ROCKET AF: rivaroxaban for stroke prevention in atrial fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and it markedly increases the risk of stroke^{98, 87}
Additional risk factors such as age, gender and concomitant medical conditions (including heart failure and diabetes mellitus) further exacerbate the risk of stroke^{99, 100, 101}
Vitamin K antagonists, such as warfarin and acenocoumarol, are the current standard of care for stroke prevention in AF but are challenging to manage in clinical practice¹⁰²
Although effective, vitamin K antagonists have an unpredictable pharmacological profile that necessitates routine coagulation monitoring and dose adjustment to ensure that patients remain within the therapeutic range³⁰
- Despite guidelines, less than 55% of patients with AF who need anticoagulation receive it⁷²
- Only 1 in 10 patients with AF is adequately anticoagulated at the time of first stroke¹⁰³

ROCKET AF: once-daily rivaroxaban versus dose-adjusted warfarin

ROCKET AF compared the efficacy and safety of once-daily rivaroxaban with warfarin for the prevention of stroke and systemic embolism in patients with non-valvular AF for whom guidelines recommend oral anticoagulation.⁷⁴

Objective

The main objective of ROCKET AF was to determine if once-daily rivaroxaban was as effective as dose-adjusted warfarin for the prevention of thromboembolic events in patients with non-valvular AF who are at increased risk of stroke.

Study design

ROCKET AF was a prospective, randomized, double-blind, multicentre, parallel-group, active-control, event-driven study of 14,264 patients with non-valvular AF and a history of stroke, TIA or systemic embolism or with at least two risk factors for stroke.. The patients were randomized to receive either:

Rivaroxaban 20 mg once-daily (15 mg once-daily for patients with moderate renal impairment at entry [creatinine clearance of 30–49 ml/min])
Warfarin titrated to an international normalized ratio of 2.5 (range 2.0–3.0)

To preserve blinding, all groups underwent routine coagulation monitoring as required with warfarin. Sham international normalized ratio values were provided for patients receiving rivaroxaban.⁷⁵

Inclusion criteria

The study was designed to evaluate a moderate-to-high risk adult patient population with persistent or paroxysmal AF and either:

Prior stroke, transient ischaemic attack or systemic embolism; or
Two or more risk factors for stroke including: clinical heart failure and/or left ventricular ejection fraction ≤35%, hypertension, age ≥75 years or diabetes mellitus
Patients with only two risk factors for stroke were capped at 10% of the overall trial population, with the remaining patients requiring three or more risk factors, or a prior stroke, transient ischaemic attack or systemic embolism

Study endpoints⁷⁴

The primary efficacy endpoint was the composite endpoint of stroke (ischaemic or haemorrhagic) and systemic embolism
The principal safety outcome was the composite of major and non-major clinically relevant bleeding

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Article references

98 - National Heart Lung and Blood Institute. Atrial Fibrillation. 2009. Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/af/af_what.html [accessed 24 August 2011].
87 - Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983–988.
99 - Go AS, Hylek EM, Phillips KA et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370–2375.
100 - Heeringa J, van der Kuip DAM, Hofman A et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006;27:949–953.
101 - Benjamin EJ, Levy D, Vaziri SM et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 1994;271:840–844.
102 - Verheugt FW. The new oral anticoagulants. Neth Heart J 2010;18:314–318.
30 - Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):160S-198S.
72 - Gladstone DJ, Bui E, Fang J et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009;40:235–240.
103 - Waldo AL, Becker RC, Tapson VF et al. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol 2005;46:1729–1736.
74 - The Executive Steering Committee on behalf of the 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.
75 - Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–891.

Atrial fibrillation: A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
Efficacy: The ability of a drug to produce the desired effect.
International Normalized Ratio: A system for assessing the clotting tendency of blood in patients receiving anticoagulant therapy. For patients with atrial fibrillation, the recommended target INR range is between 2 and 3. If the INR is higher than 3, patients are at risk of serious bleeding. If the INR is less than 2, patients are at risk of a blood clotting event.
Composite endpoint: A combination of two or more endpoints in a clinical trial.

ROCKET AF: rivaroxaban for stroke prevention in atrial fibrillation