both as a prescriber of the medication and for patient teaching. Decisions about drug choice may be influenced by mechanisms of action of the drug; dabigatran is a direct thrombin inhibitor compared with warfarin, which acts as a vitamin K antagonist. One study (Connolly et al.,
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Article: TME200221
Date: October 23, 2013
Advanced Emergency Nursing Journal
286
2009) has shown dabigatran to be 35% more effective than warfarin in preventing stroke in patients with atrial fibrillation not related to heart valve replacement (dabigatran is not indicated for patients with prosthetic heart valves and atrial fibrillation; Boehringer Ingelheim, 2013). Patients should receive information on signs of bleeding complications for either agent, but a special emphasis should be placed on signs of GI bleeding if dabigatran is the agent chosen. Other findings of interest to APNs include the potential for increased bleeding complications in the presence of acute kidney injury. Patients with known renal insufficiency may not be ideal candidates for dabigatran because there is a significantly increased serum concentration of dabigatran in the setting of renal disease compared with serum concentrations of dabigatran with normal renal function (Beasley, Unger, & Temple, 2011). Advanced practice nurses may consider obtaining a comprehensive serum metabolic profile before prescribing dabigatran as outpatient anticoagulation therapy for patients with atrial fibrillation to establish baseline renal function. Managing patients requiring outpatient anticoagulation therapy can present challenges for APNs, especially in the ED when there may only be a single encounter with patients. Dabigatran is a less complicated option for use with patients seen episodically because, unlike warfarin, routine monitoring of the coagulation status of patients is not needed. Providing patients with detailed information about the need for compliance with the prescribed pharmacological regimen is important, and it is critically important that patients understand when to seek care for potential complications such as GI bleeding.
Time: 23:1
CASE STUDY OUTCOME After a review of baseline diagnostic testing that included troponin, coagulation studies, and comprehensive metabolic profile that were all within normal limits, the APN discussed with B.R. the risks and benefits of dabigatran versus warfarin. The patient and the APN agreed that with his prior good health and current job-related travel requirements, dabigatran was the best first-line management strategy for preventing thromboembolic complications associated with his atrial fibrillation. The APN concurred that dabigatran was the safer choice, given the potential difficulty B.R. would have had with consistent monitoring of warfarin. The patient was able to verbalize an understanding of bleeding complications to watch for and when to seek additional treatment of potential complications. B.R. also verbalized an understanding of the need for follow-up to establish care for monitoring of the atrial fibrillation and potential complications. REFERENCES Beasley, B. N., Unger, E. F., & Temple, R. (2011). Anticoagulant options—Why the FDA approved a higher but not a lower dose of dabigatran. The New England Journal of Medicine, 364, 1788–1790. Berger, R. M., Salhanick, S. D., Chase, M., & Ganetsky, M. (2013). Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Annals of Emergency Medicine, 61, 475–479. Boehringer Ingelheim. (2013). PRADXA highlights of prescribing information. Retrieved from https:// www.pradaxa.com/about-pradaxa.jsp Connolly, S. J., Ezekowitz, M. D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., . . . Wallentin, L. (2009). Dabigatran versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine, 361, 1139–1151.
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Date: October 23, 2013
Time: 23:1
Advanced Emergency Nursing Journal Vol. 35, No. 4, pp. 283–286 C 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright
R E S E A R C H
T O
Practice Column Editors: Patricia Kunz Howard, PhD, RN, CEN, CPEN, NE-BC, FAEN, FAAN, and Susan E. Shapiro, PhD, RN, FAAN
Complications Associated With Oral Anticoagulation Therapy Patricia Kunz Howard, PhD, RN, CEN, CPEN, NE-BC, FAEN, FAAN
Abstract Review of recent evidence with translation to practice for the advanced practice nurse (APN) role is presented using a case study module for “Complications Associated With Oral Anticoagulation Therapy.” The study results showed that bleeding complications were most often due to gastrointestinal bleeding associated with anticoagulants (dabigatran 80% and warfarin 48%). The implications and clinical relevance of these findings for APNs are discussed highlighting best evidence. Key words: anticoagulant, bleeding, complications
T
HE PURPOSE of this column is to assist advanced practice nurses (APNs) with the translation of research to practice. For this column in each issue, a topic and a particular research study are selected. The stage is set by introducing the importance of the topic using a case-based scenario. The research article is then reviewed and critiqued, and finally, the implications for translation into practice are discussed. In this column, the following research article is reviewed: “Hemorrhagic Complications in Emergency Department Patients Who Are Receiving Dabigatran Compared With Warfarin” (Berger, Salhanick, Chase, & Ganetsky, 2013). The
implications of these findings for APNs are discussed.
