Prevention of Venous Thromboembolism. part 7

Although venography remains an important screening test for DVT, especially in evaluating the efficacy of new antithrombotic interventions, it has a number of well-recognized limitations, including the following: (1) limited availability in many medical centers; (2) questionable clinical relevance of small or distal thrombi; (3) incomplete or nondiagnostic rates of at least 20 to 40%; (4) moderate interobserver variability in its interpretation; (5) patient discomfort and risks related to the use of a contrast agent; and (6) high financial costs. Furthermore, because venography is not readily repeatable, it can only provide information about thrombosis at a single point in time rather than over a longer a time course during which clinically important VTE may arise.

Venous Doppler ultrasonography (DUS) is now the most universally accepted test for the diagnosis of lower extremity DVT, because it is highly accurate for symptomatic DVT, widely available, and noninvasive, and can be repeated. At the same time, the accuracy of DUS varies among both operators and medical centers. While DUS has reduced sensitivity for detecting DVT in asymptomatic patients, the accuracy of DUS appears to be improving. The lower sensitivity of DUS for detecting small and/or nonocclusive DVTs may even be considered advantageous, since such thrombi appear to be of doubtful clinical significance. The standardization of the DUS technique is critical in reducing the potential for the false-positive test results reported in some trials. As a result of recent improvements in DUS accuracy, an increasing number of clinical trials in thromboprophylaxis are utilizing ultrasound outcomes. We believe that DUS-positive proximal DVT is a clinically relevant finding because of the known association between proximal DVT and PE, and because patients with this finding generally receive anticoagulation therapy in routine practice.

Despite the limitations of each of these screening methods, and thus the possibility of error in the estimates of the absolute rates of DVT, the relative risk reductions (RRRs), derived from studies comparing two prophylaxis regimens are likely to be valid as long as systematic bias has been reduced through the concealed randomization of patients, caregivers, and outcome adjudicators to the study interventions received, and through the complete follow-up of patients.

1.4.2    Appropriate end points in clinical trials of thromboprophylaxis

Physicians differ widely in their views on the appropriate end points for studies of thromboprophylaxis. While some believe that contrast venography should be used as the “best” test to detect all DVTs, others argue that evidence of effectiveness should be based on a proven reduction in all-cause mortality. Both of these antithetical positions clearly have limitations.

Over the years, the majority of prophylaxis trials have used DVT, detected by sensitive screening methods, as the primary efficacy outcome.

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