New real-world study of patients with venous thromboembolism (VTE) and morbid obesity shows safety and effectiveness of Xarelto were similar to warfarin, with significantly less healthcare resource utilization (HRU) and total medical costs
TITUSVILLE, N.J., September 20, 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced new real-world evidence confirming XARELTO® (rivaroxaban) reduced the risk of recurrent venous thromboembolism (VTE) – or blood clots – in patients who are morbidly obese, with effectiveness and safety similar to warfarin. Notably, patients taking XARELTO® had significantly reduced healthcare resource utilization (HRU) and total medical costs compared to those taking warfarin. Results of this study were recently published in Thrombosis Research.
Approximately 40 percent of the U.S. population have obesity and about 8 percent have morbid obesity. Obesity increases the risk of VTE by two- to six-fold compared with non-obese patients.[i] Typically, morbidly obese patients are treated with older anticoagulants, such as warfarin, and require more laboratory monitoring than patients of normal weight. In addition, morbidly obese patients are often underrepresented in Phase 3 studies.
“This is the first large-scale, real-world study to evaluate a direct oral anticoagulant (DOAC) in morbidly obese patients with VTE, and the first to identify healthcare resource utilization and medical costs in this population,” said Alex C. Spyropoulos, M.D., Professor of Medicine, The Donald and Barbara Zucker School of Medicine, Hofstra University, Northwell Health at Lenox Hill Hospital, New York, N.Y. “We now know from this research that rivaroxaban is as effective and safe as dose-adjusted warfarin when treating morbidly obese patients, without the need for routine anti-Xa measurements, and with significantly lower healthcare resource utilization. Physicians should feel confident in prescribing rivaroxaban for managing VTE in this population.”
In 2016, the International Society on Thrombosis and Haemostasis (ISTH) published a guidance statement recommending against DOAC use in morbidly obese patients. This recommendation was based on limited clinical data and concerns about available pharmacokinetic/pharmacodynamic (PK/PD) evidence from another DOAC that suggested a decrease in drug levels with increased body weight.[ii]Published data for XARELTO®, however, found that the medicine’s PK/PD were not meaningfully influenced by body weight, and this research is reflected in the XARELTO® prescribing information.
“Obesity affects millions of Americans and is a significant risk factor for VTE and NVAF,” said Paul Burton, M.D., Ph.D., FACC, Vice President, Medical Affairs, Internal Medicine, Janssen Scientific Affairs, LLC. “These real-world studies, coupled with the consistent PK/PD and clinical data for XARELTO® in obese patients with VTE or NVAF, underpin the broad clinical utility of XARELTO® and provide clinicians with the evidence to consider an alternative option to warfarin.”
More than 5,000 morbidly obese patients (those who had a body mass index [BMI] of ≥40) were included in the study, with half receiving XARELTO® and half receiving warfarin. There were 2,890 matched pairs in the intent-to-treat (ITT) analysis and 2,832 pairs in the on-treatment analysis.The following observations for the ITT analysis were made:
· Recurrent VTE: The risk of recurrent VTE was not significantly different between XARELTO®and warfarin (16.8 percent vs. 15.9 percent; Odds Ratio [OR]: 0.99; 95 percent confidence interval [CI]: 0.85 to 1.14; p=0.8443).
· Major Bleeding: The study found significantly fewer major bleeding events for those taking XARELTO® compared to those taking warfarin (1.8 percent vs. 2.5 percent; OR: 0.66; 95 percent CI: 0.45 to 0.98; p=0.0388).
· HRU: XARELTO® was associated with significantly lower HRU compared to treatment with warfarin. Specifically, hospitalizations occurred in 35.1 percent and 38.6 percent, respectively (OR: 0.86; 95 percent CI: 0.77 to 0.96; p=0.0057). XARELTO® patients, on average, had 19 fewer per patient per year (PPPY) outpatient visits, including laboratory encounters, compared to warfarin-treated patients (93 vs. 112 encounters; p<0.0001).
· Medical Costs: XARELTO® treatment yielded significantly less HRU and total medical costs (hospitalizations, emergency room, outpatient and office visits, skilled nursing facility/long-term care), with similar total healthcare costs (including total medical costs and pharmacy costs) between groups. Average total medical costs PPPY were $2,829 lower with XARELTO® compared to warfarin ($34,824 vs. $37,653; p=0.0201), which were mainly driven by hospitalization costs.
