Therapeutics
Review: Apixaban reduces bleeding and mortality compared with vitamin K antagonists Clinical impact ratings:
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Touma L, Filion KB, Atallah R, Eberg M, Eisenberg MJ. A metaanalysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists. Am J Cardiol. 2015; 115:533-41.
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Question
Commentary
What are the risks for bleeding and all-cause mortality with apixaban compared with vitamin K antagonists (VKAs)?
Touma and colleagues screened > 1000 articles and identified 5 RCTs comparing apixaban with VKAs. They found reduced bleeding with apixaban, including reduced intracranial bleeding—the most feared complication. Reduced bleeding seems to be a class effect of direct oral anticoagulants (DOACs); a recent meta-analysis of phase 3 RCTs showed reduced bleeding with DOACs compared with VKAs (1). The exception is increased gastrointestinal bleeding with dabigatran and rivaroxaban, but not with apixaban or edoxaban (2).
Review scope Included French- or English-language studies compared apixaban (2.5 mg or 5 mg, twice daily) with VKAs in adults ≥ 18 years of age. Outcomes included any bleeding, major or clinically relevant nonmajor bleeding, intracranial bleeding, and all-cause mortality.
Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Library (all to May 2014), and reference lists were searched for randomized controlled trials (RCTs). 5 RCTs (n = 25 576, mean age range 56 to 72 y, 16% to 67% women) met selection criteria. Trials included patients with atrial fibrillation (2 RCTs), venous thromboembolism (2 RCTs), and total knee replacement (1 RCT). Treatment duration ranged from 10 days to a median of 657 days, and follow-up ranged from 40 days to a median of 657 days. Low-molecular-weight heparin was included for ≥ 5 days during VKA dose titration in 2 RCTs. All trials had low risk for bias. Bleeding outcomes were assessed in the safety population (patients who received ≥ 1 dose of study drug).
Main results
In the review by Touma and colleagues, apixaban reduced overall mortality, but this result was driven mainly by the large Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial (n = 18 201) (3). In support of this finding, a review by Chai-Adisaksopha and colleagues showed reduced fatal bleeding with DOACs (1). Despite reduced rates of bleeding, clinicians are concerned about the lack of specific antidotes to DOACs. Among patients in the ARISTOTLE trial who had major bleeding, those treated with apixaban had fewer complications and reduced 30-day mortality than those in the warfarin group (4). Apixaban thus reduced risk for bleeding, and patients who did have bleeding had better outcomes than those receiving warfarin. This information allows clinicians to feel comfortable prescribing apixaban to appropriate patients.
Apixaban reduced bleeding, including intracranial bleeding, and all-cause mortality compared with VKAs (Table).
Thomas DeLoughery, MD, MACP, FAWM Oregon Health & Science University Portland, Oregon, USA
Conclusion In adults, apixaban reduces bleeding and all-cause mortality compared with vitamin K antagonists. Source of funding: No external funding. For correspondence: Dr. M.J. Eisenberg, McGill University, Montreal, QC, Canada. E-mail [email protected].
References 1. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124:2450-8. 2. Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and metaanalysis. Gastroenterology. 2013;145:105-12. 3. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-92.
Apixaban vs vitamin K antagonists (VKAs) in adults* Weighted event rates
At 40 to a median 657 d
I2
Outcomes
Number of trials (n)
Apixaban
VKAs
RRR (95% CI)
NNT (CI)
Any bleeding
4 (24 181)
23%
32%
27% (10 to 41)
12 (8 to 32)
84%
Major or CRNM bleeding
4 (23 977)
5.8%
9.6%
40% (12 to 60)
26 (18 to 87)
82%
Intracranial bleeding
3 (23 723)
0.5%
1.1%
58% (42 to 69)
158 (133 to 219)
0%
All-cause mortality
5 (24 637)
5.3%
6.0%
11% (1 to 19)
153 (89 to 1676)
0%
4. Hylek EM, Held C, Alexander JH, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): predictors, characteristics, and clinical outcomes. J Am Coll Cardiol. 2014;63:2141-7.
*CRNM = clinically relevant nonmajor; other abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from control event rates and relative risks in article using a random-effects model.
