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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: The RIETE registry has been supported by Sanofi Spain, Leo Pharma, and Rovi with an unrestricted educational grant. Dr Bikdeli reported receiving consulting fees serving as an expert on behalf of the plaintiff for litigation related to 2 specific brand models of inferior vena cava filters. Dr Krumholz reported receiving personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, F-Prime, Tesseract/4Catalyst, Martin/Baughman Law Firm, Arnold and Porter Law Firm, and Siegfried and Jensen Law Firm; being a cofounder of HugoHealth, a personal health information platform; being a cofounder of Refactor Health, an Enterprise Health Care artificial intelligence–augmented data management company; having contracts with the Centers for Medicare & Medicaid Services Association through Yale New Haven Hospital, to develop and maintain performance measures that are publicly reported; and receiving grants from Johnson & Johnson outside the submitted work. Dr Monreal reported receiving grants from Sanofi and Rovi sponsorship of the RIETE registry outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Use of Anticoagulation in Patients With Isolated Distal Deep Vein Thrombosis (IDDVT) and Patients With Proximal DVT

Figure 2.. All-Cause Death and Major Bleeding Outcomes at 90 Days

Reference group (dotted vertical line) is proximal deep vein thrombosis. Point estimates are adjusted odds ratios (aORs), with 95% CIs shown in error bars.

Figure 3.. Cumulative Incidence Rate for All-Cause Mortality and Venous Thromboembolism (VTE) Deterioration

A, All-cause mortality. B, VTE deterioration. DVT indicates deep vein thrombosis; HR, hazard ratio.

Figure 4.. All-Cause Death, Venous Thromboembolism (VTE), and Major Bleeding Outcomes at 1 Year

Reference group (dotted vertical line) is proximal deep vein thrombosis. Point estimates are adjusted hazard ratios (aHRs), with 95% CIs shown in error bars.