Elastic compression stockings (ECSs) and intermittent pneumatic compression (IPC) devices have been used in a variety of medical settings, usually with the goal of restoring or maintaining normal venous return from the legs. Two recent publications provide important evidence about the effectiveness of these modalities in two different settings.
The first study was a double-blinded, randomized, controlled trial of graduated ECSs (30 to 40 mm Hg at the ankle) versus placebo stockings (< 5 mm Hg compression at the ankle). The trial was designed to test the hypothesis that ECSs reduce the risk of post-thrombotic syndrome (PTS), a chronic complication of arm or leg deep-vein thrombosis (DVT). At 24 different North American centers, the “SOX” investigators enrolled 806 patients (mean age 55 years; 60% men) with a first, proximal leg DVT. Patients were included only if they 1) had a life expectancy > 6 months, 2) did not receive up-front thrombolytic therapy, and 3) had no contraindication to compression stockings. One year after randomization, the proportion of patients with PTS (as defined by validated, prespecified scoring systems) was 14 percent in the ECS arm and 13 percent in the “placebo stockings” arm. Similarly, overall quality of life (as measured by the SF-36 questionnaire) was not statistically different between the two groups.
The second study was an unblinded, primary, VTE prevention trial, involving 2,876 patients (mean age 75 years, 52% women) from 105 hospitals in the United Kingdom who were both hospitalized for acute stroke (ischemic or hemorrhagic) and immobile. Patients in the CLOTS 3 trial were randomly assigned to receive either bilateral thigh-length IPC (n=1438) or no IPC (n=1438). Individuals with subarachnoid hemorrhage or leg problems (e.g., skin ulcers or severe edema) were excluded. Sequential compression was continued in the intervention group for 30 days or until the patient became independently mobile, was discharged, declined further use, or had adverse effects. All outcomes were evaluated 30 days after enrollment. The primary outcome (symptomatic or asymptomatic proximal DVT) occurred less commonly in the group assigned to IPC (9.6% vs. 14%; p=0.001). Symptomatic DVT, a key secondary endpoint, also occurred less frequently in the intervention group (4.6% vs. 6.3%; p=0.045). The rate of pulmonary embolism was not statistically different between the groups, but the numeric trend favored IPC (2.0% vs. 2.4%; p=0.453). IPC increased skin breaks (3.1% vs 1.4%, p=0.002). A strong, but statistically non-significant, trend toward lower 30-day mortality favored the IPC group (22% vs. 25%, p=0.057).
In Brief
Much can be learned from these two important prospective trials. The SOX trial is probably practice-changing. Until now, VTE experts have recommended that most patients with proximal leg DVT wear ECSs (30 - 40 mm Hg at the ankles) because two previous studies1,2 had indicated that ECS use could decrease the risk of PTS by 50 percent. However, neither of these often cited studies was blinded. The PTS score, which is the key outcome measure of all these trials, depends heavily on subjective assessments by both clinicians and patients; thus the possibility of bias in unblinded comparisons is significant. By using “placebo” stockings in the comparator arm, the SOX investigators eliminated this kind of bias and found no benefit from ECSs. More evidence is needed about how we might reduce the risk of PTS before it occurs. While ECSs may still be worth trying as a palliative measure in the 10 to 15 percent of patients who develop moderate to severe PTS, the SOX trial suggests we will need to look beyond ECSs if we hope to prevent PTS in the first place.
The CLOTS-3 trial is by far the largest and most rigorously designed study that shows that IPC devices can substantially reduce the risk of VTE in a non-surgical population of hospitalized patients. Hematologists are often asked to comment on the risks and benefits of VTE prevention. For some populations (e.g., patients admitted for acute leukemia or hematopoietic cell transplantation), pharmacologic modalities not only are costly but also probably carry a non-trivial risk of bleeding. The CLOTS-3 study, along with a recent meta-analysis,3 provides high-quality evidence that IPC, when properly applied, can provide substantial protection against VTE.
References
Competing Interests
Dr. Garcia indicated no relevant conflicts of interest.
