The risk of subsequent cancer and arterial cardiovascular events in patients with superficial vein thrombosis in the legs

Abstract

Although it has been clearly demonstrated that venous thromboembolism is associated with an increased risk of subsequent overt cancer and arterial cardiovascular events in comparison with control populations, whether this association also applies to patients with isolated (ie, without concomitant involvement of the deep vein system) superficial vein thrombosis (SVT) in the legs is unknown. In 737 consecutive patients with isolated SVT not involving the sapheno-femoral junction, we conducted a retrospective investigation to assess the rate of cancer and that of arterial cardiovascular events occurring during follow-up. The event rates were compared with those occurring in 1438 controls having comparable characteristics. Both cases and controls were followed-up for an average period of 26 ؎ 8 months (range, 3-45). Malignancy was diagnosed in 26 cases (3.5%) and 56 controls (3.9%), leading to a hazard ratio of 0.86 (95% confidence interval, 0.55%-1.35% IntroductionAlthough it has been clearly demonstrated that venous thromboembolism (VTE) is associated with an increased risk of subsequent overt cancer 1 and arterial cardiovascular disorders 2 in comparison with control populations, it is unknown whether this association also applies to patients presenting with isolated (ie, without concomitant involvement of the deep vein system) superficial vein thrombosis (SVT) in the legs. On the basis of anecdotal reports 3 and findings from case-series, 4,5 SVT is generally perceived as a marker of occult malignancy. However, a recent enquiry conducted in The Netherlands in 250 patients with spontaneous SVT and in matched control individuals identified through a search in an electronic database from a few primary health care centers failed to show an increase in the risk of cancer in patients with SVT. 6 In the recently published Calisto study, ϳ 3000 patients with isolated SVT were randomized to receive either fondaparinux or placebo for 45 days. 7 The study showed a remarkable advantage of fondaparinux over placebo for prevention of VTE events during this period. In 737 consecutive patients recruited in 32 centers that agreed to participate in this substudy, a retrospective enquiry was conducted to assess the rate of cancer and that of arterial thromboembolic events occurring after randomization. The event rates were compared with those occurring in 1438 controls having comparable characteristics recruited from the general population of northern Italy. Both cases and controls were followed-up for an average period of more than 2 years. Methods PatientsThe Calisto study recruited 3002 patients 18 years of age or older between March 2007 and May 2009 who had acute symptomatic isolated SVT of the lower extremities at least 5 cm long, as confirmed by standardized compression ultrasonography. 7 Consecutive patients recruited in each of 32 centers that agreed to participate in this substudy were eligible for the current investigation. Patients who had a history of cancer, symptomatic VTE, or symptomatic arterial cardiovascular ...

Asymptomatic deep vein thrombosis and superficial vein thrombosis in ambulatory cancer patients: impact on short-term survival

“…Whether the diagnosis of a symptomatic SVT is closely associated with occult cancer is discussed controversially. Findings from the Calisto trial suggest that patients with a SVT are not at an elevated risk to develop cancer in the following 26 months (Prandoni et al , 2011). In contrast, Sorensen et al (2012) were able to show that occurrence of SVT as well as DVT and PE is a pre-clinical marker of prevalent cancer, particularly during the first year after SVT diagnosis.…”

Risk of venous and arterial thrombotic events in patients diagnosed with superficial vein thrombosis: a nationwide cohort study

“…In their study of the risk of arterial events in 737 patients with an isolated SVT not involving the saphenofemoral junction, 13 Prandoni and colleagues found no increased risk compared with controls. In our study, we found a slightly higher risk of AMI and stroke subsequent to SVT (HR of 1.2 and 1.3, respectively).…”

“…13 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).…”

“…12 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. 13 The impetus for their research arose from the recently described association between venous and arterial thrombotic events.…”

Epidemiology of cancer-associated venous thrombosis

“…In a substudy of the Calisto trial, a trial in which ;3000 SVT patients with isolated SVT were randomized to either fondaparinux or placebo, Prandoni and coworkers compared 737 SVT patients with 1438 control patients with regard to cancer diagnoses during an average of 26 months of follow-up. 91 They concluded that occurrence of SVT in the legs does not represent a risk factor for subsequent malignancies. The same conclusion was drawn in a small study performed in the Netherlands.…”