Therapeutics
After initial anticoagulation for a first unprovoked venous thromboembolism, aspirin reduced recurrence Clinical impact ratings:
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Simes J, Becattini C, Agnelli G, et al; INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism). Aspirin for the prevention of recurrent venous thromboembolism: The INSPIRE Collaboration. Circulation. 2014; 130:1062-71.
多多多多多夞夞
Questions In patients who completed a course of anticoagulant therapy after a first unprovoked venous thromboembolism (VTE), does aspirin prevent recurrence? Do effects differ in subgroups?
Methods Design: Individual patient data analysis (INSPIRE Collaboration) of 2 randomized placebo-controlled trials (WARFASA* and ASPIRE†). Australian New Zealand Clinical Trials Registry ACTRN12611000684921. Allocation: {Concealed}*†.‡ Blinding: Blinded‡ {patients, clinicians, data collectors, and outcome assessors or adjudicators}*†. Follow-up period: Maximum 4 years (median 30 mo). Setting: {25 centers in Austria and Italy in WARFASA*, and 56 centers in 5 countries in ASPIRE†}. Patients: 1225 patients (mean age 57 y, 58% men) who had a first unprovoked (no known risk factors) proximal deep venous thrombosis or pulmonary embolism (PE) and completed initial treatment with warfarin, heparin, or an equivalent anticoagulant. Exclusion criteria included other indications for anticoagulant therapy, increased risk for bleeding, use of cyclooxygenase (COX)–1 or COX–2 inhibitors, or life expectancy < 6 months. Intervention: Enteric-coated aspirin, 100 mg/d (n = 616), or placebo (n = 609). Outcomes: Major outcomes included recurrent VTE (new symptomatic VTE or fatal PE) and major or clinically relevant nonmajor bleeding. Patient follow-up: 99.9% (modified intention-to-treat analysis included all patients who received ≥ 1 dose of study drug).
Main results
*Rabinowitz I. ACP Journal Club. Aspirin reduced recurrence of venous thromboembolism (VTE) after a first-ever, unprovoked VTE. Ann Intern Med. 2012;157(8):JC4-3. †Deloughery T. ACP Journal Club. Aspirin did not reduce recurrence after a first-ever, unprovoked venous thromboembolism. Ann Intern Med. 2013;158(6):JC2. ‡See Glossary. Source of funding: National Health and Medical Research Council. For correspondence: Dr. J. Simes, University of Sydney, Sydney, New South Wales, Australia. E-mail [email protected].
Commentary Despite evidence showing a benefit from indefinite treatment (1, 2), choosing the duration of anticoagulation after an unprovoked episode of acute VTE remains challenging. The decision is based on assessment of risks for recurrence without anticoagulation (5% to 10%/y) and major bleeding due to anticoagulants (1% to 10%/y). Although VTE and bleeding risk calculators have been developed, no studies have assessed whether their joint use identifies patients who will benefit from long-term anticoagulation. The findings of the INSPIRE Collaboration add to the available evidence. INSPIRE examined aspirin use after initial treatment of VTE by combining data from 2 large randomized placebo-controlled trials with similar designs (WARFASA and ASPIRE). The collaboration was planned early in the trials. The finding that aspirin reduced VTE by 30% contrasts with results from studies of anticoagulants, which reported reductions of 80% to 90% (1, 2). Ideally, a direct comparison would inform the relative effects of anticoagulants and aspirin on VTE. Nevertheless, the magnitude and consistency of the difference suggest that aspirin, although efficacious, offers less protection from recurrent VTE than fulldose anticoagulation.
Aspirin reduced recurrent VTE compared with placebo (Table). Effects of aspirin on recurrent VTE were consistent in prespecified subgroups (sex, age, body mass index, duration of initial anticoagulation, and type of qualifying VTE). The effect of aspirin on bleeding is reported in the Table.
The lack of a statistically significant increase in bleeding with aspirin in INSPIRE does not preclude an increased risk. Both the point estimate and confidence interval are consistent with a small absolute increase, as is a large body of evidence on chronic aspirin use.
Conclusion
Given the trade-offs, clinicians should engage patients in the decision-making process when determining long-term strategies. Recognizing the importance of patient preference and incorporating a shared decision-making approach should allay physician concerns about recommending the “correct” choice— there is no definitive choice for all patients. For patients who choose to forgo indefinite anticoagulation, INSPIRE provides high-quality evidence that aspirin can reduce their VTE risk, with an increase in major bleeding of < 1%.
In patients who completed initial anticoagulant therapy after a first unprovoked venous thromboembolism, aspirin reduced recurrence.
Aspirin vs placebo after completion of anticoagulant therapy for a first-ever, unprovoked venous thromboembolism (VTE)§ Outcomes
Event rates Aspirin
Recurrent VTE||
13%
Placebo 18%
At a median 30 mo RRR (95% CI) 30% (9 to 46)
Andrew S. Dunn, MD, MPH Mount Sinai Health System New York, New York, USA
NNT (CI) 19 (12 to 60)
References
RRI (CI)
NNH
49% (⫺28 to 207)
Not significant
1. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340:901-7.
§Abbreviations defined in Glossary. RRR, RRI, NNT, and CI calculated from placebo event rates and hazard ratios in article.
2. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363: 2499-510.
Major or clinically relevant nonmajor bleeding
2.9%
2.0%
||Deep venous thrombosis alone (9.6% vs 14%, P = 0.01) or pulmonary embolism with or without deep venous thrombosis (4.7% vs 6.9%, P = 0.08).
