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Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines | February 2012
Introduction to the Ninth Edition:

Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest
Physicians Evidence-Based Clinical Practice
Guidelines FREE TO VIEW
Gordon H. Guyatt, MD, FCCP; Elie A. Akl, MD, PhD, MPH; Mark Crowther, MD; Holger J.
Schnemann, MD, PhD, FCCP; David D. Gutterman, MD, FCCP; Sandra Zelman Lewis, PhD
Author and Funding Information
Chest. 2012;141(2_suppl):48S-52S. doi:10.1378/chest.11-2286
Text Size: A A A
Article
Tables
References
Abstract
Abstract | The New Process in AT9Dealing With Conflict of Interest | Evidence Summaries |
Reevaluation of Evidence | Values and Preferences | Impact of Innovations on the Recommendations |
Other Innovations in AT9 | Conclusion | Acknowledgments | Abbreviations | References
The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines differs substantially from the prior versions both
in process and in content. In this introduction, we describe some of the differences and the rationale for
the changes.
We would like to begin by acknowledging the contributions of the visionaries whose work on past
editions of these guidelines have allowed the current panel to develop this edition using the changes noted
herein. First, James E. Dalen, respected clinician and researcher, while President of the American College
of Chest Physicians (ACCP), had the foresight not only to propose the original consensus conference on
the controversial issues of the indications for antithrombotics, antiplatelet agents, and thrombolytics for
the prevention and treatment of cardiovascular disorders but also to invite Jack Hirsh, an extremely
productive scientist and leader in the field of thrombosis, to join him in leading this important project. Drs
Hirsh and Dalen brought a panel of leading experts together for the first antithrombotic guideline 1 in
1986. Dr Dalen was co-editor of the first six guidelines from 1986 to 2001.
Dr Hirsh is, to an extraordinary extent, responsible not only for creating the platform that has made
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (AT9) possible but also for the advances from
Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition) (AT8) to AT9. It was not only the creation of an expert panela
standard feature of specialty society clinical practice guidelines from the outsetthat made the
antithrombotic guidelines extremely successful. Dr Hirsh, an accomplished basic science researcher and a
brilliant clinical trialist, deeply understood the value of what was to become more than a decade later
evidence-based medicine. He recruited one of the world leaders in the burgeoning field of clinical
epidemiology, David Sackett, to play a major role in the guidelines. Drs Hirsh and Sackett developed and
applied an innovative system of rating the quality of evidence and strength of recommendations that was
at the time unique to specialty guidelines. The combined impact of the authoritative, carefully considered
recommendations and explicit acknowledgment of the quality of evidence and strength of
recommendations immediately made these guidelines the reference standard for antithrombotic therapy
around the world.
Under Dr Hirshs leadership, the guidelines more than kept pace with advances in the science of guideline
methodology and continued to improve with each iteration. Each new edition provided a model
incorporating not only the latest evidence regarding antithrombotic therapy but also advances in specialtybased guidelines and therefore maintained preeminence in the field of thrombosis.
As Dr Hirsh was stepping down from the leadership of the guidelines in 2007, his insight led him to
question the reliance on expert opinion that provided the basis for the first eight iterations of the
antithrombotic guidelines. Reviewing his experienceand in the process giving new life to an idea
suggested decades earlier but seldom applied2Dr Hirsh concluded that the conflict of interest of leading
experts was highly problematic.3 Furthermore, the problem arose not only from their financial but equally
or perhaps more important, their intellectual conflict of interest. This revelation and the changes in
process that Dr Hirsh suggested as a solution to the problem had a profound impact on the leadership to
whom he was passing the torch. These changes underlie all the innovations in AT9.
The New Process in AT9Dealing With Conflict of Interest

