NEW ORLEANS — Certain patients with acute low-risk pulmonary embolism fared well with early discharge and home treatment with rivaroxaban, according to new data from the HoT-PE study.
“In the United States alone, around 100,000 deaths are annually attributable to PE. Although the case fatality rate appears to be decreasing over time, incident rates and overall mortality rates attributable to PE continue to increase with our aging population, showing that PE will be an increasingly greater problem for societies and health care systems in the years to come,” Stavros V. Konstantinides, MD, PhD, FESC, from the Center for Thrombosis und Hemostasis, University of Mainz, Germany, and Democritus University of Thrace, Greece, said at the American College of Cardiology Scientific Session.
Previous studies of early discharge and home treatment have been promising, he noted, but they were primarily small and the only major randomized trial was conducted 10 years ago in the era of vitamin K antagonists, according to Konstantinides. Direct oral anticoagulants, however, have simplified the initial phase of anticoagulation and transition from parenteral to oral treatments.
“The main objective of the HoT-PE trial was to determine whether early discharge and out-of-hospital treatment with rivaroxaban with patients with acute low-risk PE — with an emphasis on selected patients — would be effective, safe and, indirectly, feasible,” Konstantinides said.
Konstantinines and colleagues conducted the prospective, multicenter, international, single-arm trial with a planned enrollment of 1,050 patients with confirmed acute PE at 49 centers in seven countries throughout Europe. Because HoT-PE was a single-arm study, the researchers made assumptions about the possible outcome based on previous data, Konstantinides said. They hypothesized that the rate of the primary outcome of venous thromboembolism recurrence — symptomatic or fatal PE or deep vein thrombosis — would be less than 3% and the null hypothesis would be 3% or more. Their point estimate was 1.7% in this low-risk population, which was based on a meta-analysis of home treatment trials dating back to the vitamin K antagonist era.
Certain patients with acute low-risk pulmonary embolism fared well with early discharge and home treatment with rivaroxaban, according to new data from the HoT-PE study.
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After a planned interim analysis after the first 525 patients — with the objective of early termination of the trial if the null hypothesis could be rejected with 99.6% certainty — the trial stopped enrollment.
The mean age was 57 years, 46% were women and 98% were white. Most patients had good renal function, with only 5% having a creatinine clearance below 50 mL/min. Konstantinides noted that 6% of the patients had cancer and 20% had a simplified PESI score of 1 or more, suggesting that this study was more inclusive of patients for home treatment than if inclusion criteria were based on PESI or simplified PES score alone.
They used the Hestia criteria to determine if patients with PE were low-risk. The researchers also included patients who were hemodynamically stable, had no serious comorbidity that would mandate hospitalization for PE and met criteria indicating that they had the necessary social and family support to be sent home early.
Importantly, patients with right ventricular dysfunction were excluded, as data have shown that even those who are considered to be low-risk according to clinical scores have a four-fold increased risk for 30-day mortality in the presence of RV dysfunction, Konstantinides said.
Of the patients enrolled, 94% were discharged from the hospital within 48 hours, as stipulated by the protocol, and 96% spent 2 nights or less in the hospital, as tolerated by the protocol, according to Konstantinides. Nearly all patients received at least one dose of rivaroxaban (Xarelto, Janssen/Bayer) and 94% of patients completed at least 3 months of treatment.
Patients were followed for 1 year for survival.
The primary efficacy outcome — recurrence of symptomatic venous thromboembolism or fatal PE — occurred in 0.6% of the intention-to-treat population, which yielded a one-sided 99.6% upper confidence limit of 2.1%, Konstantinides said. All three events were due to recurrent PE, with no isolated DVT as an outcome and no deaths related to VTE in general.
The researchers also conducted two sensitivity analyses. In the per-protocol population, which included patients who had received at least one dose of rivaroxaban and had been discharged within 48 hours, the rate of the primary outcome was 0.4%, with a one-sided 99.6% upper confidence limit of 1.6%.
In a “worst-case scenario” analysis in which two more patients for whom incomplete data were available during follow-up were imputed as having the primary outcome, the rate was 0.95%, with a one-sided 99.6% upper confidence limit of 1.99%.
Major bleeding occurred in 1.2% of patients, including three cases of uterine bleeding, two cases of gastrointestinal bleeding and one intracranial bleed. Any clinically relevant bleeding occurred in 6% of patients and 11.2% experienced a serious adverse event.
During the 3-month follow-up, only 2.3% of the patients were rehospitalized due to suspected recurrent PE or bleeding. In the final diagnosis of these patients, there was confirmation of recurrent PE or major bleeding in 7 of 12 cases, one case of clinically relevant non-major bleeding and two cases of death — both of which were due to cancer.
“In these patients with acute low-risk PE, including absence of RV dysfunction and intracardiac thrombi, early discharge and home treatment with rivaroxaban was effective, safe and also feasible, as judged by the high rate of adherence to the protocol,” Konstantinides said. “The results of HoT-PE also support the selection of appropriate patients for ambulatory treatment with a direct oral anticoagulant, helping to reduce heart-related complications and rationalize the use of health care resources.” – by Melissa Foster
Konstantinides S. Featured Clinical Research I. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosures: Konstantinides reports he has received lecture and consultant honoraria from Actelion, Bayer AG, Biocompatibles Group UK, Boehringer Ingelheim, Daiichi Sankyo, Merck Sharpe and Dohme, Pfizer/Bristol-Myers Squibb and Servier and he has received institutional research support from Actelion, Bayer AG, Boehringer Ingelhim, Daiichi Sankyo and Merck Sharpe and Dohme.
Editor’s Note: This article was updated on March 19, 2019 to correct bleeding data. The Editors regret the error.