Dr. Lederle and associates question our conclusion that symptomatic VTE in medical patients is reduced during treatment with prophylactic anticoagulants. We acknowledge that a discussion of these matters is important, because our findings could influence the care of many patients.

First, they indicate that Cohen and colleagues (1) did not confirm all fatal PEs with autopsy. They propose that this would overestimate the risk for such events. We included these events because, in accordance with our prespecified criteria, they were independently adjudicated as fatal PEs.

Second, they questioned our decision to extract data from only the first 21 days of follow-up in Gårdlund's study (2). We did this because, in accordance with our analysis plan, we were assessing the effect of prophylaxis during anticoagulant treatment, and prophylaxis was given for up to 21 days in Gårdlund's study. Nonetheless, we agree with their questioning the efficacy of anticoagulant prophylaxis after treatment is stopped. Indeed, we state that "the risk for VTE in patients after prophylaxis is stopped remains to be clarified and should be evaluated in future studies."

Third, they criticized our extraction of data because we counted all fatal PE events from Mahé and colleagues' study (3) but counted only "clinically relevant fatal PE" for Gårdlund's study. This was not done by choice, as Lederle and associates infer, but was based on our prespecified decision to extract primary outcome data as reported in each study. Although it would be ideal to have a standardized definition of "clinically relevant" PE, this definition does not exist. To account for the differences across studies in their methods of outcome determination, we compared outcomes within each study in an attempt to provide a consistent and nonbiased assessment of the efficacy of anticoagulants to prevent symptomatic VTE.

Although Lederle and associates state that our findings would be rendered null by a more circumspect reporting of outcomes, we disagree. We stand by our conclusion that anticoagulant prophylaxis reduces symptomatic VTE on the basis of the totality of evidence: across-study consistency of risk reduction for PE, risk reduction for symptomatic deep venous thrombosis (odds ratio, 0.47 [95% CI, 0.22 to 1.00]; P = 0.05), and supportive evidence from other studies that anticoagulant prophylaxis reduces asymptomatic deep venous thrombosis in medical patients (4).

Potential Financial Conflicts of Interest: None disclosed.