The solution that Dr Hirsh proposed was endorsed by the ACCP leadership and implemented in AT9. That
solution is to give primary leadership and responsibility for each article not to a thrombosis expert but to a
methodologist who, in almost all cases, also is a practicing physician without important conflicts of
interest4,5 (Table 1). These editors of each article had specific training in ACCPs approach to rating the
quality of evidence and grading strength of recommendations (see Evidence Summaries section).
Further, building on the work of prior guideline groups,6 the process stipulated that although conflicted
thrombosis experts could engage in discussion and even draft evidence summaries, they would be
excluded from the final decisions regarding quality of evidence and direction and strength of
recommendations. Intellectual conflicts received the same attention as financial conflicts. Readers of the
guidelines can find in the online data supplements to AT9 articles a recommendation-by-recommendation
accounting of the intellectual and financial conflicts of each panel member. The most important changes
in AT9 content have flowed directly from this change in process.
Table 1 Major Innovations in AT9
View Large | Save Table
Evidence Summaries
The Sixth ACCP Consensus Conference on Antithrombotic Therapy (AT6), 7 published in 2001, adopted
an approach to rating quality of evidence and strength of recommendations 8 that presaged that of the
Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) working group, 9 itself
adopted with minor modifications for AT810 and for all ACCP guidelines.11 AT8, like AT6 and the Seventh
ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines (AT7), 12
underwent thorough editing and review of the quality of evidence, including in many cases a careful
assessment of single studies by topic editors and the guideline executive committee. Nevertheless, many
of the topic editors did not have methodologic training or, as was the case in AT8, specific training in the
ACCP-GRADE approach. The result was that in AT8, the ACCP-GRADE approach often was not applied
with optimal rigor, and authors produced very few of the summary tables that are the hallmark end
product of the GRADE process.
There are two types of such tables: evidence profiles and summary of findings. Evidence profiles
summarize the quality of a body of evidence for each relevant outcome and, when evidence comes from
randomized trials, include a presentation of reviewers assessment of risk of bias, precision, consistency,
directness, and publication bias.5 Readers of AT9 can find the evidence profiles in the online data
supplements. The text in the main AT9 articles includes the more succinct summary of findings tables,
which include the overall quality assessment as well as relative and absolute effect sizes for each
outcome. We did not succeed in the lofty goal of producing a summary of findings table for each
recommendation, but readers will find these for most major and potentially controversial
recommendations. Readers will find > 10 such tables in most articles and > 20 in some articles.
Producing these tables forces a rigor of thinking achievable in few other ways. Creating a large number of
evidence profiles provides deep insight into the ACCP-GRADE approach to assessing the quality of
evidence and strength of recommendations. Along with recruitment of GRADE-expert topic editors,
production of evidence profiles and summary of findings tables is responsible for the increased
methodologic rigor of AT9.
We also tried to apply a rigorous approach to choosing the format of these tables, an issue that has
generated some controversy within the GRADE working group. Per Olav Vandvik, Holger Schnemann,
and Nancy Santesso led the group in a formal study in which AT9 panelists expressed their view of the
optimal presentation of the tables.5 The results have not only guided the presentation of evidence profiles
and summary of findings in AT9 but also provided one of the recommended options for the GRADE
working group.
Reevaluation of Evidence
Relying on the perspective of unconflicted methodologists, rigorously applying the GRADE approach,
and excluding those with financial and intellectual conflict of interests from bottom-line decisions
regarding the quality of evidence and strength of recommendations led to reevaluations of previously
existing evidence (Table 1). For instance, application of the ACCP-GRADE approach requires the
distinction between patient-important and surrogate outcomes. The first eight editions of the
antithrombotic guidelines failed to fully recognize the implications of a surrogate widely used in
thrombosis prevention trialsasymptomatic, screening-detected thrombosis. Use of this surrogate creates
major problems in making the trade-off between patient-important outcomes (thrombosis and serious
bleeding). For instance, if one knows that an intervention increases serious bleeding by 20 events in 1,000
patients but reduces asymptomatic thrombosis by 100 in 1,000, what is the net benefit? Establishing net
benefit in outcomes important to patients requires knowing the symptomatic DVT and symptomatic
pulmonary embolism reduction represented by the reduction in 100 asymptomatic events. Dr Hirsh and
John Eikelboom led the prevention topic editors in developing innovative approaches to dealing with the
problem of inferring the impact of thromboprophylaxis on symptomatic thrombosis from studies that
relied to a considerable extent on detection of asymptomatic events. 13 The available approaches, although
representing a step forward, all have limitations and highlight the need for studies that directly measure
symptomatic thrombosis without venographic or ultrasound surveillance.
As a result of a reevaluation led by Dr Eikelboom, one consequence of the recognition that measurement
of patient-important events in a naturalistic clinical setting (as opposed to in the context of venographic or
ultrasonographic screening for asymptomatic thrombosis) was a differing perspective on the use of aspirin
in thromboprophylaxis in orthopedic surgery. The authors of AT8 had concluded that there was highquality evidence justifying a strong recommendation against aspirin as the sole agent for
thromboprophylaxis in surgical patients. Authors of AT9 focused on results from a very large trial using
concealed randomization and blinding and achieving near-complete follow-up. 14 After an exhaustive and
repeated discussion involving the authors of all the prevention articles, and ultimately the entire panel,
AT9 authors concluded that the trial provides moderate-quality evidence supporting the use of aspirin,
which is now offered as an option for thromboprophylaxis in patients undergoing major orthopedic
procedures.15 AT9 authors concluded that there is low-quality evidence supporting a weak
recommendation of low-molecular-weight heparin over aspirin in these patients.
The GRADE approach defines quality of evidence as our level of confidence in estimates of diagnostic or
treatment effect to support a particular recommendation. 16 In general, the changing perspectives on
evidence led to the conclusion that we often could not be as confident in estimates of effect as previously
believed. Readers of AT9 will often find, therefore, that some of the evidence previously rated as high
quality is now moderate, and evidence previously rated as moderate quality is now low.
Values and Preferences

Serial iterations of AT9 dating back to AT6 have gradually put increasing emphasis on patient values and
preferences. For the first time, the AT7 panel made the assumptions about values and preferences explicit.
The AT9 panel has accelerated that process by conducting a systematic review 17 of the relevant research
of empirical investigations of values and preferences of patients regarding antithrombotic therapy. Based
on that review, AT9 panelists conducted a value rating exercise that provided the basis for values and
preference judgments within AT9, judgments that are summarized in the introductory section of each
article.13 The judgments are more explicit and quantitative than any previous guideline. For example, we
estimated that on average, patients experience the disutility of a GI bleed more or less equally to that of
VTE but only one-third of the disutility of a stroke.
Among the findings of the systematic review of patient values and preferences regarding antithrombotic
treatment are the heterogeneity of results between studies and the wide variability in values and
preferences among patients. Because the core characteristic of a strong recommendation is the belief that
across the range of values and preferences, virtually all informed patients will make the same choice, the
wide variability in patient values and preferences makes strong recommendations less likely. 18
Impact of Innovations on the Recommendations

