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.
This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: guyatt@mcmaster.ca.
Gordon H
GH
Guyatt
Department of Medicine, McMaster University, Hamilton, ON, Canada.
John W
JW
Eikelboom
Keck School of Medicine, University of Southern California, Los Angeles, CA.
Michael K
MK
Gould
University of New Mexico, Albuquerque, NM.
David A
DA
Garcia
St. Joseph's Hospital, Hamilton, ON, Canada.
Mark
M
Crowther
Mayo Clinic, Rochester, MN.
M Hassan
MH
Murad
Centre for Clinical Epidemiology and Community Studies, Jewish General Hospital, Montreal, QC, Canada.
Susan R
SR
Kahn
Case and VA Medical Center, Case Western Reserve University, Cleveland, OH.
Yngve
Y
Falck-Ytter
University of Rochester, Rochester, NY.
Charles W
CW
Francis
Stanford Stroke Center, Palo Alto, CA.
Maarten G
MG
Lansberg
State University of New York at Buffalo, Buffalo, NY.
Elie A
EA
Akl
David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton, ON, Canada.
Jack
J
Hirsh
D015415:Biomarkers; D019317:Evidence-Based Medicine; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D019637:Orthopedic Procedures; D017063:Outcome Assessment, Health Care; D018579:Patient Selection; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*; D017410:Practice Guidelines as Topic; D011655:Pulmonary Embolism / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012955:Societies, Medical; D020521:Stroke / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*; D014481:United States; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control
D015415:Biomarkers; D005343:Fibrinolytic Agents