From too little to too much

Experts struggle to find the optimal venous thromboembolism prophylaxis strategy.

It turns out that giving 100% isn't always a good thing.

For the past several years, hospitals around the country have worked to maximize the percentage of inpatients given prophylaxis against venous thromboembolism (VTE). Performance measures, including those from The Joint Commission, encouraged the widespread use of pharmaceuticals to prevent clots in hospitalized medical patients.

Photo from Thinkstock
Photo from Thinkstock.

However, a growing supply of evidence indicates that near universal prophylaxis might not be benefiting patients.

Michigan researchers recently analyzed prophylaxis use and VTE rates at 35 hospitals participating in a statewide quality collaborative. The hospitals with the highest prophylaxis rates (85.8%) had just as many VTEs per patient-day in 2011 and 2012 as those with the lowest prophylaxis rates (55.5%), according to results published online Aug. 18, 2014, by JAMA Internal Medicine.

The findings supported experts' pre-existing concerns about the practice of widespread prophylaxis. In 2011, ACP put out guidelines urging physicians to only use prophylaxis after performing a risk assessment of a medical inpatient's potential for clotting and bleeding. In 2012, the American College of Chest Physicians revised its guidelines to call for risk assessment, too.

“For many years, the mantra was every hospitalized medical patient has risk factors for VTE, therefore they all need pharmacologic prophylaxis,” said Scott A. Flanders, MD, FACP, lead author of the Michigan study and director of the hospital medicine program at the University of Michigan in Ann Arbor. “I think the pendulum is swinging in the other direction.”

Obstacles remain, however, to optimizing VTE prophylaxis, including the presence of those performance measures and related hospital protocols, as well as uncertainty about the best way to complete the recommended risk assessment and the effectiveness of current prophylaxis regimens.

Current practice

It's easy to understand how universal prophylaxis against VTE came to seem like a good idea, experts said. “It's such a common clinical problem, and it's deadly,” said Amir Qaseem, MD, PhD, FACP, director of clinical policy for the College and lead author of the 2011 guidelines.

But even without the recent Michigan data, “the evidence does not support routine VTE prevention in hospitalized patients with medical illness,” said Dr. Qaseem. The group of inpatients really at significant risk of VTE is only a minority segment of the general medical population, he and other experts agree.

Another recent study found that even when VTE prophylaxis isn't given universally, it's not being targeted at high-risk patients very effectively. More than 700 cancer patients admitted to 5 academic medical centers were included in the study, published in the June 10, 2014, Journal of Clinical Oncology. About three-quarters received anticoagulation, without apparent association to their risk for clots or bleeds.

“Solid cancer patients were anticoagulated more than patients with hematologic malignancies, even though they are not at any higher risk for thrombosis. Patients admitted for cancer therapy were less likely to receive anticoagulation despite the known association between chemotherapy and deep vein thrombosis,” said lead author Jeffrey Zwicker, MD, an assistant professor of medicine at Harvard Medical School and Beth Israel Deaconess in Boston. “It seems that the majority of patients are just being put on thromboprophylaxis without assessing their need for it.”

Experts offered a number of explanations for the current misuse of prophylaxis, from pharmaceutical manufacturer marketing to fear of the serious consequences of a clot.

But a major cause may be systems actually intended to improve practice—prophylaxis measures and protocols. “If you have a performance measure or protocol in place that essentially says that you have to have done this thing regardless of a patient's underlying risk factors, now you're going to be giving prophylaxis to low-risk patients for whom the harms exceed the benefit,” Dr. Qaseem said.

The Joint Commission measures do not require prophylaxis for all medical patients, noted Michael B. Rothberg, MD, vice chair for research at the Medicine Institute at Cleveland Clinic. “But not everybody understands that,” he said. “If they document they did a risk assessment and the patient doesn't qualify, then they're fine, they met the quality measure.”

In some systems, ordering prophylaxis may be an easier way to fulfill the requirement than documenting why you didn't order it. “If you put them on prophylaxis, you don't even have to show you did a risk assessment. There's no penalty for treating someone who doesn't need it,” said Dr. Rothberg.

That problem could be fixed, the experts noted. “We need performance measures that account for risk assessment prior to giving prophylaxis,” said Dr. Qaseem.

Dr. Rothberg went a step farther. “I'd like to see quality measures [in which] . . . you're penalized if you don't treat high-risk people and you're penalized if you do treat low-risk people, or if you treat people who are at high risk for bleeding,” he said.

Risk assessment options

First, however, there needs to be a general agreement about how to assess for the risk factors. “The evidence is insufficient to recommend a validated tool,” said Dr. Qaseem.

“There are a lot of risk assessment rules out there,” said Dr. Flanders. “The American College of Chest Physicians endorsed the PADUA scoring system, but that was developed in a very small number of patients. There's the Caprini scoring system, there's the IMPROVE model, there's the Intermountain Health model.”