Readers of AT9 will find many weak recommendations replacing the strong recommendations of AT8.
One major reason for this change is the more critical look at the evidence and the resulting inferences that
some evidence is lower quality than previously believed. A second is the recognition of variability in
values and preferences. Third, in the small number of controversial recommendations that came to a
formal vote using anonymous electronic voting, we required the endorsement of > 80% of panelists to
make a strong recommendation. Finally, the exclusion of conflicted experts, who often hold strong
opinions about optimal management approaches, from final decisions regarding quality of evidence and
strength of recommendations also may have contributed.
Other Innovations in AT9

For the first time, each panel included a frontline clinician not involved in thrombosis research. The goal
of including these individuals was to ensure that recommendations considered the full realities of clinical
practice as viewed by those outside the research environment and to support efforts to make the phrasing
of recommendations more user friendly and implementable.
A limitation of AT8 was the very inconsistent approaches to assessing bleeding risk. Sam Schulman,
author of the bleeding risk article in AT8,19 took responsibility for developing the AT9 approach to
bleeding and ensuring that it was consistently applied across chapters. 5
To address issues of economic efficiency, we included resource use consultants on the AT9 article
panels charged with making recommendations. They developed a transparent and systematic
methodology to address questions for which resource use might change the direction or strength of
recommendations.5
We made an intensive effort to remove duplication between articles and to harmonize recommendations
between related articles. An important strategy was to include topic editors and deputy editors as panelists
from both articles when two had overlapping issues.
Finally, for the first time, the antithrombotic guidelines have addressed issues of diagnosis. Shannon
Bates and Roman Jaeschke led a panel that took on the challenging task of applying the newly developed
GRADE methodology for recommendations regarding the diagnosis of DVT.20
Conclusion
Building on the seminal work of Drs Hirsh and Dalen and their colleagues over the 20-year history of the
ACCP antithrombotic guidelines, AT9 has made a number of changes in process, resulting in differences
in the approach to making recommendations and their content. Past iterations of these guidelines have
celebrated new high-quality evidence and the strong recommendations that such evidence warrants. The
insights from AT9 include the persisting limitations in evidence quality (particularly with respect to the
use of surrogate outcomes in prophylaxis trials) and the appropriateness of weak recommendations that
reflect our lack of confidence in effect estimates and the variability in patient values and preferences. We
believe that the objective, rigorous application of the science of guideline development will ultimately
best serve our patients.
Acknowledgments
Other contributions: The authors thank Rachel Gutterman, BA, and Joe Ornelas, DC, for their assistance
in managing this complex project.
Financial/nonfinancial disclosures: In summary, the authors have reported to CHEST the following
conflicts of interest: Dr Crowther has served on various advisory boards, has assisted in the preparation of
educational materials, and has sat on data safety and monitoring boards. His institution has received
research funds from the following companies: Leo Pharma A/S, Pfizer Inc, Boerhinger Ingelheim GmbH,
Bayer Healthcare Pharmaceuticals, Octapharm AG, CSL Behring, and Artisan Pharma. Personal total
compensation for these activities over the past 3 years totals less than US $10,000. Dr Gutterman has had
the following relationships that are entirely unrelated to the AT9 guidelines: ACCP President,
GlaxoSmithKline plc grant to study vasodilation in adipose tissue, National Institutes of Health grant to
study human coronary dilation, and GE Healthcare consultation on a study for ECG evaluation of chronic
heart disease. Drs Guyatt and Schnemann are co-chairs of the GRADE Working Group, and Dr Akl is a
member and prominent contributor to the GRADE Working Group. Dr Lewis is a full-time employee of
the ACCP.
Role of sponsors: The sponsors played no role in the development of these guidelines. Sponsoring
organizations cannot recommend panelists or topics, nor are they allowed prepublication access to the
manuscripts and recommendations. Guideline panel members, including the chair, and members of the
Health & Science Policy Committee are blinded to the funding sources. Further details on the Conflict of
Interest Policy are available online at http://chestnet.org.
Endorsements: This guideline is endorsed by the American Association for Clinical Chemistry, the
American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, the
American Society of Hematology, and the International Society of Thrombosis and Hematosis.
Abbreviations
ACCP
American College of Chest Physicians
AT6
Sixth ACCP Consensus Conference on Antithrombotic Therapy
AT7
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based

