ARTICLE IN BRIEF
The third in a series of trials to determine if compression stockings reduced the risk for deep vein thrombosis (DVT) found that it did: at six months, use of intermittent pneumatic compression sleeves was associated with a 14 percent reduction in mortality and roughly a 30 percent reduction in deep vein thrombosis.
Inflatable leg sleeves designed to provide intermittent pneumatic compression reduced the occurrence of deep vein thrombosis (DVT) in recent stroke patients and improved overall survival, according to a study conducted at 94 medical centers in the United Kingdom.
At six months, use of intermittent pneumatic compression (IPC) sleeves was associated with a 14 percent reduction in mortality and roughly a 30 percent reduction in DVT, said principal investigator Martin Dennis, MD, a professor of stroke medicine at the University of Edinburgh, UK.
“The finding that treatment improved survival was unexpected and came as a complete surprise,” he told Neurology Today in a telephone interview.
“You might expect some reduction in mortality, but this was greater than we expected, suggesting that more patients might be dying from DVT or pulmonary embolism than we realize. Many deaths in the early days following a stroke are attributed to pneumonia, but the two conditions share similar symptoms,” he noted, including shortness of breath, chest pain, and lung infiltrates on chest X-ray.
The Clots in Legs Or sTockings after Stroke (CLOTS 3) trial was the third and final CLOTS trial. In the CLOTS 1 trial, the team reported that graduated compression stockings similar to flight socks did not reduce DVT risk, while the CLOTS 2 study revealed that proximal DVT occurred more often in stroke patients who wore below-knee stockings versus thigh-length stockings.
STUDY METHODOLOGY, RESULTS
The CLOTS 3 trial involved 2,876 stroke patients, half of whom were outfitted with IPC sleeves within three days of admission. Compression duplex ultrasound (CDU) of both legs was conducted at after seven to ten days, and again after 25 to 30 days when possible. Patients wore the sleeves around the clock for up to 30 days, until discharge or death.
Among 1,438 patients who wore intermittent pneumatic compression sleeves, the occurrence of DVT in the proximal veins was 3.6 percent lower than in those without sleeves (8.5 versus 12.1), while 30-day mortality was 10.8 percent compared with 13.1 percent in the untreated group; 90-day immortality was 22.3 percent versus 25.1 percent, respectively. One case of proximal DVT was prevented for every 28 patients treated, and one death was prevented for every 43, Dr. Dennis said.
The benefits were seen across all subgroups of patients, including those who suffered an ischemic or hemorrhagic stroke.
The findings, initially presented earlier this year at the European Stroke Conference in London, were published Aug. 10 in The Lancet.
Prospective studies have indicated that between 20 percent and 42 percent of stroke patients experience potentially life-threatening blood clots while immobilized after an event, according to Dr. Dennis.
“We have shown that treatment with these inflatable sleeves is feasible, safe, and an effective means of reducing venous thromboembolism (VTE) in immobilized patients in the first few days after stroke,” he said.
The inflatable sleeves, attached to a bedside electric air pump, contain air sacs that are inflated every few seconds starting at the calf and upward to the thigh. This compression mimics walking so that blood continues to flow steadily rather than pooling in the legs.
“These sleeves are now being used with patients following surgery, but this is the first time that a large randomized study has demonstrated their safety and efficacy in reducing DVT after a stroke, let alone a beneficial impact on mortality,” said Dr. Dennis.
Although blood-thinning drugs can help reduce the risk of the clots, their benefits are offset by an increased risk of bleeding complications, but there were few adverse events using IPC sleeves, he noted.
The sleeves, which cost about $20-$40, need to be replaced, on average, at least twice during a 30-day recovery period, putting the average cost per patient at around $100.
“This should be the standard of care for immobilized stroke patients. It is a fairly simple and inexpensive intervention that can have significant benefits for stroke patients.”
While the use of IPC sleeves appears to be increasing in the UK, awareness of their potential benefits appears to be lagging in the United States, Dr. Dennis said.
“I believe it is very important that more neurologists, hospitals, and stroke centers view our findings and consider using intermittent pneumatic compression with their stroke patients, especially in light of the potential survival benefits,” he said.
Philip B. Gorelick, MD, professor of translational science at Michigan State University and medical director of the Hauenstein Neuroscience Center of Saint Mary's Health Care in Grand Rapids, MI, said the findings provide a convincing argument for the use of IPC sleeves in stroke units.
“The CLOTS 3 investigators have shown a statistically significant 35 percent estimated relative risk reduction, and an absolute reduction of 3.6 percent, with intermittent pneumatic compression over non-IPC. This makes IPC therapy reasonable to recommend,” he told Neurology Today.
“In addition to the potential for reducing DVT and subsequent pulmonary embolism, which may lead to death in stroke patients, IPC devices might also increase fibrinolysis potential and have some influence on preventing remote thrombus formation in other vascular beds,” Dr. Gorelick noted.
“At a number of stroke centers where I have worked, we used intermittent pneumatic compression devices to reduce DVT risk and [related] complications. I believe the CLOTS 3 trial provides a high-level evidence base for their continued use.”
One challenge, however, is that continued application can make patients uncomfortable because leg movement is restricted, and, because the sleeves must be removed when a patient is being bathed or transported for diagnostic testing, there is an increased risk that they may not be placed back on a patient afterwards, leaving patients unprotected. The devices can also cause skin abrasion and some patients, especially older ones who are subject to skin injury, may not be well-suited for the devices, according to Dr. Gorelick.
In an accompanying editorial, Scott M. Stevens, MD, and Scott C. Woller, MD, associate professors of internal medicine at the University of Utah in Salt Lake City, noted that while venous thromboembolism is among the most significant complications associated with hospital stay, prevention measures are “persistently underused,” and much lower in medical versus surgical inpatients.
“Is it surprising that three-quarters of hospital-acquired VTEs occur in medical patients?” they asked. “To our knowledge, CLOTS 3 is the highest quality, and by far the largest, study to date of IPC use for VTE prophylaxis in non-surgical patients.”
While agreeing that IPCs can be difficult to keep on patients, they noted that less than a third of the CLOTS 3 patients achieved perfect adherence, that is, wore the sleeves for the entire length of their hospital stay. Moreover, IPC adherence was monitored by nurses and assessed three times a day, yet adherence was counted in whole days.
“This method probably yielded an incomplete picture of actual device use. Outside a trial, IPC adherence might be even worse, leading to less benefit,” they wrote, noting that future studies should examine ways to improve compliance such as technology that continually monitors IPC use.
“Nonetheless, CLOTS 3 has convinced us, and we will prescribe IPCs to patients who have had a stroke and are immobile in hospital... it could be years until similar high-quality evidence is available.”