Predictors of Recurrent Venous Thromboembolism after Pulmonary Embolism in Korea

Abstract

To identify risk factors for index venous thromboembolism (VTE) patients is important to estimate the recurrence rate of VTE after discontinuing treatment and to decide how long anticoagulation therapy should continue for patients. Extended treatment after at least 3 months of anticoagulation depends on patient-specific factors and laboratory test results, including antiphospholipid antibodies. The recurrence rates after discontinuing anticoagulation in patients with pulmonary embolism (PE) having transient risk factors and in those with PE without cancer, known thrombophilia, or any transient risk factor were ~2.5% and 4.5% per year, respectively. In a population-based case-cohort study performed with patients having VTE, the overall 5-year recurrence rate was 24.5%, whereas the rates were 43.4%, 27.3%, and 18.1% in cancer-associated, idiopathic, and non-cancer secondary cases, respectively. The suggested high risks of recurrence of >8% per year were observed in cases with active cancer, one or more previous episodes of VTE in the absence of a major transient or reversible factor, and antiphospholipid antibody syndrome (APS). The poor quality control of vitamin K antagonist is a risk factor for recurrent VTE. In a prospective warfarin management study, patients with first acute unprovoked VTE episode were managed with international normalized ratio (INR) and followed up 21 months for recurrence. The relative risk (RR) of recurrence in patients who stayed more time at INR values <1.5 in the first 90 days was 2.70 (95% confidence interval [CI], 1.39–5.25). To evaluate the effect of preceding length of vitamin K antagonist treatment and VTE recurrence after discontinuing treatment, a pooled analysis of data from seven randomized trials was performed. The hazard ratio (HR) for recurrence in patients with interruption in 1 month or 1.5 months compared with that in 3 months was 1.52 (95% CI, 1.14–2.02). However, HR in 3 months compared with that in 6 months was 1.19 (95% CI, 0.86–1.65). Shorter durations of anticoagulation were related to higher rates of VTE recurrence. With respect to patients’ sex, the recurrence rate of VTE after discontinuing treatment was higher in men than in women. In a meta-analysis, RR in men compared with that in women was 1.6 (95% CI, 1.2–2.0). In a patient-level meta-analysis, the HR for recurrence in men compared with that in women was 1.8 (95% CI, 1.4–2.5). After adjustment for hormone-associated VTE, the risk of recurrence in men was 2.2-fold higher than that in women. In a retrospective cohort study performed in Korea, the recurrence rate in men was 1.8-fold (95% CI, 0.8–4.1) higher than that in women. Studies revealed no relationship between excessive body weight of patients and recurrence of VTE. In a prospective cohort study, 4 years after discontinuing treatment, the recurrence rates of VTE in patients with normal weight, overweight, and obesity were 9.3% (95% CI, 6.0–12.7), 16.7% (95% CI, 11.0–22.3), and 17.5% (95% CI, 13.0–22.0), respectively. As a result, excess of body weight is reported as a risk factor for recurrent VTE. Contrary to this study, in the Multiple Environmental and Genetic Assessment follow-up study, the adjusted HR of recurrent VTE in overweight or obese patients and that in normal body weight patients were 1.05 (95% CI, 0.88–1.27) and 0.94 (95% CI, 0.74–1.19), respectively. In a multicenter prospective cohort study of patients with elderly VTE, HRs for body mass index (BMI) and waist circumference on rePredictors of Recurrent Venous Thromboembolism after Pulmonary Embolism in Korea