Guidelines
AT8
Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition)
AT9
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines
GRADE Grades of Recommendations, Assessment, Development, and Evaluation
References
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Guyatt GH, Norris SL, Schulman S, et al. Methodology for the development of antithrombotic therapy
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American College of Chest Physicians evidence-based clinical practice
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Schnemann H, Osborne M, Moss J, et al. An official American Thoracic Society Policy Statement:
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Guyatt G, Schunmann H, Cook D, Jaeschke R, Pauker S, Bucher H. American College of Chest
Physicians American College of Chest Physicians Grades of recommendation for antithrombotic
agents. Chest. 2001;119suppl 1:3S-7S. [CrossRef] [PubMed]
9
Guyatt GH, Oxman AD, Vist GE, et al; GRADE Working Group GRADE Working Group GRADE: an
emerging consensus on rating quality of evidence and strength of
recommendations. BMJ. 2008;3367650:924-926. [CrossRef] [PubMed]
10
Guyatt GH, Cook DJ, Jaeschke R, Pauker SG, Schnemann HJ. Grades of recommendation for
antithrombotic agents: American College of Chest Physicians evidence-based clinical practice guidelines
(8th edition). Chest. 2008;133suppl 6:123S-131S. [CrossRef] [PubMed]
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Guyatt G, Gutterman D, Baumann MH, et al. Grading strength of recommendations and quality of
evidence in clinical guidelines: report from an American College of Chest Physicians task
force. Chest. 2006;1291:174-181. [CrossRef] [PubMed]
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American College of Chest PhysiciansAmerican College of Chest Physicians The seventh ACCP
conference on antithrombotic and thrombolytic therapy: evidence-based guidelines. Chest. 2004;126suppl
3:1S-703S. [CrossRef]
13
Guyatt GH, Eikelboom JW, Gould MK, et al. Approach to outcome measurement in the prevention of
thrombosis in surgical and medical patients: antithrombotic therapy and prevention of thrombosis, 9th ed:
American College of Chest Physicians evidence-based clinical practice
guidelines. Chest. 2012;1412suppl:e185S-e194S. [CrossRef] [PubMed]
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Pulmonary Embolism Prevention (PEP) trial Collaborative GroupPulmonary Embolism Prevention (PEP)
trial Collaborative Group Prevention of pulmonary embolism and deep vein thrombosis with low dose
aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000;3559212:12951302. [CrossRef] [PubMed]
15
Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: antithrombotic therapy and
prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice
guidelines. Chest. 2012;1412suppl:e89S-e119S. [CrossRef] [PubMed]
16
Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schnemann HJ. GRADE Working
Group GRADE Working Group What is quality of evidence and why is it important to
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MacLean S, Mulla S, Akl EA, et al. Patient values and preferences in decision making for antithrombotic
therapy: a systematic review: antithrombotic therapy and prevention of thrombosis, 9th ed: American
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Guyatt GH, Oxman AD, Kunz R, et al; GRADE Working Group GRADE Working Group Going from
evidence to recommendations. BMJ. 2008;3367652:1049-1051. [CrossRef] [PubMed]
19
Schulman S, Beyth RJ, Kearon C, Levine MN. American College of Chest Physicians American College
of Chest Physicians Hemorrhagic complications of anticoagulant and thrombolytic treatment: American
College of Chest Physicians evidence-based clinical practice guidelines (8th
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20
Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT: antithrombotic therapy and prevention of
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guidelines. Chest. 2012;1412suppl:e351S-e418S. [PubMed]
Abstrak | Proses Baru di AT9-Berurusan Dengan Benturan Kepentingan | Ringkasan

