ALBERT

Description: Introduction Patients with a second venous thromboembolism (VTE) generally receive anticoagulant treatment for indefinite duration, although it is known that the recurrence risk diminishes over time while the risk of hemorrhage persists with continued anticoagulation and increases with age. Based on these arguments and the limited evidence for indefinite duration of treatment, the Dutch guideline recommends to consider limited duration of treatment (i.e. 12-month) for a 'late' second VTE, defined as a second VTE diagnosis 〉1 year after discontinuing treatment for a first VTE. It is hypothesized that the risk of continued anticoagulation might outweigh the benefits in those patients. We evaluated this management in daily practice. Methods Since 2003, a limited duration of treatment was systematically considered in consecutive patients with a late second VTE at a single academic hospital in The Netherlands. Incidence rates and cumulative incidence rates for a third VTE were calculated in patients who were treated for a limited duration and for an indefinite duration separately. For patients who were treated for a limited duration, hazard ratios (HR) for a third VTE were calculated for unprovoked versus provoked second VTE and DVT or PE as second VTE diagnosis. HR were adjusted for age, sex and where possible for type of second VTE and whether the second VTE was provoked or unprovoked. Results Of 132 patients with a late second VTE, 77 patients were treated for limited duration, of whom 26 developed a symptomatic third VTE after treatment cessation during a cumulative follow-up of 277 years, resulting in an incidence rate of 9.4/100 patient-years (95%CI 6.1-14). Cumulative incidence rates were 15% (95%CI 6.1-14) and 33% (95%CI 18-49) after 1 and 5 years of follow-up (Figure 1). In patients who were treated for an indefinite duration, the incidence rate was 1.2/100 patient-years (95%CI 0.33-3.1). The incidence rates in patients with an unprovoked VTE and a VTE related to a transient provoking factor were 12 per 100 patient-years (95%CI 7.4-19) and 5.6 per 100 patient-years (95%CI 2.2-12) respectively with a HR of 2.8 (95%CI 1.1-7.2) (Figure 2). No difference was observed for patients with deep vein thrombosis as second VTE compared to patients with pulmonary embolism as second VTE, HR 0.65 (95%CI 0.29-1.5). Conclusion The incidence rate of 9.5/100 patient-years for a third VTE after a limited duration of treatment for a second VTE largely exceeds the risk of major hemorrhage associated with long-term anticoagulant treatment, which has been estimated to be 2.7/100 patient-years. Therefore, these findings strongly suggest that identifying patients with a relatively low recurrence risk based on the interval between first and second VTE is not an appropriate strategy. Only in patients with a second VTE in the presence of a transient provoking factor the recurrence risk approaches the risk of major bleeding associated with long-term anticoagulant treatment and a limited duration of treatmentmay still be considered in these patients. Follow-up started at the time of the second venous thromboembolism diagnosis for both categories. Figure 1: Figure 1:. Cumulative incidence rate of a third venous thromboembolism in patients treated for a limited duration and patients treated for an indefinite duration. Note: nrVTE: number of recurrent VTE; PAR: patients at risk Follow-up started at the time of cessation anticoagulant treatment. Figure 2: Figure 2:. Cumulative third venous thromboembolism event rate in patients with a provoked second VTE versus an unprovoked second VTE, treated for a maximum of 12 months. Note: nrVTE: number of recurrent VTE; PAR: patients at risk Disclosures No relevant conflicts of interest to declare.