The on-treatment analysis found no significant differences for recurrent VTE and major bleeding between XARELTO® and warfarin, with significantly lower HRU and total medical costs associated with XARELTO®.
The results of this VTE study are consistent with data across body weights[iii] from the EINSTEIN DVT and EINSTEIN PE randomized clinical trials, which were the Phase 3 registration trials for XARELTO® in VTE (deep vein thrombosis or DVT, and pulmonary embolism or PE). Additionally, this real-world VTE study complements the only other large-scale, real-world study[iv] of over 7,000 patients with NVAF and morbid obesity where consistent effectiveness, safety and reduction in healthcare and total medical costs with XARELTO® were shown. The safety and effectiveness align with what was observed in ROCKET AF, the Phase 3 registration trial for XARELTO® in NVAF.
This retrospective study analyzed data from two U.S. claims databases (Truven MarketScan Commercial Claims and Encounters database and MarketScan Medicare Supplemental database).Adult patients who had one or more medical claims with a VTE diagnosis between December 1, 2012 and September 30, 2016 were eligible for the study. Of these patients, those who initiated treatment with XARELTO® or warfarin within 28 days of VTE diagnosis and had at least one diagnosis of morbid obesitywere included. Researchers utilized propensity score matching to create 2,890 matched pairs of patients who initiated treatment with either XARELTO® or warfarin. Most patients in the XARELTO® cohort initiated treatment with the 15 mg twice-daily dose.
The study included two analyses: ITT and on-treatment. The primary outcome was the risk of recurrent VTE, defined as a hospitalization or ER visit with a primary diagnosis of VTE during the follow-up period. Secondary outcomes included major bleeding risk, HRU and costs.
Participants were ineligible if they had a diagnosis of VTE or atrial fibrillation at any time prior to the treatment initiation, or if they had an oral anticoagulant prescription prior to treatment initiation.
All real-world studies have limitations. This study was a retrospective claims analysis with inherent limitations. In this study, the use of administrative claims data may have been coded incorrectly or inconsistently. Residual confounding due to unmeasured confounders not included in the propensity match could not be fully excluded. A claim for a prescription does not necessarily indicate that the medication was taken. The use of diagnosis codes to identify patients who have morbid obesity may have been underestimated as height and weight were not available to confirm body mass index status.
Please click here for full Prescribing Information, including Boxed Warnings, and Medication Guide.
Trademarks are those of their respective owners. Janssen and Bayer together are developing rivaroxaban. For more information about XARELTO®, visit www.xarelto.com.
About Janssen Cardiovascular & Metabolism
In Cardiovascular & Metabolism (CVM), we take on the most pervasive diseases that burden hundreds of millions of people and healthcare systems around the world. As part of this long-standing commitment and propelled by our successes in treating type 2 diabetes (T2D) and thrombosis, we advance highly differentiated therapies that prevent and treat life-threatening cardiovascular, metabolic and retinal diseases. Uncovering new therapies that can improve the quality of life for this large segment of the population is an important endeavor – one which Janssen CVM will continue to lead in the years to come. Our mission is global, and local and personal. Together, we can reshape the future of cardiovascular, metabolic and retinal disease prevention and treatment. Please visit
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at . Follow us at www.twitter.com/JanssenUS. Janssen Pharmaceuticals, Inc. and Janssen Scientific Affairs, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Dr. Alex Spyropoulos worked directly with Janssen Scientific Affairs, LLC and was compensated for his work on this study.
 For the ITT analysis, patients were followed until the first event of interest or until the end of the 12-month observation period.
 For the on-treatment analysis, patients were followed from treatment initiation to discontinuation.
[i] A.L. Freeman, R.C. Pendleton, M.T. Rondina. Prevention of venous thromboembolism in obesity. Expert Rev Cardiovasc Ther. 2010;8:1711-1721.
[ii] V. Upreti, et al. Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br J Clin Pharmacol. 2013 Dec;76(6):908-16. doi: 10.1111/bcp.12114.
[iii] M. Di Nisio, M.C. Vedovati, A. Riera-Mestre, et al. Treatment of venous thromboembolism with rivaroxaban in relation to body weight. A sub-analysis of the EINSTEIN DVT/PE studies. Thromb Haemost. 2016;116:739-746.
[iv] E.D. Peterson, et al. Comparative effectiveness, safety, and costs of rivaroxaban and warfarin among morbidly obese patients with atrial fibrillation. Am Heart J. 2019 Jun;212:113-119.