bukti | Reevaluasi Bukti | Nilai-nilai dan Preferences | Dampak Inovasi pada
Rekomendasi | Inovasi lainnya di AT9 | kesimpulan | Ucapan Terima Kasih | singkatan
| Referensi
The antitrombotik Terapi dan Pencegahan Trombosis, ed 9: American College of
Pedoman Praktek Klinis Bukti Berbasis Chest Physicians berbeda secara substansial
dari versi sebelumnya baik dalam proses dan dalam konten. Dalam pendahuluan ini,
kami akan menjelaskan beberapa perbedaan dan alasan untuk perubahan.
Kami ingin memulai dengan mengakui kontribusi dari para visioner yang bekerja
pada edisi terakhir dari panduan ini telah memungkinkan panel saat ini untuk
mengembangkan edisi ini menggunakan perubahan dicatat di sini. Pertama, James
E. Dalen, dokter dihormati dan peneliti, sementara Presiden American College of
Chest Physicians (ACCP), memiliki pandangan ke depan tidak hanya untuk
mengusulkan konferensi konsensus asli pada isu-isu kontroversial indikasi untuk
antithrombotics, agen antiplatelet, dan trombolitik untuk pencegahan dan
pengobatan gangguan kardiovaskular, tetapi juga mengundang Jack Hirsh, seorang
ilmuwan yang sangat produktif dan pemimpin dalam bidang trombosis, untuk
bergabung dengannya dalam memimpin proyek penting ini. Drs Hirsh dan Dalen
membawa panel ahli terkemuka bersama-sama untuk guideline1 antitrombotik
pertama pada tahun 1986. Dr Dalen adalah co-editor dari enam pedoman pertama
1986-2001.
Dr Hirsh adalah, ke mana yang luar biasa, tidak hanya bertanggung jawab untuk
menciptakan platform yang telah membuat antitrombotik Terapi dan Pencegahan
Trombosis, ed 9: American College of Chest Physicians Bukti-Berdasarkan Pedoman
Praktik Klinis (AT9) mungkin tetapi juga untuk kemajuan dari antitrombotik dan
trombolitik Terapi: American College of Chest Physicians Bukti Berbasis klinis
Pedoman Praktik (8 Edition) (AT8) ke AT9. Itu tidak hanya penciptaan panel-fitur
standar ahli masyarakat khusus pedoman praktek klinis dari awal-yang membuat
pedoman antitrombotik sangat sukses. Dr Hirsh, seorang peneliti dasar ilmu dicapai
dan trialist klinis brilian, sangat memahami nilai apa yang menjadi lebih dari satu
dekade kemudian kedokteran berbasis bukti. Dia merekrut salah satu pemimpin
dunia dalam bidang yang sedang berkembang epidemiologi klinis, David Sackett,
memainkan peran utama dalam pedoman. Drs Hirsh dan Sackett dikembangkan dan
diterapkan sistem inovatif dari penilaian kualitas bukti dan kekuatan rekomendasi
yang pada saat yang unik untuk pedoman khusus. Dampak gabungan dari
berwibawa, rekomendasi seksama dan pengakuan eksplisit dari kualitas bukti dan
kekuatan rekomendasi segera membuat pedoman ini standar referensi untuk terapi
antitrombotik di seluruh dunia.
Di bawah kepemimpinan Dr Hirsh ini, pedoman lebih dari terus berpacu dengan
kemajuan ilmu metodologi pedoman dan terus meningkatkan dengan setiap iterasi.
Setiap edisi baru tersedia model menggabungkan tidak hanya bukti terbaru
mengenai terapi antitrombotik tetapi juga kemajuan dalam pedoman berbasis
khusus dan karena itu dipelihara keunggulan di bidang trombosis.
Seperti Dr Hirsh mengundurkan diri dari kepemimpinan pedoman pada tahun 2007,
wawasan membuatnya mempertanyakan ketergantungan pada pendapat ahli yang
memberikan dasar untuk pertama delapan iterasi dari pedoman antitrombotik.
Meninjau nya pengalaman-dan dalam proses memberi kehidupan baru bagi ide
yang disarankan dekade sebelumnya tapi jarang applied2-Dr Hirsh menyimpulkan
bahwa konflik kepentingan dari para ahli terkemuka itu sangat problematic.3
Selanjutnya, masalah muncul tidak hanya dari mereka keuangan tapi sama atau
mungkin lebih penting, konflik intelektual minat mereka. wahyu ini dan perubahan
proses yang Dr Hirsh disarankan sebagai solusi untuk masalah ini memiliki dampak
yang mendalam pada kepemimpinan kepada siapa ia melewati obor. Perubahan ini
melandasi semua inovasi di AT9.
Proses Baru di AT9-Berurusan Dengan Benturan Kepentingan
| Referensi
Solusi yang Dr Hirsh diusulkan disahkan oleh pimpinan ACCP dan dilaksanakan di
AT9. solusi yang memberikan kepemimpinan dan tanggung jawab utama untuk
setiap artikel tidak ahli trombosis tetapi untuk metodologi yang, dalam hampir
semua kasus, juga adalah seorang dokter berlatih tanpa konflik penting dari
interest4,5 (Tabel 1). editor ini setiap artikel memiliki pelatihan khusus dalam
pendekatan ACCP untuk penilaian kualitas bukti dan kadar kekuatan rekomendasi
(lihat "Bukti Rangkuman" bagian). Selanjutnya, membangun kerja kelompok
pedoman sebelumnya, 6 proses menetapkan bahwa meskipun para ahli trombosis
konflik bisa terlibat dalam diskusi dan bahkan menyusun ringkasan bukti, mereka
akan dikeluarkan dari keputusan akhir mengenai kualitas dari bukti dan arah dan
kekuatan rekomendasi. konflik intelektual mendapat perhatian yang sama seperti
konflik keuangan. Pembaca pedoman dapat menemukan di suplemen data online
untuk AT9 artikel akuntansi rekomendasi-by-rekomendasi dari konflik intelektual dan
keuangan dari masing-masing anggota panel. Perubahan yang paling penting dalam
konten AT9 mengalir langsung dari perubahan ini dalam proses.
Tabel 1 -Mayor Inovasi di AT9
Lihat besar | Simpan Tabel
Ringkasan bukti
| Referensi
Keenam ACCP Konsensus Konferensi antitrombotik Therapy (AT6), 7 diterbitkan