THE CASE A 54-year-old Caucasian man (B.R.) presented to the emergency department (ED) complaining of an irregular heart beat and fatigue for the past week, without other associated symptoms. When placed on a cardiac monitor, he was noted to be in atrial fibrillation with a heart rate of 90–110 beats/min; respiratory rate of 18/min and nonlabored; afebrile; blood pressure of 134/76 mmHg; and oxygen saturation of 99% on room air. Further questioning revealed that he had a physical examination 6 months ago with a normal electrocardiogram (ECG); he denied chronic illness or taking any routine medications, including over-the-counter medications or supplements. He stated that he was healthy, exercised routinely, and did not use tobacco products, alcohol, or other substances. He
Author Affiliation: Emergency Services, University of Kentucky Chandler Medical Center, Lexington. Disclosure: The author reports no conflicts of interest. Corresponding Author: Patricia Kunz Howard, PhD, RN, CEN, CPEN, NE-BC, FAEN, FAAN, Emergency Services, University of Kentucky Chandler Medical Center, Lexington, KY 40536 ([email protected]). DOI: 10.1097/TME.0b013e3182a9e9a2
283
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Article: TME200221
Date: October 23, 2013
Time: 23:1
Advanced Emergency Nursing Journal
284
noted that his father had had an irregular heartbeat and took medication for it. Physical examination revealed normal heart sounds, 2+ palpable pulses in all extremities, no edema, and no complaints of shortness of breath; the remainder of the exam was unremarkable. As the APN caring for this patient, the clinician explained that he would need additional diagnostic testing, medication therapy, and teaching prior to discharge. The patient was concerned about missing work and wanted to know how soon he could leave the ED. The clinician explained to the patient the risks of thromboembolic-related phenomena associated with atrial fibrillation and the need for outpatient anticoagulation therapy.
DESIGN AND METHODS The purpose of this study (Berger et al. 2013) was to compare bleeding complications associated with dabigatran and warfarin in a sample of patients with a diagnosis of anticoagulant-related bleeding complications admitted through the ED. Using a prospective medical record review of eligible patients, the authors abstracted data on the basis of agreeupon definitions of all variables, for example, “major” and “life-threatening” hemorrhages were differentiated on the basis of reduction in hemoglobin measurements and the number of units of blood transfused over a period of time, and they performed a blind review of
a sample of their records to ensure interrater reliability. The investigators provide only the briefest of descriptions of their data analysis, stating, “Descriptive statistics were used and 95% confidence intervals were calculated.” They do not elaborate any further.
RESULTS AND DISCUSSION A total of 138 patients met inclusion criteria, 15 were receiving dabigatran and 123 were receiving warfarin. Because of the vastly unequal sample sizes, the authors randomly selected 20% of days in the study and identified 25 patients admitted on those days who met inclusion criteria and were receiving warfarin, giving them an analytic sample size of 40 (15 patients receiving dabigatran and 25 receiving warfarin). See Table 1 for the selected findings reported by Berg et al. (2013). As can be seen, although 12 patients in each group experienced gastrointestinal (GI) bleeding, this represented a far greater percentage of the dabigatran group than the warfarin group. No patient receiving dabigatran experienced intracranial (IC) hemorrhage, but eight patients (32%) in the warfarin group did, although only three of the eight experienced spontaneous IC bleeds; the other five experienced head trauma. Dabigatran-taking patients showed a higher percentage of acute kidney injuries, and warfarin-taking patients had higher percentages of both major and
Table 1. Selected results from Berger et al. (2013)
Findings GI bleeding IC bleeding Major bleeding Life-threatening bleeding Acute kidney injury Deaths
Patients Receiving Dabigatran (N = 15,100%)
Patients Receiving Warfarin (N = 25,100%)
12 (80%) 0 (0%) 9 (60%) 4 (27%) 8 (53%) 2 (13%)
12 (48%) 8 (32%) 19 (76%) 14 (56%) 10 (42%) 3 (12%)
Note. GI = gastrointestinal; IC = intracranial.