17 February 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015
JC5
姝 2015 American College of Physicians
After initial anticoagulation for a first unprovoked venous thromboembolism, aspirin reduced recurrence Clinical impact ratings:
多多多多多多夞
多多多多多多夞
Simes J, Becattini C, Agnelli G, et al; INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism). Aspirin for the prevention of recurrent venous thromboembolism: The INSPIRE Collaboration. Circulation. 2014; 130:1062-71.
多多多多多夞夞
Questions In patients who completed a course of anticoagulant therapy after a first unprovoked venous thromboembolism (VTE), does aspirin prevent recurrence? Do effects differ in subgroups?
Methods Design: Individual patient data analysis (INSPIRE Collaboration) of 2 randomized placebo-controlled trials (WARFASA* and ASPIRE†). Australian New Zealand Clinical Trials Registry ACTRN12611000684921. Allocation: {Concealed}*†.‡ Blinding: Blinded‡ {patients, clinicians, data collectors, and outcome assessors or adjudicators}*†. Follow-up period: Maximum 4 years (median 30 mo). Setting: {25 centers in Austria and Italy in WARFASA*, and 56 centers in 5 countries in ASPIRE†}. Patients: 1225 patients (mean age 57 y, 58% men) who had a first unprovoked (no known risk factors) proximal deep venous thrombosis or pulmonary embolism (PE) and completed initial treatment with warfarin, heparin, or an equivalent anticoagulant. Exclusion criteria included other indications for anticoagulant therapy, increased risk for bleeding, use of cyclooxygenase (COX)–1 or COX–2 inhibitors, or life expectancy < 6 months. Intervention: Enteric-coated aspirin, 100 mg/d (n = 616), or placebo (n = 609). Outcomes: Major outcomes included recurrent VTE (new symptomatic VTE or fatal PE) and major or clinically relevant nonmajor bleeding. Patient follow-up: 99.9% (modified intention-to-treat analysis included all patients who received ≥ 1 dose of study drug).
Main results
*Rabinowitz I. ACP Journal Club. Aspirin reduced recurrence of venous thromboembolism (VTE) after a first-ever, unprovoked VTE. Ann Intern Med. 2012;157(8):JC4-3. †Deloughery T. ACP Journal Club. Aspirin did not reduce recurrence after a first-ever, unprovoked venous thromboembolism. Ann Intern Med. 2013;158(6):JC2. ‡See Glossary. Source of funding: National Health and Medical Research Council. For correspondence: Dr. J. Simes, University of Sydney, Sydney, New South Wales, Australia. E-mail [email protected].
Commentary Despite evidence showing a benefit from indefinite treatment (1, 2), choosing the duration of anticoagulation after an unprovoked episode of acute VTE remains challenging. The decision is based on assessment of risks for recurrence without anticoagulation (5% to 10%/y) and major bleeding due to anticoagulants (1% to 10%/y). Although VTE and bleeding risk calculators have been developed, no studies have assessed whether their joint use identifies patients who will benefit from long-term anticoagulation. The findings of the INSPIRE Collaboration add to the available evidence. INSPIRE examined aspirin use after initial treatment of VTE by combining data from 2 large randomized placebo-controlled trials with similar designs (WARFASA and ASPIRE). The collaboration was planned early in the trials. The finding that aspirin reduced VTE by 30% contrasts with results from studies of anticoagulants, which reported reductions of 80% to 90% (1, 2). Ideally, a direct comparison would inform the relative effects of anticoagulants and aspirin on VTE. Nevertheless, the magnitude and consistency of the difference suggest that aspirin, although efficacious, offers less protection from recurrent VTE than fulldose anticoagulation.
Aspirin reduced recurrent VTE compared with placebo (Table). Effects of aspirin on recurrent VTE were consistent in prespecified subgroups (sex, age, body mass index, duration of initial anticoagulation, and type of qualifying VTE). The effect of aspirin on bleeding is reported in the Table.
The lack of a statistically significant increase in bleeding with aspirin in INSPIRE does not preclude an increased risk. Both the point estimate and confidence interval are consistent with a small absolute increase, as is a large body of evidence on chronic aspirin use.
Conclusion
Given the trade-offs, clinicians should engage patients in the decision-making process when determining long-term strategies. Recognizing the importance of patient preference and incorporating a shared decision-making approach should allay physician concerns about recommending the “correct” choice— there is no definitive choice for all patients. For patients who choose to forgo indefinite anticoagulation, INSPIRE provides high-quality evidence that aspirin can reduce their VTE risk, with an increase in major bleeding of < 1%.
In patients who completed initial anticoagulant therapy after a first unprovoked venous thromboembolism, aspirin reduced recurrence.
Aspirin vs placebo after completion of anticoagulant therapy for a first-ever, unprovoked venous thromboembolism (VTE)§ Outcomes
Event rates Aspirin
Recurrent VTE||
13%
Placebo 18%
At a median 30 mo RRR (95% CI) 30% (9 to 46)
Andrew S. Dunn, MD, MPH Mount Sinai Health System New York, New York, USA
NNT (CI) 19 (12 to 60)
References
RRI (CI)
NNH
49% (⫺28 to 207)
Not significant
1. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340:901-7.
§Abbreviations defined in Glossary. RRR, RRI, NNT, and CI calculated from placebo event rates and hazard ratios in article.
2. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363: 2499-510.
Major or clinically relevant nonmajor bleeding
2.9%
2.0%
||Deep venous thrombosis alone (9.6% vs 14%, P = 0.01) or pulmonary embolism with or without deep venous thrombosis (4.7% vs 6.9%, P = 0.08).
17 February 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015
JC5
姝 2015 American College of Physicians