pada tahun 2001, mengadopsi pendekatan kualitas wisatawan bukti dan kekuatan
recommendations8 yang diramalkan bahwa dari Kelas Rekomendasi, kelompok
Pengkajian, Pengembangan, dan Evaluasi (GRADE) bekerja, 9 sendiri diadopsi
dengan sedikit modifikasi untuk AT810 dan untuk semua ACCP guidelines.11 AT8,
seperti AT6 dan ACCP Konferensi Ketujuh di antitrombotik dan trombolitik Terapi:
Pedoman bukti-Based (AT7), 12 menjalani editing menyeluruh dan review kualitas
bukti, termasuk dalam banyak kasus penilaian hati-hati studi tunggal oleh editor
topik dan komite pedoman eksekutif. Namun demikian, banyak dari editor topik
tidak memiliki pelatihan methodologic atau, seperti yang terjadi di AT8, pelatihan
khusus dalam pendekatan ACCP-GRADE. Hasilnya adalah bahwa di AT8, pendekatan
ACCP-GRADE sering tidak diterapkan dengan ketelitian yang optimal, dan penulis
diproduksi sangat sedikit dari tabel ringkasan yang merupakan produk akhir ciri
khas dari proses GRADE.
Ada dua jenis tabel seperti: profil bukti dan ringkasan temuan. profil bukti
meringkas kualitas tubuh bukti untuk setiap hasil yang relevan dan, ketika bukti
berasal dari percobaan acak, termasuk presentasi penilaian pengulas 'dari risiko
bias, presisi, konsistensi, keterusterangan, dan publikasi bias.5 Pembaca AT9 bisa
menemukan profil bukti dalam suplemen data online. Teks dalam artikel AT9 utama
meliputi ringkasan lebih ringkas temuan tabel, yang meliputi penilaian kualitas
secara keseluruhan serta efek ukuran relatif dan mutlak untuk setiap hasil. Kami
tidak berhasil dalam tujuan mulia menghasilkan ringkasan tabel temuan untuk
setiap rekomendasi, tetapi pembaca akan menemukan ini untuk sebagian besar
rekomendasi utama dan berpotensi kontroversial. Pembaca akan menemukan> 10
tabel seperti di sebagian besar artikel dan> 20 dalam beberapa artikel.
Memproduksi tabel ini memaksa kekakuan berpikir dicapai dalam beberapa cara
lain. Menciptakan sejumlah besar profil bukti memberikan wawasan yang mendalam
pendekatan ACCP-GRADE untuk menilai kualitas bukti dan kekuatan rekomendasi.
Seiring dengan perekrutan GRADE-ahli editor topik, produksi profil bukti dan
ringkasan temuan tabel bertanggung jawab untuk kekakuan metodologis
peningkatan AT9.
Kami juga mencoba menerapkan pendekatan yang ketat untuk memilih format tabel
ini, sebuah isu yang telah menimbulkan kontroversi dalam kelompok kerja GRADE.
Per Olav Vandvik, Holger Schnemann, dan Nancy Santesso memimpin kelompok
dalam studi formal di mana AT9 panelis menyatakan pandangan mereka dari
presentasi optimal tables.5 yang Hasil tidak hanya dipandu presentasi profil bukti
dan ringkasan temuan di AT9 tetapi juga memberikan salah satu pilihan yang
direkomendasikan untuk kelompok kerja GRADE.
Reevaluasi Bukti
| Referensi
Mengandalkan perspektif methodologists unconflicted, ketat menerapkan
pendekatan GRADE, dan tidak termasuk orang-orang dengan konflik keuangan dan
intelektual kepentingan dari keputusan bottom-line mengenai kualitas bukti dan

kekuatan rekomendasi menyebabkan reevaluations bukti yang sudah ada
sebelumnya (Tabel 1). Misalnya, penerapan pendekatan ACCP-GRADE
membutuhkan perbedaan antara hasil pasien-penting dan pengganti. Pertama
delapan edisi pedoman antitrombotik gagal untuk sepenuhnya menyadari implikasi
dari pengganti banyak digunakan dalam uji-asimtomatik pencegahan trombosis,
trombosis screening-terdeteksi. Penggunaan pengganti ini menciptakan masalah
besar dalam membuat trade-off antara hasil pasien-penting (trombosis dan
perdarahan yang serius). Misalnya, jika ada yang tahu bahwa intervensi
meningkatkan perdarahan serius oleh 20 peristiwa di 1.000 pasien tetapi
mengurangi trombosis asimtomatik oleh 100 di 1000, apa manfaat bersih?
Membangun keuntungan bersih dalam hasil penting untuk pasien membutuhkan
mengetahui DVT simptomatik dan pengurangan emboli paru gejala diwakili oleh
penurunan 100 peristiwa tanpa gejala. Dr Hirsh dan John Eikelboom memimpin
editor topik pencegahan dalam mengembangkan pendekatan inovatif untuk
menangani masalah menyimpulkan dampak thromboprophylaxis pada trombosis
gejala dari penelitian yang mengandalkan untuk sebagian besar pada deteksi
events.13 asimtomatik Pendekatan yang tersedia, meskipun mewakili melangkah
maju, semua memiliki keterbatasan dan menyoroti kebutuhan untuk studi yang
secara langsung mengukur trombosis gejala tanpa venographic atau USG
pengawasan.
Sebagai hasil dari evaluasi ulang yang dipimpin oleh Dr Eikelboom, salah satu
konsekuensi dari pengakuan bahwa pengukuran peristiwa pasien-penting dalam
pengaturan klinis naturalistik (sebagai lawan dalam konteks skrining venographic
atau ultrasonografi untuk trombosis asimtomatik) adalah perspektif yang berbeda
pada menggunakan aspirin dalam thromboprophylaxis dalam bedah ortopedi. Para
penulis AT8 telah menyimpulkan bahwa ada bukti berkualitas tinggi membenarkan
rekomendasi kuat terhadap aspirin sebagai agen tunggal untuk thromboprophylaxis
pada pasien bedah. Penulis AT9 terfokus pada hasil dari uji coba yang sangat besar
menggunakan pengacakan tersembunyi dan menyilaukan dan mencapai dekatlengkap tindak up.14 Setelah diskusi yang lengkap dan mengulangi melibatkan
penulis semua artikel pencegahan, dan akhirnya seluruh panel, penulis AT9
menyimpulkan bahwa persidangan memberikan bukti-kualitas moderat mendukung
penggunaan aspirin, yang sekarang ditawarkan sebagai pilihan untuk
thromboprophylaxis pada pasien yang menjalani ortopedi procedures.15 penulis
AT9 utama menyimpulkan bahwa ada bukti berkualitas rendah mendukung
rekomendasi lemah penerbangan-molekul heparin berat lebih dari aspirin pada
pasien ini.
Pendekatan GRADE mendefinisikan kualitas sebagai bukti tingkat kami kepercayaan
pada perkiraan diagnostik atau pengobatan efek untuk mendukung
recommendation.16 tertentu Secara umum, perspektif berubah pada bukti
mengarah pada kesimpulan bahwa kita sering tidak bisa percaya diri dalam
perkiraan efek seperti sebelumnya diyakini. Pembaca AT9 akan sering menemukan,
karena itu, bahwa beberapa bukti dinilai sebelumnya sebagai kualitas tinggi
sekarang sedang, dan bukti dinilai sebelumnya kualitas moderat sekarang rendah.
Nilai-nilai dan Preferensi

