title: Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.
abstract: OBJECTIVE
  Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm.
  
  
  RESULTS
  ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037).
  
  
  CONCLUSIONS
  Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Box 3126, Durham, NC, USA.
authors.forename: William Schuyler
authors.initials: WS
authors.lastname: Jones
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.forename: Jonathan
authors.initials: J
authors.lastname: Halperin
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Gunter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications*; D004311:Double-Blind Method; D004617:Embolism / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D058729:Peripheral Arterial Disease / Q000150:complications*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D009025:Morpholines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D014859:Warfarin; D000069552:Rivaroxaban
keywords: Atrial fibrillation; Bleeding; Peripheral artery disease; Rivaroxaban; Stroke; Systemic embolism