Regular Article CLINICAL TRIALS AND OBSERVATIONS Risk of venous and arterial thrombotic events in patients diagnosed with superficial vein thrombosis: a nationwide cohort study

Superficial vein thrombosis (SVT) is a relatively common condition of which the incidence was recently established to be about 0.6 per 1000 person-years (py). In the past, SVT has been considered a benign, self-limitingdisorder, requiring only symptomatic treatment. However, recent evidence showing that SVT is closely linked to occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) indicates the relevance of this condition. Three possible types of associations between SVT and DVT/PE can be distinguished. First, DVT or PE can be present concomitantly with the superficial event; this has been found in up to 29% of patients presenting with acute SVT. Second, DVT or PE can develop shortly after a patient initially presents with an isolated superficial event. In a study of 600 patientswith symptomatic SVT, but no other thromboembolic events, 18 patients (3%) developedDVTor PEwithin 3months, despitemost having received anticoagulants. Third, patientswith a history of SVT may have a fourto sixfold increased lifetime risk of DVT or PE. This close association between SVT and DVT/PE prompted the Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis with Placebo (CALISTO) trial, which showed that a 45-day anticoagulant treatment regimen after SVT is effective and safe in preventing serious thrombotic events in the 3 months after diagnosis. Two other trials have confirmed these findings. As a result, current guidelines now recommend this treatment regimen for patients with SVT of at least 5 cm in length on a lower limb. Recently, Prandoni and colleagues performed a subanalysis of CALISTO trial data to examine whether SVT is associated with increased risk of subsequent arterial cardiovascular events. The impetus for their research arose from the recently described association between venous and arterial thrombotic events. However, such a relation could not be demonstrated, with a relative risk of 0.97 for arterial cardiovascular events inSVTpatients comparedwith controls. Although the studies described here offer some insight into the risk of DVT, PE, or arterial events after a SVT diagnosis, they have limitations, such as inclusion of patients with concurrent DVT or small or selected populations (trial or specialist referral settings). We therefore set out to study the association in a large, unselected population (ie, the entire population of Denmark). The size of the study population allowed accurate estimation of absolute and relative risks as well as several subgroup analyses. Our study focused on patients with a first-time diagnosis of SVT without concurrent DVT or PE. We examined risks of subsequent DVT, PE, acute myocardial infarction (AMI), stroke, and death over different periods.