Predictors of Venous Thromboembolism Recurrence, Adjusted for Treatments and Interim Exposures: A Population-based Case-cohort Study

Background Predictors of venous thromboembolism (VTE) recurrence are uncertain. Objective To identify predictors of VTE recurrence, adjusted for treatments and interim exposures. Materials and Methods Using Rochester Epidemiology Project resources, all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988-2000, who survived 1 day were followed for first objectively-diagnosed VTE recurrence. For all patients with recurrence, and a random sample of all surviving incident VTE patients (n = 415), we collected demographic and baseline characteristics, treatments and interim exposures. In a case-cohort study design, demographic, baseline, treatment and interim exposure characteristics were tested as potential predictors of VTE recurrence using time-dependent Cox proportional hazards modeling. Results Among 1262 incident VTE patients, 306 developed recurrence over 6,440 person-years. Five-year recurrence rates, overall and for cancer-associated, idiopathic and non-cancer secondary VTE, were 24.5%, 43.4%, 27.3% and 18.1%, respectively. In multivariable analysis, interim hospitalization, active cancer, pregnancy, central venous catheter and respiratory infection were associated with increased hazards of recurrence, and warfarin and aspirin were associated with reduced hazards. Adjusting for treatments and these interim risk factors, male sex, baseline active cancer and failure to achieve a therapeutic aPTT in the first 24 hours were independently associated with increased hazards of VTE recurrence over the entire follow-up period, while the hazards of recurrence for patient age, chronic lung disease, leg paresis, prior superficial vein thrombosis and idiopathic VTE varied over the follow-up period. Conclusions Baseline and interim exposures can stratify VTE recurrence risk and may be useful for directing secondary prophylaxis.