The ACP guidelines noted that many tools are available but did not recommend any in particular. Dr. Flanders has studied the accuracy of the various risk assessment models using the Michigan data. “Unfortunately, none of them are perfect. None of them really have outstanding discriminatory capabilities of identifying patients who should get [prophylaxis],” he said.

One limitation of the assessment tools is that the patients used to develop them have some significant differences from the patients seen by hospitalists today. “The original trials, conducted over 15 years ago, had an average hospital length of stay of about 7 to 10 to 12 days,” said Alex C. Spyropoulos, MD, FACP, director of anticoagulation services and clinical thrombosis at Lenox Hill Hospital in New York.

The patients were not only in the hospital longer but also in bed longer. “People aren't immobilized for as long as they used to be, and that's why most people are at pretty low risk,” said Dr. Rothberg.

He has also studied the accuracy of the risk assessments in contemporary medical inpatients. “In the PADUA [evidence], the patients sort of split nicely into those who have a risk of 0.4% and people who have a risk of 11%, so that's a really nice dividing line,” said Dr. Rothberg. “We haven't been able to get such a huge separation . . . . We got patients from really low risk, like 0.1% all the way up to about 2%, but 2% was about the maximum risk that we could find.”

That finding confirms Dr. Qaseem's perspective on the tools. “Most of these VTE prophylaxis studies are done in high-risk populations. You cannot necessarily extrapolate the results to medium- or low-risk populations,” he said.

Researchers are working hard to improve the assessments and to make them easier for physicians to use. “Once we've come up with the risk prediction model, we're going to automate it in the electronic health record, so the physicians won't have to go looking for it, and they won't have to enter the information themselves,” said Dr. Rothberg.

Dr. Spyropoulos, who is one of the authors of the IMPROVE scoring system (which includes assessments for both clot and bleeding risk), is working in a similar direction. “If I had my magic wand, I'd have an app, and I'd see which patients will have a threshold IMPROVE VTE score and which won't have an IMPROVE bleed score, and then I would prophylax those patients,” he said. Even without magic, such a tool should be available in 2 to 3 years, he predicted.

Failure to prevent

After they've figured out risk assessment, the VTE prevention experts will have to tackle the next challenge—actually preventing VTEs in the high-risk patients. Not only did the Michigan study find that VTE prophylaxis on a hospital level failed to reduce VTEs, but it also showed that most of the patients who had VTEs had received prophylaxis.

“They were given what they should have been given, yet they developed blood clots anyway. Even if we identify patients that appear to be at particularly high risk, our current strategies are not preventing a lot of VTEs,” said Dr. Flanders.

There are 2 most likely solutions to this problem, according to the experts—giving more prophylaxis and giving it for longer. Remember those patients in the early research who stayed in the hospital for 10 days? Those longer stays meant more days of prophylaxis as well as higher VTE risk.

“Hospital-based thromboprophylactic regimes are failing simply because of inadequate duration,” said Dr. Spyropoulos.

Researchers are investigating this issue. “There have been studies that suggest that extending the use of these medications once patients leave the hospital does further reduce the risk of VTE but comes with an increased bleeding risk, so no net benefit,” said Dr. Flanders. “There are some studies ongoing now that seek to specifically try to identify a particularly high-risk subset.”

That high-risk subset, or a similar one, would also be the target of any higher-dose anticoagulation regimen, which is a possible future direction for VTE prophylaxis. “Before that becomes a safe strategy, we're going to want better tools to identify which group that is, because the risk of bleeding with intensive anticoagulation then becomes more significant,” said Dr. Flanders.

Until those improved tools are available and new recommendations are made, hospitalists should try to make the best of what they have, experts agreed. “It's better to use something than to use nothing,” said Dr. Rothberg of the risk prediction tools.

Systems and judgment

In addition to a tool of choice, hospitals should have a system for prophylaxis, and it should be one that instigates assessment rather than making an order for prophylactic medication the default.

“Have some type of protocol in place,” said Dr. Spyropoulos. “Either some kind of electronic alert or . . . I've seen institutions do wonders with a simple paper or a warm human body that is knowledgeable about this, like a pharmacist or a nurse.”

There should also be a system for reassessing risk of VTE during a hospitalization, suggested Dr. Flanders. “If a patient goes to the intensive care unit, if they have a central line placed, if their length of stay exceeds 5 days, their risk of VTE begins to go up. Even if they were felt to be low risk when they first came into the hospital and did not need pharmacologic prophylaxis, 1 week into a hospitalization, they may all of a sudden be high risk,” he said.

In general, be thoughtful about prophylaxis choices, even if you have automated prompts and tools to help you make them, advised Dr. Qaseem. “Of course, these instruments help in making decisions about who should be getting heparin prophylaxis, but ultimately, a lot of it is dependent on clinical judgment . . . Clinical evaluation is still incredibly important in making these decisions,” he said.

In the decision process, remember the risks on both sides of the choice. “There's some fear of what if the patient has a VTE and they didn't get prophylaxis. But not so many people think about what if the patient bleeds after they got prophylaxis,” said Dr. Rothberg. “Treat each person as an individual, and take this seriously.”