May 25, 2018: Bayer and its research and development partner, Janssen Research & Development, LLC, announced the results of a new real-world study. Insurance claims data from the US Truven MarketScan database indicated that compared with warfarin treatment, treatment with Xarelto®In frail patients with non-valvular atrial fibrillation treated with rivaroxaban, the risk of stroke and systemic thromboembolism was reduced by 32% over two years, including a 31% reduction in the risk of ischemic stroke. This study also evaluated the efficacy and safety of apixaban and dabigatran; neither drug significantly reduced the risk of stroke and systemic embolism compared with warfarin during the two-year follow-up period. The findings have been published in the Journal of the American Heart Association.[i]。
Frailty is a common clinical condition, particularly prevalent among elderly patients, who face greater difficulty in recovering from cardiovascular events and have a poorer prognosis. [ii],[iii]. The risk of frailty in patients with non-valvular atrial fibrillation is four times that of patients without non-valvular atrial fibrillation.[ii]. Non-valvular atrial fibrillation is a type of atrial fibrillation, with approximately 33.5 million patients worldwide.[iv]Atrial fibrillation increases the risk of stroke fivefold, and 15%–20% of strokes are caused by atrial fibrillation.[v],[vi]. Nevertheless, studies have shown that frail patients with non-valvular atrial fibrillation are more likely to be under-anticoagulated.[vii],[viii],[ix]。
“In clinical practice, there is no widely accepted effective approach to managing frail patients; consequently, some patients receive no treatment at all and remain at high risk of stroke,” said Dr. Craig Coleman of the University of Connecticut. “The results presented here demonstrate that long-term use of rivaroxaban reduces the risk of stroke and systemic embolism in frail patients without increasing the risk of major bleeding, providing important insights for clinicians on selecting well-tolerated and effective therapies for this patient population.”
Frail patients with non-valvular atrial fibrillation treated with rivaroxaban, apixaban, or dabigatran were identified from the US Truven MarketScan insurance claims database and matched 1:1 with warfarin users. Follow-up continued for two years or until the occurrence of an event, loss of insurance coverage, or end of follow-up. The primary effectiveness endpoint was stroke (ischemic or hemorrhagic) or systemic embolism, and the primary safety endpoint was major bleeding.
“The efficacy and safety of rivaroxaban have been confirmed in many types of patients with non-valvular atrial fibrillation. The results of this study support its effectiveness in frail patients in the real-world setting, a population that often presents greater challenges for achieving adequate anticoagulation,” said Martin van Eickels, Medical Director at Bayer. “Complementing clinical trial data, such real-world evidence provides rich and multifaceted insights for the continuously evolving management of cardiovascular diseases.”
Two-year follow-up observations revealed that, compared with warfarin, rivaroxaban significantly reduced the risk of stroke or systemic embolism by 32% (HR = 0.68; 95% CI = 0.49–0.95), including a 31% reduction in the risk of ischemic stroke (HR = 0.69; 95% CI = 0.48–0.99). Additionally, the incidence of major bleeding was similar in the rivaroxaban and warfarin groups (HR = 1.07; 95% CI = 0.81–1.32).
In this study, compared with warfarin, neither apixaban nor dabigatran reduced the risk of stroke or systemic thromboembolism (HR = 0.78; 95% CI = 0.46–1.35 for apixaban; HR = 0.94; 95% CI = 0.60–1.45 for dabigatran). The rates of major bleeding with apixaban (HR = 0.72; 95% CI = 0.49–1.06) and dabigatran (HR = 0.87; 95% CI = 0.63–1.19) were similar to those in the warfarin group.
About the Study
Based on insurance claims data from the US MarketScan database between November 2011 and December 2016, researchers identified 19,077 patients who had not previously received anticoagulant therapy and were initiating treatment with rivaroxaban, apixaban, dabigatran, or warfarin. These patients had at least 12 consecutive months of insurance coverage and were diagnosed as frail. Frailty was assessed using the Johns Hopkins Claims-based Frailty Indicator. This scoring algorithm comprises 21 indicators, including demographics, comorbidities, and physical and cognitive function.
This retrospective study included a total of 10,754 patients: 2,635 treated with rivaroxaban, 1,392 with apixaban, 1,350 with dabigatran, and 5,377 with warfarin. Patients in the rivaroxaban, apixaban, and dabigatran groups were matched 1:1 with warfarin users according to predefined criteria to minimize baseline differences among the groups.
In addition to the two-year data, one-year patient outcomes were also tracked. The researchers found that in the first year, there were no significant differences between rivaroxaban, apixaban, or dabigatran and warfarin in reducing stroke and systemic embolism. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding. The proportions of major bleeding in the rivaroxaban and dabigatran groups were similar to those in the warfarin group, but both significantly reduced the incidence of intracranial hemorrhage.
Real-world data can serve as a supplement to data obtained from randomized trials, providing additional information on a drug’s performance in routine clinical practice. However, it has limitations and cannot serve as standalone evidence to determine the efficacy and/or safety of a treatment.
References:
[i] Martinez BK, Sood NA, Bunz TJ, Coleman, CI. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in frail patients with nonvalvular atrial fibrillation. J Am Heart Assoc. 2018;7(2).
[ii] Polidoro A, Stefanelli F, Ciacciarelli M, Pacelli A, Di Sanzo D, Alessandri C. Frailty in patients affected by atrial fibrillation. Archives of gerontology and geriatrics. 2013;57(3):325-7.
[iii] Villacampa-Fernández P, Navarro-Pardo E, Tarín JJ, Cano A. Frailty and multimorbidity: two related yet different concepts. Maturitas. 2017;95:31-5.
[iv] Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty JH, Zheng ZJ, Forouzanfar MH. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2013:CIRCULATIONAHA-113.
[v] American Heart Association. Prevention Strategies for Atrial Fibrillation. Retrieved from: http://www.heart.org/HEARTORG/Conditions/Arrhythmia/AboutArrhythmia/Prevention-Strategies-for-Atrial-Fibrillation-AFib-or-AF_UCM_423784_Article.jsp#.VvRBcuIrKUk
[vi] Atrial Fibrillation Society. The AF Report Atrial Fibrillation: Preventing a Stroke Crisis. Available at http://www.preventaf-strokecrisis.org/files/files/The%20AF%20Report%2014%20April%202012.pdf. Accessed May 2018.
[vii] Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing 2009;38:156–162.
[viii] 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.
[ix] 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.