eISSN: 2300-6722
ISSN: 1899-1874
Medical Studies/Studia Medyczne
Bieżący numer Archiwum Artykuły zaakceptowane O czasopiśmie Suplementy Rada naukowa Bazy indeksacyjne Prenumerata Kontakt Zasady publikacji prac
Panel Redakcyjny
Zgłaszanie i recenzowanie prac online
3/2013
vol. 29
 
Poleć ten artykuł:
Udostępnij:
Opis przypadku

New oral anticoagulants in the prevention of stroke

Konrad Jarząbek
,
Dawid Bąkowski
,
Beata Wożakowska-Kapłon

Studia Medyczne 2013; 29 (3): 264–266
Data publikacji online: 2013/10/25
Plik artykułu:
Pobierz cytowanie
 
Metryki PlumX:
 

Introduction

Atrial fibrillation, occurring in about 1–2% of the population, is the most common type of sustained heart arrhythmia [1, 2]. The number of patients afflicted with atrial fibrillation has doubled during the last 50 years and is still growing, owing to the expanding life expectancy and the decrease in the level of mortality caused by heart diseases especially among men after 75 years old. Atrial fibrillation confers a 5-fold risk of stroke and about 20% of strokes are attributed to atrial fibrillation [1–3]. Ischaemic strokes caused by atrial fibrillation are often fatal and the patients who survive suffer from a greater disability and have a higher risk of another stroke. Oral vitamin K antagonists are effective in the prevention of stroke but are more inconvenient in use. The necessity of individual dose adjustment and their interactions with a large number of substances often impair the quality of treatment

[4–7]. According to many clinical studies less than a half of the patients have the correct level of international normalized ratio (INR) [8].

We present a case of a patient with atrial fibrillation treated with rivaroxaban.

Case report

A 77-year-old woman with coronary heart disease, hypertension, heart failure, with rheumatoid arthritis, after ischaemic stroke and with recurrent episodes of haemorrhages was admitted to a cardiology department due to loss of consciousness. The laboratory tests revealed decreased haemoglobin level (11.4 g/dl), renal insufficiency (estimated glomerular filtration rate (eGFR) 34 ml/min) and a correct level of aminotransferases activity. Moderate heart failure features (ejection fraction (EF) – 45%) and atrial fibrillation with left bundle branch block in the electrocardiogram were present on admission to hospital. Holter ECG monitoring revealed periods of sinusoid rhythm interrupted by atrial fibrillation episodes connected with advanced atrioventricular block. This led to a decision of heart pacer implantation. Due to a high risk of thromboembolic complications the patient required oral anticoagulation. Because of the insufficient control of the INR level and the necessity to modify the dosage of the warfarin over four times during the last 6 months (INR lability), the further use of oral vitamin K antagonist was highly questionable. Considering the necessity of preventing stroke recurrence, and the possible haemorrhagic complications (5 points on the HAS – BLED scale) rivaroxaban was prescribed. Because of the level of GFR the dose was decreased to 15 mg once daily.

Discussion

Despite thoroughly documented benefits of the anticoagulation treatment, its application is observed to be limited. It has been indicated in American studies that only 40% of patients with a high risk of stroke caused by atrial fibrillation receive oral anticoagulation [9, 10]. Furthermore, according to another multicentre study, not only an insufficient number of patients with atrial fibrillation received oral anticoagulation, but also nearly 60% of them were below the therapeutic range of INR [8, 10, 11]. Maintaining an appropriate level of INR during less than 60% of the therapeutic time undermines the beneficial aspects of the treatment. There is a number of factors decreasing the efficiency of oral anticoagulation: unsatisfactory cooperation with the patient, lack of sufficient conviction for this method of treatment, and little knowledge of the scientific evidence including false opinions of overestimated danger of hemorrhagic complications of oral anticoagulation [12–14]. Hopefully, implementing new methods of treatment connected with a decreased risk of haemorrhagic complications will improve the situation. In many cases rivaroxaban can be an alternative to oral vitamin K antagonists.

It is a highly selective factor Xa inhibitor which disrupts the blood coagulation pathway preventing both the activation of prothrombin and formation of a thrombus [15–17]. The ROCKET AF study provided confirmation of its non-inferiority regarding the prevention of stroke in comparison to warfarin and a significant reduction of major bleeding, intracranial haemorrhage and fatal bleeding in the rivaroxaban group. The Rocket AF study conclusions and practical aspects of the treatment should convince both the doctor and the patient that rivaroxaban can provide more consistent and predictable anticoagulation than warfarin. In the case of the above-presented patient, problems with individual dosing, INR lability and practical problems with frequent INR monitoring led to the decision of substituting warfarin with rivaroxaban. Shifting from warfarin to rivaroxaban in patients with a stable INR level is highly questionable and should be considered very carefully. The Rocket AF study did not provide evidence for the superiority of rivaroxaban over warfarin in terms of preventing stroke and the number of bleeding incidents was comparable [18, 19]. Thus, implementing rivaroxaban in the case of our patient may not necessarily diminish the risk of nose bleeding episodes, which occurred most frequently during periods of labile INR level. On the other hand, taking into consideration the steroid therapy which our patient was subjected to and its possible interactions with the oral vitamin K antagonists as well as its adverse influence on the digestive system, the risk of major bleeding incidents could be decreased with rivaroxaban. According to clinical studies, dexamethasone used in the therapeutic oral doses can increase the level of warfarin, which would require frequent INR monitoring [20].

