The Janssen Pharmaceutical Companies of Johnson & Johnson on Thursday announced new real-world data that showed frail patients with non-valvular atrial fibrillation (NVAF) experienced significantly fewer strokes and systemic emboli when treated with Xarelto (rivaroxaban) over a two-year period compared to those taking warfarin.
Specifically, long-term Xarelto use reduced the risk of stroke and systemic embolism by 32 percent and ischemic stroke alone by 31 percent compared to warfarin, with no significant increase in major bleeding. Results from the study, which also assessed the efficacy and safety of apixaban and dabigatran each versus warfarin, were recently published in the Journal of the American Heart Association.
Affecting nearly six million Americans, NVAF increases a person’s risk of stroke by five times and accounts for 15 to 20 percent of all strokes.1,2 Frailty is a common clinical syndrome mainly seen in older adults that makes it harder for them to recover from stressful cardiovascular events and vulnerable for poorer health outcomes.
People with NVAF are four times more likely to be classified as frail than people without NVAF,3 and research has shown frail people with NVAF are less likely to receive anticoagulation than non-frail people.4, 5, 6
“There is not widespread consensus on the best way to manage frail patients with NVAF in clinical practice, which is why some patients are not treated at all and remain at high risk of having a stroke,” said Craig Coleman, PharmD, professor of pharmacy practice, University of Connecticut. “These results show long-term rivaroxaban use reduced stroke and systemic embolism in a vulnerable patient group, without increasing the risk of major bleeding. They also give physicians important insights into a well-tolerated, effective approach to treat their frail patients with NVAF.”
In the study, researchers used U.S. Truven MarketScan claims data and identified frail patients with NVAF taking Xarelto, apixaban, or dabigatran. Each treatment group was matched separately with warfarin users in a 1:1 ratio and followed for up to two years or until an event, insurance disenrollment or end of follow-up occurred. The primary efficacy outcome was stroke (ischemic or hemorrhagic) or systemic embolism. Major bleeding was the primary safety outcome.
Researchers made the following two-year observations:
· Xarelto was associated with a 32 percent reduction in stroke or systemic embolism (HR=0.68; 95% CI=0.49-0.95) and 31 percent reduction in ischemic stroke alone (HR=0.69; 95% CI=0.48-0.99) compared to warfarin.
· Xarelto had similar rates of major bleeding compared to warfarin (HR=1.07; 95% CI=0.81-1.32).
· Though both apixaban and dabigatran treatment were associated with numerically fewer strokes, neither statistically significantly reduced the risk of stroke or systemic embolism at two years compared to warfarin (HR=0.78; 95% CI=0.46-1.35 and HR=0.94; 95% CI=0.60-1.45).
· Rates of major bleeding also were evaluated for apixaban versus warfarin (HR=0.72; 95% CI=0.49-1.06) and dabigatran versus warfarin (HR=0.87; 95% CI=0.63-1.19).
“This study adds to the growing body of evidence supporting the positive efficacy and safety profile of Xarelto across a broad spectrum of patients with NVAF, which now includes the frail population,” said Paul Burton, M.D., Ph.D., FACC, vice president, medical affairs, Janssen Pharmaceuticals, Inc. “Real-world data like this study are critical to informing and helping physicians best treat their patients’ cardiovascular diseases.”
About the Frailty Study
A total of 19,077 patients were identified using claims data from U.S. MarketScan databases from November 2011 to December 2016. These patients were new users of anticoagulant therapy with Xarelto, apixaban, dabigatran, or warfarin, who had not been previously treated with an anticoagulant.
They also had at least 12 months of continuous insurance coverage, and were considered frail. Frailty was determined using the Johns Hopkins Claims-based Frailty Indicator scoring algorithm, which weighs 21 criteria identifiable in claims data, including demographics, comorbidities, and physical and cognitive dysfunction.
Each eligible Xarelto, apixaban, and dabigatran user was propensity score matched to a warfarin user in a 1:1 ratio, which helped minimize the presence of baseline differences between cohorts. A total of 10,754 patients were included in the retrospective study, with 2,635 taking Xarelto, 1,392 apixaban, 1,350 dabigatran, and 5,377 warfarin. This study was supported by Bayer AG, Berlin, Germany.
Real-world data have the potential to supplement randomized controlled trial data by providing additional information about how a medicine performs in routine medical practice; however, they have limitations and cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment.
Additionally, it is possible some of the analyses within this specific study may not have been sufficiently powered based on smaller sample sizes, according to Janssen.
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References:
1 Colilla S et al. Estimates of Current and Future Incidence and Prevalence of Atrial Fibrillation in the U.S. Adult Population. Am J Cardiol 2013;112(8):1142-1147.
2 American Heart Association (2014, April 16). Prevention Strategies for Atrial Fibrillation. Retrieved from: https://www.heart.org/HEARTORG/Conditions/Arrhythmia/AboutArrhythmia/Prevention-Strategies-for-Atrial-Fibrillation-AFib-or-AF_UCM_423784_Article.jsp#.VvRBcuIrKUk
3 Coleman CI, Bunz TJ, Eriksson D, Meinecke AK and Sood NA. Effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes: an administrative claims database analysis. 2018 April; doi: 10.1111/dme.13648<https://onlinelibrary.wiley.com/doi/epdf/10.1111/dme.13648>.
4 Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilization of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing2009;38:156–162.
5 Induruwa I, Evans NR, Aziz A, Reddy S, Khadjooi K, Romero-Ortuno R. Clinical frailty is independently associated with non-prescription of anticoagulants in older patients with atrial fibrillation. Geriatr Gerontol Int 2017;17:2178–2183.
6 Lefebvre MC, St-Onge M, Glazer-Cavanagh M, Bell L, Kha Nguyen JN, Viet-Quoc Nguyen P, Tannenbaum C. The effect of bleeding risk and frailty status on anticoagulation patterns in octogenarians with atrial fibrillation: the FRAIL-AF study. Can J Cardiol 2016;32:169–176.
(Source: Janssen Pharmaceutical Companies of Johnson & Johnson)
Filed Under: Drug Discovery