Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Abstract

Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs.The frequency, clinical characteristics and outcome of these patients have not been reported in real life.Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non‐fragile. BackgroundSubgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet.ObjectivesTo compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non‐fragile patients with VTE.MethodsRetrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg.ResultsFrom January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37‐0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10‐1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16‐2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05‐12.4), all‐cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75‐2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10‐2.85) than the non‐fragile.ConclusionsIn real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non‐fragile.

Fixed dose rivaroxaban can be used in extremes of bodyweight: A population pharmacokinetic analysis

“…[16][17][18] Conversely, outcome data for patients <50 kg are limited to a subgroup analysis of the so-called fragile patients of the EINSTEIN pooled data and observational studies. 15,19 Reflecting current practice, the Registro Informatizado Enfermedad Trombo Embólica registry has described a tendency toward traditional anticoagulation therapies in this subgroup. 19 Barsam and colleagues have previously derived a population PK model from 101 clinic patients, which suggested that bodyweight on its own was not a significant predictor of rivaroxaban PK.…”

Direct Oral Anticoagulants or Standard Anticoagulant Therapy in Fragile Patients with Venous Thromboembolism

“…2 Fragile patients are underrepresented in clinical trials, and these favorable results have not been validated yet in real life. In a recent study, we found that 42% of VTE patients in real life are fragile, 3 and that during anticoagulation they had fewer VTE recurrences and more major bleeding events than the nonfragile.…”

Special Conditions in Venous Thrombembolism – Case Series

“…There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials [1,2]. Further, design of clinical trials is challenging in some scenarios, such as in those with haemodynam-ically-unstable PE.…”