Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Clinical course and treatment of incidentally detected splanchnic vein thrombosis: an individual patient data meta-analysis.

BACKGROUND: The clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined. OBJECTIVES: The objectives of this study were to evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess the safety and effectiveness of anticoagulant treatment in incidental SVT. METHODS: Individual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality. The safety outcome was major bleeding. Incidence rate ratios and 95% CIs for incidental vs symptomatic SVT were estimated before and after propensity-score matching. Multivariable Cox models were used considering anticoagulant treatment as a time-varying covariate. RESULTS: In total, 493 patients with incidental SVT and 493 propensity-matched patients with symptomatic SVT were analyzed. Patients with incidental SVT were less likely to receive anticoagulant treatment (72.4% vs 83.6%). Incidence rate ratios (95% CI) for major bleeding, recurrent VTE, and all-cause mortality in patients with incidental SVT compared with symptomatic SVT were 1.3 (0.8, 2.2), 2.0 (1.2, 3.3), and 0.5 (0.4, 0.7), respectively. In patients with incidental SVT, anticoagulant therapy was associated with a lower risk of major bleeding (hazard ratio [HR] 0.41; 95% CI, 0.21 to 0.71), recurrent VTE (HR 0.33; 95% CI, 0.18 to 0.61), and all-cause mortality (HR 0.23; 95% CI, 0.15 to 0.35). CONCLUSION: Patients with incidental SVT appeared to have a similar risk of major bleeding, a higher risk of recurrent thrombosis, but lower all-cause mortality than patients with symptomatic SVT. Anticoagulant therapy seemed safe and effective in patients with incidental SVT.

Clinical Presentation and Short- and Long-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis vs Proximal Deep Vein Thrombosis in the RIETE Registry.

Importance: Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE). Objective: To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT. Design, Setting, and Participants: This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection. Main Outcomes and Measures: Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE. Results: A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%). Conclusions and Relevance: Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

Changing trends in inferior vena cava filter indication for venous thromboembolism over the last two decades: a retrospective observational study.

BACKGROUND: The present study aimed to evaluate changes in the incidence, patients' profile and indications of inferior vena cava filters at a single center over the past two decades. METHODS: We retrospectively analyzed 187 consecutive patients with a venous thromboembolism requiring a filter at a tertiary hospital between 1999-2018. Within this period the availability of retrievable filters (since 2007) and the withdrawal of filter indication for recurrent venous thromboembolism from guidelines (since 2008) may have contributed to change practice patterns. Patients' profile, filter indication and survival were compared between decades (1999-2008 vs. 2009-2018). RESULTS: The filter insertion rate doubled (60 vs. 127 cases) over 2009-2018. In this later period there was an unexpected rise (15 vs. 68 cases, P<0.001) of patients with isolated pulmonary embolism as baseline venous thromboembolism episode, without other relevant changes in patients' profile or survival. Regarding indications, there was an increase in filters for bleeding risk (23 vs. 45) and a reduction for venous thromboembolism recurrence (20 vs. 7), but also an unexpected increase of cases for bleeding (15 vs. 72). Among the 116 retrievable filters indicated for a temporary cause, 70 (60.3%) were finally not removed, being persistence of filter indication (n=33, 47.1%) the most common cause. CONCLUSIONS: The number of filters inserted at our institution has raised over the last two decades. This increase was partly unexpected and perhaps related to the availability of retrievable filters. Unfortunately these devices remain frequently non-removed being persistence of the indication the most frequent cause.

Correction to: Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism.

In the original publication, part of the conflict of statement was incorrectly published as "Dr. Bikdeli reports that he was approached by lawyers on behalf of plaintiffs in litigation related to IVC filters". The correct statement should read as "Dr. Bikdeli reports that he is a consulting expert (on behalf of the plaintiff) for litigation related to a specific type of IVC filters".

Venous thromboembolism in young adults: Findings from the RIETE registry.

BACKGROUND: Little is known on the clinical characteristics, risk factors and outcomes during anticoagulation in young patients with acute venous thromboembolism (VTE). METHODS: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to assess the clinical characteristics, risk factors and outcomes during anticoagulation in VTE patients aged 10-24 years. Data were separately analyzed according to initial presentation and gender. RESULTS: Of 76,719 patients with VTE, 1571 (2.0%) were aged 10-24 years. Of these, 989 (63%) were women and 669 (43%) presented with pulmonary embolism (PE). Most women were using estrogens (680, 69%) or were pregnant (101, 10%), while 59% of men had unprovoked VTE. Women were more likely to present with PE (48% vs. 34%). The majority (87%) of PE patients had Sat O2 levels ≥90% at baseline. The vast majority (97%) of PE patients were at low risk according to the PESI score, many (90%) at very low risk. During the course of anticoagulation (median, 192 days), 40 patients had VTE recurrences, 17 had major bleeding and 10 died (3 died of PE). Women had as many VTE recurrences as major bleeds (15 vs. 14 events), while men had many more VTE recurrences than major bleeding (25 vs. 3 events). CONCLUSIONS: VTE is associated with low risk of short-term mortality in young adults. Noticeable gender differences exist in the risk factor profile and the risk of VTE recurrences and major bleeding in the course of anticoagulation.

Correction to: Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism.

In the original publication, part of conflict of statement was incorrectly published.

Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism.

The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3 months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3 months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2 days) and at lower doses (95 ± 52 IU/kg/day vs. 104 ± 55 of low-molecular-weight heparin) than those not receiving a filter. During the first 30 days after bleeding (after excluding 246 patients who died within the first 24 h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n = 122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n = 429). In VTE patients experiencing major bleeding during the first 3 months, use of an IVC filter was associated with reduced mortality rates.Clinical Trial Registration NCT02832245.

Outcomes Associated With Inferior Vena Cava Filters Among Patients With Thromboembolic Recurrence During Anticoagulant Therapy.

OBJECTIVES: The aim of this study was to assess the effectiveness of inferior vena cava (IVC) filter use among patients who develop recurrent symptomatic venous thromboembolism (VTE) on anticoagulant therapy. BACKGROUND: There is a lack of efficacy evidence of IVC filter therapy in patients with VTE recurrence on anticoagulant therapy. METHODS: In this cohort study of patients with acute VTE identified from the RIETE (Registro Informatizado de la Enfermedad Tromboembólica) registry, the associations between IVC filter placement for VTE recurrence in the first 3 months of anticoagulant therapy and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, second recurrent VTE, and major bleeding rates through 30 days after diagnosis of recurrence were assessed. RESULTS: Among 17 patients treated with filters and 49 matched patients treated without filters for VTE recurrence that presented as deep vein thrombosis, propensity score-matched groups showed no significant differences in death for filter insertion compared with no insertion (17.7% vs. 12.2%; p = 0.56). Among 48 patients treated with filters and 91 matched patients treated without filters for VTE recurrence that presented as PE, propensity score-matched groups showed a significant decrease in all-cause death for filter insertion compared with no insertion (2.1% vs. 25.3%; p = 0.02). The PE-related mortality rate was not significantly lower for filter insertion than no insertion (2.1% vs. 17.6%; p = 0.08), though the point estimates markedly differed. CONCLUSIONS: Among patients with VTE recurrence during the first 3 months of anticoagulant therapy, IVC filter insertion was not associated with a survival benefit in patients who recurred with deep vein thrombosis, although it was associated with a lower risk for all-cause death in patients who recurred with PE.