THROMBOSIS AND HEMOSTASIS Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study

To test recommended anticoagulation measures as predictors of 180-day venous thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents with incident VTE over the 14-year period of 1984-1997, and followed each case (N 1166) forward in time for VTE recurrence. We tested the activated partial thromboplastin time (APTT), international normalized ratio (INR), and other measures of heparin and warfarin anticoagulation as predictors of VTE recurrence while controlling for baseline and timedependent characteristics using Cox proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients received heparin and warfarin, respectively, and 85 (8%) developed VTE recurrence. In multivariable analyses, increasing proportions of time on heparin with an APTT > 0.2 anti-Xa U/mL and on warfarin with an INR > 2.0 were associated with significant reductions in VTE recurrence, while the hazard with active cancer was significantly increased. Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement were not independent predictors of recurrence. At a heparin dose > 30 000 U/d, the median proportion of time with an APTT > 0.2 anti-Xa U/mL was 92%, suggesting that routine APTT monitoring and heparin dose adjustment may be unnecessary. In summary, lower-intensity heparin and standardintensity warfarin anticoagulation are effective in preventing VTE recurrence. (Blood. 2011;118(18):4992-4999)