NEW ORLEANS — Low-risk patients with acute pulmonary embolism (PE) can be discharged early after limited or no parenteral therapy and safely treated at home with oral rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals), the Home Treatment of Pulmonary Embolism (HoT-PE) trial suggests.
The primary efficacy outcome of recurrent symptomatic venous thromboembolism (VTE) or fatal PE within 3 months occurred in 3 of 525 patients (0.6%) in the intent-to-treat population. All 3 events were recurrent PE.
The efficacy rate was one third of the 1.7% threshold set by the investigators based on 3-month symptomatic VTE recurrence rates in prior home treatment studies and the EINSTEIN PE trial (one-sided upper 99.6% CI, 2.1%; P < .0001).
A prespecified interim analysis of the 525 ITT patients rejected the null hypothesis of fewer than 6 events occurring at an α level of 0.004, and the trial was prematurely stopped.
Further, just 2.3% of patients were rehospitalized due to suspected recurrent PE or bleeding, Stavros Konstantinides, MD, Democritus University of Thrace, Greece, reported here at the American College of Cardiology 68th Annual Scientific Session 2019 (ACC.19).
"The results of Hot-PE support the selection of appropriate PE patients for ambulatory treatment with a direct oral anticoagulant [DOAC], helping to reduce hospital-related complications and rationalize the use of health care resources," he said.
Commenting tor theheart.org | Medscape Cardiology session co-chair and past ACC president Mary Norine Walsh, MD, St. Vincent Heart Center of Indiana in Indianapolis, said, "I think it's good data to move us toward home treatment."
Patients in the United States are typically given heparin acutely with a DOAC added on, depending on acuity, but still remain in the hospital for about 5 days, she noted. The median hospital stay in the study was 34 hours, with 93.6% of patients discharged within 48 hours.
"Obviously I think this will get our guideline writers thinking about a shorter [stay]," but "this study was done in Europe and I would think a head-to-head comparison of some period of time with heparin versus initial DOAC would be needed."
As previously reported, the EINSTEIN PE trial showed that rivaroxaban halves major bleeding rates compared with standard therapy (enoxaparin and a vitamin K antagonist) in patients with acute symptomatic PE with or without DVT. Most patients, however, were initially started on a heparin drip or enoxaparin, observed Jay Giri, MD, associate director of the Cardiovascular Outcomes, Quality, and Evaluative Research, University of Pennsylvania, Philadelphia, who was not involved in the study.
Although a day or two of heparin may not seem like a big deal, he said, "It's not uncommon for only 30% to 50% of patients to be therapeutically anticoagulated at a 24-hour time point when you look at interim quality improvement data."
In HoT-PE, a single dose of heparin was given in only 10% of patients, Konstantinides reported.
"The main piece that this added is that you don't need to give a parenteral anticoagulant up front, you can just give the rivaroxaban," Giri told theheart.org | Medscape Cardiology. "That's an important, incremental piece of information that I feel adds to our understanding and builds on what was seen in Einstein PE."
The single-arm, phase 4 HoT-PE trial enrolled patients with objectively confirmed PE within 24 hours of presentation who were hemodynamically stable, were free of significant comorbidity requiring hospitalization, and had family or social background that would support home care. It also required the absence of right ventricular (RV) dysfunction and free-floating thrombi in the heart on the CT pulmonary angiography (CTPA) used to identify the PE or on echocardiography if a ventilation-perfusion scan was obtained, as was the case in about 15% of patients, Konstantinides said.
The first dose of rivaroxaban 15 mg twice daily was given in the hospital and continued for 3 weeks after discharge, followed by rivaroxaban once daily 20 mg, or 15 mg in select patients, for at least 3 months.
Patients were determined to be low risk using the Hestia criteria, which have a lot of overlap with the Pulmonary Embolism Severity Index (PESI) score but do not exclude patients who are older than age 80 years or have cancer, said Konstantinides. Notably, a meta-analysis reported just days ago found that RV dysfunction on echocardiography or CTPA increased the odds of early all-cause mortality fourfold in patients classified as low risk by the simplified PESI or Hestia criteria.
The mean age of the cohort was 56.7 years (range, 18 to 90 years), 45.7% were women, 98.5% were white, and 6.2% had active cancer.
The primary efficacy outcome rate was equally low in the per protocol (2 of 497 patients; 0.4%; P < .001) and worse-case-scenario (5 of 525 patients; 0.95%; P < .0015) sensitivity analyses.
Independently adjudicated safety outcomes were low, including major bleeding (6 of 519 patients), any clinically relevant bleeding (31 of 519), and at least one serious adverse event (58 of 519). Two deaths occurred in the trial, both due to advanced cancer.
Panelist Blyken Bozkurt, MD, Baylor College of Medicine, Houston, Texas, said, ""What's going to be important to recognize is that their scoring is a little bit more liberal than the PESI scoreWhat's going to be important to recognize than the PESI score, which is encouraging for real-life patients but still they excluded quite a significant proportion of patients who may have a confounder."
Of 2854 patients with confirmed acute PE, 2329 were excluded for life expectancy less than 3 months, at least one of the Hestia criteria, contraindications to rivaroxaban, RV dilation/dysfunction or thrombi, failure to consent, or "other reasons."
"I have no concerns in these patients that if a patient who fulfils all these criteria is included that this may not be safe enough," Konstantinides told theheart.org | Medscape Cardiology. "My concern is that this might be interpreted as too restrictive in sending a patient home."
Although the study could not address this, the results raise the issue of whether DOAC treatment could be delivered in the emergency department (ED) without hospital admission in low-risk patients with PE, observed Walsh and Giri.
"A lot of patients would probably love to go home with a just pill and know they are going to get better and not be at high risk of anything over 6 months without spending a couple of days in the hospital and have the bills associated with that," Giri said. "There's a lot of interest in setting up these protocols for EDs to pick who's safe to discharge from the ED, and this does make that a little easier because you don't have to give them heparin or Lovenox but can literally just give them a pill of rivaroxaban after you confirm these things and walk them out of the ED if they otherwise look good."
Konstantinides reports lecture and consultancy honoraria from Bayer AG, Boehringer Ingelheim, MSD, Pfizer/Bristol-Myers Squibb, Daiichi-Sankyo, Actelion, Biocompatibles Group UK, and Servier; and institutional research support from Bayer AG, Boehringer Ingelheim, Daiichi-Sankyo, MSD, and Actelion. Walsh reports no relevant financial disclosures. Giri reports serving on advisory board for AstraZeneca; serving on the board of directors for the PERT consortium; and receiving institutional grant support from Abbott and ReCor. Bozkurt reports consultant fees/honoraria from Bayer Healthcare Pharmaceuticals and Lantheus Medical Imaging Inc and serving on a data and safety monitoring board for LivaNova USA.
American College of Cardiology 68th Annual Scientific Session 2019 (ACC.19): Abstract 402-16. Presented March 16, 2019.
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Cite this: HoT-PE Puts Early Discharge, Home Treatment for Low-Risk PE on Front Burner - Medscape - Mar 16, 2019.