姝 2015 American College of Physicians JC2 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/28/2015
Annals of Internal Medicine
21 April 2015
Review: Apixaban reduces bleeding and mortality compared with vitamin K antagonists Clinical impact ratings:
多多多多多夞夞
多多多多多多夞
Touma L, Filion KB, Atallah R, Eberg M, Eisenberg MJ. A metaanalysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists. Am J Cardiol. 2015; 115:533-41.
多多多多多夞夞
Question
Commentary
What are the risks for bleeding and all-cause mortality with apixaban compared with vitamin K antagonists (VKAs)?
Touma and colleagues screened > 1000 articles and identified 5 RCTs comparing apixaban with VKAs. They found reduced bleeding with apixaban, including reduced intracranial bleeding—the most feared complication. Reduced bleeding seems to be a class effect of direct oral anticoagulants (DOACs); a recent meta-analysis of phase 3 RCTs showed reduced bleeding with DOACs compared with VKAs (1). The exception is increased gastrointestinal bleeding with dabigatran and rivaroxaban, but not with apixaban or edoxaban (2).
Review scope Included French- or English-language studies compared apixaban (2.5 mg or 5 mg, twice daily) with VKAs in adults ≥ 18 years of age. Outcomes included any bleeding, major or clinically relevant nonmajor bleeding, intracranial bleeding, and all-cause mortality.
Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Library (all to May 2014), and reference lists were searched for randomized controlled trials (RCTs). 5 RCTs (n = 25 576, mean age range 56 to 72 y, 16% to 67% women) met selection criteria. Trials included patients with atrial fibrillation (2 RCTs), venous thromboembolism (2 RCTs), and total knee replacement (1 RCT). Treatment duration ranged from 10 days to a median of 657 days, and follow-up ranged from 40 days to a median of 657 days. Low-molecular-weight heparin was included for ≥ 5 days during VKA dose titration in 2 RCTs. All trials had low risk for bias. Bleeding outcomes were assessed in the safety population (patients who received ≥ 1 dose of study drug).
Main results
In the review by Touma and colleagues, apixaban reduced overall mortality, but this result was driven mainly by the large Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial (n = 18 201) (3). In support of this finding, a review by Chai-Adisaksopha and colleagues showed reduced fatal bleeding with DOACs (1). Despite reduced rates of bleeding, clinicians are concerned about the lack of specific antidotes to DOACs. Among patients in the ARISTOTLE trial who had major bleeding, those treated with apixaban had fewer complications and reduced 30-day mortality than those in the warfarin group (4). Apixaban thus reduced risk for bleeding, and patients who did have bleeding had better outcomes than those receiving warfarin. This information allows clinicians to feel comfortable prescribing apixaban to appropriate patients.
Apixaban reduced bleeding, including intracranial bleeding, and all-cause mortality compared with VKAs (Table).
Thomas DeLoughery, MD, MACP, FAWM Oregon Health & Science University Portland, Oregon, USA
Conclusion In adults, apixaban reduces bleeding and all-cause mortality compared with vitamin K antagonists. Source of funding: No external funding. For correspondence: Dr. M.J. Eisenberg, McGill University, Montreal, QC, Canada. E-mail [email protected].
References 1. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124:2450-8. 2. Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and metaanalysis. Gastroenterology. 2013;145:105-12. 3. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-92.
Apixaban vs vitamin K antagonists (VKAs) in adults* Weighted event rates
At 40 to a median 657 d
I2
Outcomes
Number of trials (n)
Apixaban
VKAs
RRR (95% CI)
NNT (CI)
Any bleeding
4 (24 181)
23%
32%
27% (10 to 41)
12 (8 to 32)
84%
Major or CRNM bleeding
4 (23 977)
5.8%
9.6%
40% (12 to 60)
26 (18 to 87)
82%
Intracranial bleeding
3 (23 723)
0.5%
1.1%
58% (42 to 69)
158 (133 to 219)
0%
All-cause mortality
5 (24 637)
5.3%
6.0%
11% (1 to 19)
153 (89 to 1676)
0%
4. Hylek EM, Held C, Alexander JH, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): predictors, characteristics, and clinical outcomes. J Am Coll Cardiol. 2014;63:2141-7.
*CRNM = clinically relevant nonmajor; other abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from control event rates and relative risks in article using a random-effects model.
姝 2015 American College of Physicians JC2 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/28/2015
Annals of Internal Medicine
21 April 2015