Description: Introduction Incidental pulmonary embolism (IPE) is defined as a pulmonary embolism diagnosed on a CT-scan performed for reasons other than a clinical suspicion of PE. Generally identified on staging scans, IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. In order to determine the outcome more accurately, and to identify clinical characteristics related to the prognosis, we pooled individual patient data from eleven observational studies and ongoing registries. Methods A systematic literature search aiming to identify studies reporting on patients diagnosed with cancer-associated IPE was performed. Authors of selected studies were invited to participate. Incidence rates of objectively diagnosed symptomatic recurrent venous thromboembolism (VTE), major bleeding and mortality during 6-month follow-up were pooled. Individual patient data was collected to perform subgroup analyses, for which all patients were considered as one cohort. Hazard ratios (HR) were adjusted for age, sex and cancer stage. Results Individual patient data of 926 cancer patients with IPE from 11 observational studies and ongoing registries were included (Table 1). The overall pooled 6-month risk of symptomatic recurrent VTE was 5.8% (95%CI 3.7-8.3), of major bleeding 4.7% (95%CI 3.0-6.8) and of mortality 37% (95%CI 28-47). The VTE recurrence risk was comparable in patients treated with VKA and LMWH with incidence rates of 6.4% (95%CI 2.2-12) and 6.2% (95%CI 3.5-9.6), HR 0.89 (95%CI 0.27-2.9). In contrast, this incidence rate was 12% (95%CI 4.7-23) in patients who were left untreated, HR 2.9 (95%CI 0.65-13; Figure 1). The risk of major bleeding was significantly higher in patients treated with VKA compared to those treated with LMWH, 13% (95%CI 6.4-20) versus 3.9% (95%CI 2.3-5.9), HR of 3.2 (95%CI 1.4-7.4) (Figure 2). The 6-month mortality was 37% (95%CI 29-44) in patients treated with LMWH, 28% (95%CI 18-40) in those treated with VKA and 47% (95%CI 28-66) amongst untreated patients. The all-cause mortality at 6 months was significantly higher for patients with a central thrombus (either central or lobar) compared to those with a more peripheral IPE (either segmental or subsegmental); 42% (95%CI 33-52) versus 30% (95%CI 25-36, HR 1.8 (95%CI 1.4-2.3). Conclusions The most important finding of this study is the 12% 6-month risk of symptomatic recurrent VTE in patients with cancer-associated IPE who did not receive anticoagulant treatment, which is more than double the risk of patients who were anticoagulated. These numbers recall the effect size of anticoagulants used in symptomatic PE and support the judicious initiation of anticoagulant treatment in cancer-associated IPE. The association between more centrally-located thrombi and mortality following IPE is a new finding that parallels outcomes for symptomatic PE, and one which may further support similar management. Regarding the choice of anticoagulant, VKA were associated with a significantly higher risk of major bleeding than LMWH, with a comparable risk of recurrent VTE. The findings of this observational study should be preferably confirmed in a randomized trial. Figure 1: Figure 1:. The 6-month risk of recurrent venous thromboembolism related to anticoagulant treatment. Figure 2: The 6-month risk of major bleeding related to anticoagulant treatment. Figure 2:. The 6-month risk of major bleeding related to anticoagulant treatment. Abstract 590. Table 1: Baseline characteristics Treatment All patients n=926 (100%) LMWH n=732 (79%) VKA n=100 (11%) No treatment n=53 (6%) Other treatment n=41 (4%) Mean age (SD) 65 (12) 64 (12) 68 (12) 65 (14) 68 (13) Male sex, n (%) 491 (53) 378 (52) 60 (60) 31 (58) 22 (54) Cancer stage, n (%) Metastatic 501 (54) 400 (55) 56 (56) 33 (62) 12 (29) Non-metastatic 192 (21) 143 (20) 34 (34) 12 (23) 3 (7.3) Unspecified 233 (25) 189 (26) 10 (10) 8 (15) 26 (63) Cancer type, n (%) Lung 176 (19) 135 (18) 16 (16) 18 (34) 7 (17) Colorectal 185 (20) 150 (20) 20 (20) 9 (17) 6 (15) Other gastrointestinal 187 (20) 147 (20) 15 (15) 13 (25) 12 (29) Breast 65 (7.0) 52 (7.1) 10 (10) 1 (1.9) 2 (4.9) Gynaecological 64 (6.9) 56 (7.7) 5 (5.0) 0 (0) 3 (7.3) Other 206 (22) 155 (21) 31 (31) 10 (19) 10 (24) Haematological 43 (4.6) 37 (5.1) 3 (3.0) 2 (3.8) 1 (2.4) Largest artery involved, n (%) Central 292 (32) 230 (31) 30 (30) 11 (21) 21 (51) Peripheral 495 (53) 395 (54) 62 (62) 29 (55) 9 (22) Unspecified 139 (15) 107 (15) 8 (8.0) 13 (25) 11 (27) Disclosures No relevant conflicts of interest to declare.