Which patients to anticoagulate and how

Updated guidelines, new drugs are among the things to know to treat venous thromboembolism.

Pulmonary embolism (PE) is a bigger problem than many hospitalists realize, according to Steven Deitelzweig, MD, MMM, FACP. “In fact, up to 10% of all inpatient deaths in the U.S. today come as a result of PE, and PE is often not recognized, often off the radar screen,” he told attendees at the Internal Medicine Meeting 2017 precourse on hospital medicine.

His own research, published in the American Journal of Hematology in 2011, shows that venous thromboembolism (VTE) as a whole is on the rise, a trend that's expected to continue. “When we modeled this out to 2050, it was more than a doubling that's being anticipated,” said Dr. Deitelzweig, who is system chair of hospital medicine for Ochsner Health System in New Orleans.

To help their patients avoid becoming part of this statistic, hospitalists have guidelines from the American College of Chest Physicians and practical guidance from the Anticoagulation Forum. The guidelines are frequently updated, with the most recent version coming out in 2016, but they are not totally definitive, according to Dr. Deitelzweig.

“There's not one 1A recommendation in the entire compendium any longer,” he said. “What that means to us as practicing clinicians, hospitalists, is that we have a lot more latitude in how best we think these patients need to be managed.”

There are also a lot more treatment options than there were seven years ago, when the drugs initially known as novel oral anticoagulants first came out. “They're not so novel any longer, are they?” Dr. Deitelzweig said. Given that, most in the field now call them direct oral anticoagulants, or DOACs. “That's been endorsed by the International Society on Thrombosis and Haemostasis,” he said. He also told physicians to expect yet another DOAC option, betrixabanto, to receive FDA approval in the near future.

The DOACs represented one of the most significant changes in the latest update of the guidelines. They were recommended over warfarin for therapy of patients with deep venous thrombosis or PE, as long as they don't have active cancer.

“That's because extended treatment with the DOACs reduces repeat VTE and is associated with less bleeding risk,” Dr. Deitelzweig said. “It's important to recognize there is not one DOAC preferred over another DOAC in the guidelines.”

Physicians should also recognize which patients are suited to DOAC therapy. “Your patient must be adherent,” said Dr. Deitelzweig, noting that the half-life of warfarin is 40 hours, compared to 12 hours with a DOAC. “What happens if you miss a day of warfarin? Nothing,” he said. “What happens if you miss a day of a DOAC? Everything. They're no longer anticoagulated.”

DOACs are good for patients whose international normalized ratios (INRs) are often out of the therapeutic range on warfarin. Good INR control involves being in the therapeutic range more than 60% of the time, so patients with less control than that might be better off on a DOAC, he said.

To take a DOAC, patients should also have good renal and hepatic function. “If you look at all the clinical trials [of DOACs] in aggregate, you know how many patients were enrolled on both the arterial and venous side who had a creatinine clearance less than 25 [mL/min]?” Dr. Deitelzweig asked. “Zero. Not a one.” He recommended caution about these drugs in patients with a creatinine clearance less than 50 mL/min and noted that he is currently using data from claims, electronic health records, and registries to explore this issue because no randomized controlled trials are expected.

When considering DOACs for patients with liver disease, the Childs-Pugh score can be helpful. DOACs are fine for patients in Class A and no good for those in Class C, he said. For patients in the B category, an individual analysis of risks and benefits is required.

DOACs should also be avoided in patients who are taking strong p-glycoprotein or CYP 3A4 inhibitors or inducers, are on dual antiplatelet therapy, are pregnant, or have cancer. That last contraindication may be changing, however, with oncologists becoming more inclined to use this drug class, Dr. Deitelzweig said.

Another change in the anticoagulation field is duration of therapy after a VTE. The recommendation for initial therapy of provoked and unprovoked clots is the same: “Everybody for every VTE or PE gets, at minimum, three months and potentially longer based on bleeding risk,” he said.

After three months, though, patients with unprovoked clots are looking at a very different course of care under the latest guidelines. “It used to be at least three months. Now we're looking at extended therapy with no scheduled stop date. That's been a dramatic adjustment,” said Dr. Deitelzweig.

Of course, the benefits of extended therapy have to be balanced against the risks of bleeding. There are a number of scores for predicting clotting risk, including the Vienna Prediction Model and the DASH score. “I don't like people getting too bogged down among the scores, just to know what goes into these type of scores,” he said.

The latest American College of Chest Physicians guideline update offers a relatively simple system for scoring the risk of bleeding, which Dr. Deitelzweig described. It includes a list of risk factors, such as age, cancer, alcohol abuse, or anemia. Patients with none of the factors are low risk, those with one are moderate risk, and those with two or more are high risk. A chart in the guidelines provides estimates of the risk of bleeding in a year on anticoagulation—from 0.8% in low-risk patients to more than 6.5% in high-risk patients.

These predictions can then be used in discussion and decision making about duration of anticoagulation, he said.

No matter how long patients are going to be anticoagulated, continuity of their care is crucial. “We could have the most coordinated, comprehensive care known to humankind as hospitalists, and if we don't hand off well to the next in line downstream, that could lead to really bad things,” said Dr. Deitelzweig.

Patients need primary care follow-up soon after discharge, and it can be particularly helpful to schedule a visit for the same time as a dose change. For example, a patient may be on 10 mg of apixaban twice a day for a week, going down to 5 mg the next week. “That week is a natural time to have follow-up in the outpatient arena,” said Dr. Deitelzweig.

Making sure this goes smoothly takes group effort. “It's not just me as a hospitalist. We have our transition navigators who hand off from the inpatient to the outpatient case managers,” he said. “This is team-based management.”