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Article: TME200221
October–December 2013
r Vol. 35, No. 4
Date: October 23, 2013
Time: 23:1
Complications Associated With Oral Anticoagulation Therapy
life-threatening bleeding complications. Both groups had similar percentages of deaths. The average length of stay for the dabigatran group and the warfarin group was 3.5 and 6 days, respectively. It is critical to note that for all the findings reported, there were very wide 95% confidence intervals, indicating a wide variability in both relatively small samples. The authors concluded that although there were fatalities in both groups, overall, the patients who received dabigatran had a less complicated hospital course than those who received warfarin. No change in clinical management has been recommended as an outcome of their findings, but the investigators do suggest monitoring patients’ renal function while receiving dabigatran. The investigators acknowledged that their conclusions may be limited by the fact that they were unable to determine which agent might create a higher risk of bleeding complications because their data did not measure bleeding rates between agents. The authors also identified that the warfarin group included patients with IC bleeding secondary to trauma (five of the eight occurrences of IC bleeding), which is a recognized risk of anticoagulation therapy. Sampling bias could also be a limitation of this study because subjects could have been missed if the bleeding complication was not their primary admitting diagnosis (Berger et al., 2013). PATTI’S PERSPECTIVE The investigators found evidence of different bleeding complications associated with both common anticoagulation therapies. The methods and sampling are challenging to evaluate because of the limited information provided in the article. The authors did provide some detail about the rigor of their data abstraction process, including their method to test for concordance between raters (found to be quite acceptable at 96%). The sampling method for the warfarin group while appearing to result in a random sample may not have been statistically valid, although this method of coming up with similar sample sizes may
285
have been the only option at the time of the study. Finally, even though the authors listed several important limitations in their study, they failed to emphasize the fact that their very small sample sizes and resulting wide confidence intervals severely limit the generalizability of the findings. That said, the article of Berger et al. (2013) provides APNs with useful information about risks and benefits associated with the use of dabigatran versus warfarin, and the findings are very similar to those reported previously (RE-LY, Connolly et al., 2009). In addition, it provides evidence for concern related to GI bleeding complications when dabigatran is administered. In their discussion, Berger et al. (2013) presented supporting rationale for risk factors of dabigatran-induced bleeding that included advanced age, known renal disease, and higher doses of dabigatran. As clinical use of dabigatran increases, it will be important to have additional studies to validate the pattern of increased GI bleeding complications found in the study of Berger et al. (2013). It is of interest to note that the package insert does warn against the use of dabigatran if a history of GI bleeding exists (Boehringer Ingelheim, 2013). Other pertinent information for APNs to include when educating their patients are potential drug-to-drug interactions when using dabigatran, including avoiding rifampin as the effectiveness of the dabigatran is reduced, and the use of agents that inhibit platelet function should be avoided, as with other anticoagulants. One of the advantages of prescribing dabigatran is that, unlike warfarin, there are no dietary restrictions with its use. This study provides APNs with information that can be helpful when planning care for patients with new-onset atrial fibrillation. Understanding the inherent risks related to bleeding complications is important both as a prescriber of the medication and for patient teaching. Decisions about drug choice may be influenced by mechanisms of action of the drug; dabigatran is a direct thrombin inhibitor compared with warfarin, which acts as a vitamin K antagonist. One study (Connolly et al.,
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Article: TME200221
Date: October 23, 2013
Advanced Emergency Nursing Journal
286
2009) has shown dabigatran to be 35% more effective than warfarin in preventing stroke in patients with atrial fibrillation not related to heart valve replacement (dabigatran is not indicated for patients with prosthetic heart valves and atrial fibrillation; Boehringer Ingelheim, 2013). Patients should receive information on signs of bleeding complications for either agent, but a special emphasis should be placed on signs of GI bleeding if dabigatran is the agent chosen. Other findings of interest to APNs include the potential for increased bleeding complications in the presence of acute kidney injury. Patients with known renal insufficiency may not be ideal candidates for dabigatran because there is a significantly increased serum concentration of dabigatran in the setting of renal disease compared with serum concentrations of dabigatran with normal renal function (Beasley, Unger, & Temple, 2011). Advanced practice nurses may consider obtaining a comprehensive serum metabolic profile before prescribing dabigatran as outpatient anticoagulation therapy for patients with atrial fibrillation to establish baseline renal function. Managing patients requiring outpatient anticoagulation therapy can present challenges for APNs, especially in the ED when there may only be a single encounter with patients. Dabigatran is a less complicated option for use with patients seen episodically because, unlike warfarin, routine monitoring of the coagulation status of patients is not needed. Providing patients with detailed information about the need for compliance with the prescribed pharmacological regimen is important, and it is critically important that patients understand when to seek care for potential complications such as GI bleeding.
Time: 23:1
CASE STUDY OUTCOME After a review of baseline diagnostic testing that included troponin, coagulation studies, and comprehensive metabolic profile that were all within normal limits, the APN discussed with B.R. the risks and benefits of dabigatran versus warfarin. The patient and the APN agreed that with his prior good health and current job-related travel requirements, dabigatran was the best first-line management strategy for preventing thromboembolic complications associated with his atrial fibrillation. The APN concurred that dabigatran was the safer choice, given the potential difficulty B.R. would have had with consistent monitoring of warfarin. The patient was able to verbalize an understanding of bleeding complications to watch for and when to seek additional treatment of potential complications. B.R. also verbalized an understanding of the need for follow-up to establish care for monitoring of the atrial fibrillation and potential complications. REFERENCES Beasley, B. N., Unger, E. F., & Temple, R. (2011). Anticoagulant options—Why the FDA approved a higher but not a lower dose of dabigatran. The New England Journal of Medicine, 364, 1788–1790. Berger, R. M., Salhanick, S. D., Chase, M., & Ganetsky, M. (2013). Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Annals of Emergency Medicine, 61, 475–479. Boehringer Ingelheim. (2013). PRADXA highlights of prescribing information. Retrieved from https:// www.pradaxa.com/about-pradaxa.jsp Connolly, S. J., Ezekowitz, M. D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., . . . Wallentin, L. (2009). Dabigatran versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine, 361, 1139–1151.
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
![[Bleeding complications under oral anticoagulation].](/assets/img/hold.png)