Implementing new oral anticoagulants in prevention of stroke for patients with atrial fibrillation appears to be a significant alternative, though it should not be regarded as a solution to all the therapeutic problems. The financial cost of the therapy still poses a serious dilemma, as well as the lack of a selective antidote and difficulties with monitoring the efficacy of the treatment.

Conclusions

Oral vitamin K antagonists used in the prevention of stroke require frequent INR monitoring, have a wide range of interactions with other substances including food ingredients and may inflict practical problems. Maintaining an inappropriate level of INR during most of the therapeutic time makes the oral vitamin K antagonists inefficient in preventing stroke. Rivaroxaban is non-inferior to warfarin in the prevention of stroke, but reduces the number of major bleeding incidents. Rivaroxaban should be considered for patients controlling the INR irregularly, or with a labile INR level.

References

 1. The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC): 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J 2012; 33: 2719–2747.

 2. Camm AJ, Kirchof P, Lip G, et al. Wytyczne dotyczące postępowania u chorych z migotaniem przedsionków. Kardiol Pol 2010; 68 supl. VII: 487–566.

 3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–988.

 4. Albers GW, Yim JM, Belew KM, et al. Status of antithrombotic therapy for patients with atrial fibrillation in university hospitals. Arch Intern Med 1996; 156: 2311–2316.

 5. Go AS, Hylek EM, Borowsky LH, et al. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Ann Intern Med 1999; 131: 927–934.

 6. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883–891.

 7. Kołcz M, Bała M, Jaeschke R. Czy u chorych z niezastawkowym migotaniem przedsionków rywaroksaban jest równie skuteczny jak warfaryna w zmniejszaniu ryzyka udaru mózgu i zatoru systemowego? Med Prakt 2012; 2: 71–77.

 8. Rose AJ, Hylek EM, Ozonoff A, et al. Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the Veterans Affairs Study to Improve Anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes 2011; 4: 22–29.

 9. Cohen N, Almoznino-Sarafian D, Alon I, et al. Warfarin stroke prevention still underused in atrial fibrillation: patterns of omission. Stroke 2000; 31: 1217–1222.

10. Porębska A, Nowacki P. Migotanie przedsionków jako istotny czynnik ryzyka udaru niedokrwiennego mózgu. Neurol Neurochir Pol 2005; 39: 134–140.

11. Scott PA, Pancioli AM, Davis LA, et al. Prevalence of atrial fibrillation and antithrombotic prophylaxis in emergency department patients. Stroke 2002; 33: 2664–2669.

12. Undas A. Trudne problemy terapeutyczne u chorych leczonych doustnymi antykoagulantami z grupy antagonistów antywitaminy K. J Transf Med 2011; 4: 185–192.

13. Deplanque D, Leys D, Parnetti L, et al. Stroke prevention and atrial fibrillation: reasons leading to an inappropriate management. Main results of the SAFE II study. Br J Clin Pharmacol 2004; 57: 798–806.

14. Pradhan AA, Levine MA. Warfarin use in atrial fibrillation: A random sample survey of family physician beliefs and preferences. Can J Clin Pharmacol 2002; 9: 199–202.

15. Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939: an oral, direct Factor Xa inhibitor – after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005; 61: 873–880.

16. Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 2008; 24: 2757–2765.

17. Eriksson BI, Borris LC, Dahl OE, et al. Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism. Annu Rev Med 2011; 62: 41–57.

18. ROCKET AF Study Investigators: Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study. Am Heart J 2010; 159: 340–347.

19. Paikin JS, Manolakos JJ, Eikelboom JW. Rivaroxaban for stroke prevention in atrial fibrillation: a critical review of the Rocket AF study. Expert Rev Cardiovasc Ther 2012; 10: 965–972.

20. Sellam J, Costedoat-Chalumeau N, Amoura Z. Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis. Joint Bone Spine 2007; 74: 446-452.



Address for correspondence:



Beata Wożakowska-Kapłon


Swietokrzyskie Centre of Cardiology

1st Clinic of Cardiology

District Hospital in Kielce

ul. Grunwaldzka 45, 25-736 Kielce, Poland

Phone: +48 41 367 13 91

Fax: +48 41 367 13 96

E-mail: bw.kaplon@poczta.onet.pl
Copyright: © 2013 Jan Kochanowski University in Kielce This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
© 2024 Termedia Sp. z o.o.
Developed by Bentus.