By Marilynn Larkin
NEW YORK (Reuters Health) - 5/6/2019
Carefully selected patients with acute low-risk pulmonary embolism (PE) may be discharged early and treated at home safely and effectively with rivaroxaban, researchers say.
Dr. Stavros Konstantinides of Johannes Gutenberg University in Mainz and colleagues in seven countries conducted a prospective multicenter, single-arm trial in patients with acute low-risk PE - i.e., no hemodynamic instability, no right ventricular dysfunction or intracardiac thrombi, and no serious comorbidities. Up to two nights of hospital stay were permitted.
Rivaroxaban was given after study enrollment for three months or longer. Initially, 15 mg was given twice daily over a mean period of 21 days. Then the standard maintenance dosage of 20 mg was given once daily over a mean period of 68 days; the reduced dosage of 15 mg once daily was given to four patients.
The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within three months of enrollment.
An interim analysis was planned after the first 525 patients were assessed, with prespecified early termination of the study if there were <6 primary outcome events (i.e., if the null hypothesis could be rejected at the level of alpha = 0.004).
As reported online May 23 in the European Heart Journal, of the 525 patients included in the interim analysis (mean age, 57; 46% women), three had a symptomatic non-fatal VTE recurrence - a number sufficiently low to fulfill the condition for early trial termination.
Major bleeding occurred in six (1.2%) of the 519 patients in the safety population. There were two cancer-related deaths (0.4%).
Dr. Nick Kim, section chief for pulmonary vascular medicine at UC San Diego Health, told Reuters Health by email, "The (current) study was welcome news for patients diagnosed with low-risk pulmonary embolism. Instead of spending days in a hospital, patients in the study received home oral anticoagulant therapy with rivaroxaban with demonstrated safety and efficacy."
"These results, however, should not be extrapolated to all cases of pulmonary embolism since only mild, low-risk cases meeting very specific clinical criteria were studied," he added.
Dr. Jose Wiley, director of the Cardiac Catheterization Laboratory (Moses Division) and of Endovascular Interventions at Montefiore Einstein Center for Heart and Vascular Care in New York City, commented, "The results of this study validate the commonly known concept of 'facilitated early discharge' for patients with low-risk PE, which was used in two previous trials of vitamin K antagonists in PE."
"This study adds to current knowledge by demonstrating that rivaroxaban, a non-vitamin K antagonist oral anticoagulant, can be used safely with this strategy, but only in truly low-risk PE patients," he told Reuters Health by email. "Low-risk patients, defined by clinical criteria, account for approximately 33% of the PE population. However, if RV dysfunction and intracardiac thrombi are added as exclusions to the clinical criteria, the PE population considered at 'true low risk' may be as low as 20%."
"This study has several limitations," he added. "First, there is no control arm with standard parenteral heparin followed by VKA. Second, 98.5% of the study population was Caucasian. Third, a significant population at risk for PE are octogenarians, and patients over age 80 represented less than 5% of the study population."
"Rivaroxaban should be considered in our treatment armamentarium when the above considerations are addressed in a randomized, controlled study," Dr. Wiley concluded.
Dr. Konstantinides did not respond to requests for a comment.
The study drug was provided by Bayer. A number of coauthors receive fees from the company.
Eur Heart J 2019.