| Referensi
iterasi serial AT9 dating kembali ke AT6 telah secara bertahap menempatkan
peningkatan penekanan pada nilai-nilai dan preferensi pasien. Untuk pertama
kalinya, panel AT7 membuat asumsi tentang nilai-nilai dan preferensi eksplisit.
Panel AT9 telah mempercepat proses itu dengan melakukan review17 sistematis
dari penelitian yang relevan dari penyelidikan empiris nilai dan preferensi pasien
tentang terapi antitrombotik. Berdasarkan review yang, AT9 panelis melakukan
latihan nilai rating yang memberikan dasar untuk nilai-nilai dan penilaian preferensi
dalam AT9, penilaian yang dirangkum di bagian pengantar dari setiap article.13 The
penilaian yang lebih eksplisit dan kuantitatif daripada pedoman sebelumnya.
Sebagai contoh, kami memperkirakan bahwa rata-rata, pasien mengalami disutilitas
GI berdarah kurang lebih sama dengan yang VTE tetapi hanya sepertiga dari
disutilitas stroke.
Diantara temuan dari tinjauan sistematis nilai pasien dan preferensi mengenai
pengobatan antitrombotik adalah heterogenitas hasil antara penelitian dan
variabilitas luas dalam nilai-nilai dan preferensi antara pasien. Karena karakteristik
inti dari rekomendasi kuat adalah keyakinan bahwa di berbagai nilai dan preferensi,
hampir semua pasien diberitahu akan membuat pilihan yang sama, variabilitas luas
dalam nilai-nilai dan preferensi pasien membuat rekomendasi yang kuat kurang
likely.18
Dampak Inovasi pada Rekomendasi
| Referensi
Pembaca AT9 akan menemukan banyak rekomendasi yang lemah mengganti
rekomendasi kuat AT8. Salah satu alasan utama untuk perubahan ini adalah
tampilan yang lebih kritis pada bukti dan kesimpulan yang dihasilkan bahwa
beberapa bukti adalah kualitas yang lebih rendah dari yang diyakini sebelumnya.
Yang kedua adalah pengakuan dari variabilitas dalam nilai-nilai dan preferensi.
Ketiga, dalam jumlah kecil rekomendasi kontroversial yang datang ke suara formal
menggunakan pemungutan suara elektronik anonim, kita diperlukan dukungan
dari> 80% dari panelis untuk membuat rekomendasi yang kuat. Akhirnya,
pengecualian ahli konflik, yang sering memiliki pendapat yang kuat tentang
pendekatan manajemen yang optimal, dari keputusan akhir mengenai kualitas bukti
dan kekuatan rekomendasi juga mungkin telah berkontribusi.
Inovasi lainnya di AT9
| Referensi
Untuk pertama kalinya, setiap panel termasuk dokter garis depan tidak terlibat
dalam riset trombosis. Tujuan dari termasuk individu-individu adalah untuk
memastikan bahwa rekomendasi dianggap realitas penuh praktek klinis seperti
yang dilihat oleh orang-orang di luar lingkungan penelitian dan untuk mendukung
upaya untuk membuat kalimat dari rekomendasi yang lebih user friendly dan
diimplementasikan.
Keterbatasan AT8 adalah pendekatan yang sangat konsisten untuk menilai risiko
perdarahan. Sam Schulman, penulis artikel resiko pendarahan di AT8,19 mengambil
tanggung jawab untuk mengembangkan pendekatan AT9 perdarahan dan
memastikan bahwa itu diterapkan secara konsisten di seluruh chapters.5
Untuk mengatasi masalah efisiensi ekonomi, kami termasuk "penggunaan konsultan
sumber daya" pada artikel panel AT9 dituduh membuat rekomendasi. Mereka
mengembangkan metodologi yang transparan dan sistematis untuk menjawab
pertanyaan yang penggunaan sumber daya mungkin mengubah arah atau kekuatan
recommendations.5
Kami membuat upaya intensif untuk menghilangkan duplikasi antara artikel dan
menyelaraskan rekomendasi antara artikel terkait. Strategi penting adalah untuk
menyertakan editor topik dan wakil editor sebagai panelis dari kedua artikel ketika
dua memiliki masalah tumpang tindih.
Akhirnya, untuk pertama kalinya, pedoman antitrombotik telah membahas masalah
diagnosis. Shannon Bates dan Romawi Jaeschke memimpin sebuah panel yang
mengambil tugas menantang menerapkan metodologi GRADE baru dikembangkan
untuk rekomendasi mengenai diagnosis DVT.20
Kesimpulan
| Referensi
Bangunan pada pekerjaan mani dari Drs Hirsh dan Dalen dan rekan-rekan mereka
selama sejarah 20-tahun dari pedoman antitrombotik ACCP, AT9 telah membuat
sejumlah perubahan dalam proses, menghasilkan perbedaan dalam pendekatan
untuk membuat rekomendasi dan konten mereka. iterasi terakhir dari pedoman ini
telah merayakan bukti berkualitas tinggi baru dan rekomendasi yang kuat bahwa
waran bukti-bukti tersebut. Wawasan dari AT9 termasuk keterbatasan bertahan
dalam kualitas bukti (khususnya yang berkaitan dengan penggunaan hasil
pengganti dalam uji profilaksis) dan kelayakan rekomendasi lemah yang
mencerminkan kurangnya kepercayaan berlaku estimasi dan variabilitas dalam
nilai-nilai dan preferensi pasien. Kami percaya bahwa tujuan, aplikasi ketat dari ilmu
pengembangan pedoman akhirnya akan melayani pasien kami.
Ucapan Terima Kasih
| Referensi
Kontribusi lainnya: Para penulis terima Rachel Gutterman, BA, dan Joe Ornelas, DC,
untuk bantuan mereka dalam mengelola proyek yang kompleks ini.
Keuangan / non keuangan pengungkapan: Singkatnya, penulis telah melaporkan ke
DADA konflik berikut menarik: Dr Crowther telah bertugas di berbagai dewan

penasihat, telah membantu dalam penyusunan materi pendidikan, dan telah duduk
di papan keamanan dan monitoring data. pihaknya telah menerima dana penelitian
dari perusahaan berikut: Leo Pharma A / S, Pfizer Inc, Boerhinger Ingelheim GmbH,
Bayer Pharmaceuticals Healthcare, Octapharm AG, CSL Behring, dan Artisan
Pharma. Total kompensasi pribadi untuk kegiatan ini selama 3 tahun terakhir total
kurang dari US $ 10.000. Dr Gutterman telah memiliki hubungan berikut yang sama
sekali tidak berhubungan dengan pedoman AT9: Presiden ACCP, GlaxoSmithKline plc
memberikan untuk belajar vasodilatasi di jaringan adiposa, National Institutes of
Health hibah untuk mempelajari dilatasi koroner manusia, dan konsultasi GE
Healthcare pada studi untuk evaluasi EKG penyakit jantung kronis. Drs Guyatt dan
Schnemann adalah co-chair dari Kelompok Kerja GRADE, dan Dr Akl adalah
anggota dan kontributor terkemuka untuk Kelompok Kerja GRADE. Dr Lewis adalah
karyawan penuh-waktu ACCP itu.
Peran sponsor: Para sponsor tidak memainkan peran dalam pengembangan
panduan ini. organisasi sponsor tidak bisa merekomendasikan panelis atau topik,
mereka juga tidak diperbolehkan akses prapublikasi ke naskah dan rekomendasi.
anggota pedoman panel, termasuk kursi, dan anggota Kesehatan & Komite
Kebijakan Sains dibutakan dengan sumber pendanaan. Rincian lebih lanjut tentang
Benturan Kepentingan Kebijakan yang tersedia secara online di http://chestnet.org.
Dukungan: pedoman ini didukung oleh Asosiasi Amerika untuk Kimia Klinik,
American College of Pharmacy Clinical, American Society of Health-System
Apoteker, American Society of Hematology, dan International Society of Thrombosis
and Hematosis.
singkatan
| Referensi
ACCP
American College of Chest Physicians
AT6
Keenam ACCP Konsensus Konferensi antitrombotik Therapy
PUKUL 7
Ketujuh Konferensi ACCP pada antitrombotik dan trombolitik Terapi: Pedoman Bukti
Berbasis
AT8
Antitrombotik dan trombolitik Terapi: American College of Chest Physicians Bukti
Berbasis Klinis Pedoman Praktik (8 Edition)
AT9
Antitrombotik Terapi dan Pencegahan Trombosis, ed 9: American College of
Pedoman Praktek Klinis Bukti Berbasis Chest Physicians
KELAS
Kelas Rekomendasi, Pengkajian, Pengembangan, dan Evaluasi

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Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians

Evidence-Based Clinical Practice Guidelines | February 2012

Introduction to the Ninth Edition:

The New Process in AT9Dealing With Conflict of Interest

Values and Preferences

Impact of Innovations on the Recommendations

Other Innovations in AT9

American College of Chest Physicians

Sixth ACCP Consensus Conference on Antithrombotic Therapy

Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based

GRADE Grades of Recommendations, Assessment, Development, and Evaluation

Abstrak | Proses Baru di AT9-Berurusan Dengan Benturan Kepentingan | Ringkasan

Keenam ACCP Konsensus Konferensi antitrombotik Therapy (AT6), 7 diterbitkan

intelektual kepentingan dari keputusan bottom-line mengenai kualitas bukti dan

Rekomendasi | Inovasi lainnya di AT9 | kesimpulan | Ucapan Terima Kasih | singkatan

DADA konflik berikut menarik: Dr Crowther telah bertugas di berbagai dewan

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