Summary Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate ...whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0–3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov , number NCT00403767. Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio HR 0·94, 95% CI 0·77–1·16) and those without (1·44% vs 1·88%; 0·77, 0·58–1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87–1·07) and those without (16·69% vs 15·19%; 1·10, 0·99–1·21; interaction p=0·08). Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. Funding Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.
Objectives This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. Background There ...are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. Methods We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Results Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 n = 161 in the warfarin arm, 1.46 n = 160 in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio HR: 1.38; 95% confidence interval CI: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Conclusions Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation ROCKET AF; NCT00403767 )
Background The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in ...patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. Methods We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non–central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. Results The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio HR 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. Conclusions and Relevance The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.
Abstract We investigated stroke outcomes in normal weight (body mass index BMI 18.50-24.99 kg/m2 ), overweight (BMI 25.00-29.99 kg/m2 ), and obese (BMI ≥30 kg/m2 ) patients with AF treated with ...rivaroxaban and warfarin. We compared the incidence of stroke and systemic embolic events (SEE) as well as bleeding events in normal weight (n=3289), overweight (n=5535), and obese (n=5206) patients in a post-hoc analysis of the ROCKET AF trial. Stroke and SEE rates per 100 patient-years were 2.93 in the normal weight group (reference group), 2.28 in the overweight group (adjusted hazard ratio HR 0.81, 95% confidence interval CI: 0.66-0.99, p=0.04), and 1.88 in the obese group (adjusted HR 0.69, 95% CI: 0.55-0.86, p<0.001). The risk of stroke was statistically significantly lower for obese patients with BMI ≥35 compared with normal weight patients in both the rivaroxaban and warfarin groups (rivaroxaban: HR 0.62, 95% CI: 0.40-0.96, p=0.033; warfarin: HR 0.48, 95% CI: 0.31-0.74, p<0.001). In conclusion, among patients with AF treated with anticoagulant therapy, increased BMI was associated with decreased stroke risk. Warfarin and the novel anticoagulant rivaroxoban are effective in stroke prevention in all sub-groups of obese patients.
Recent evidence suggests that cardiac sarcoidosis (CS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) can manifest very similarly.
To investigate whether there are significant demographic ...and electrophysiological differences between patients with CS and ARVC.
We prospectively compared patients with proven CS or ARVC who underwent radiofrequency catheter ablation of ventricular tachycardias by using 3-dimensional electroanatomical mapping. Furthermore, we evaluated whether the diagnostic criteria for ARVC would have excluded ARVC in patients with CS.
Eighteen patients (13 men; mean age 44.9 years) were included. All 18 patients had mild to moderately reduced right ventricular ejection fraction. Patients with cardiac sarcoidosis (n = 8) had a significantly lower mean left ventricular ejection fraction (35.6±19.3 vs 60.6±9.4; P = .002). Patients with CS had a significantly wider QRS (0.146 vs 0.110s; P = .004). Five of 8 (63%) patients with CS fulfilled the diagnostic ARVC criteria. Ventricular tachycardias (VTs) with a left bundle branch block pattern were documented in all but one patient (with CS). Programmed ventricular stimulation induced an average of 3.7 different monomorphic VTs in patients with CS vs 1.8 in patients with ARVC (P = .01). VT significantly more often originated in the apical region of the right ventricle in CS vs ARVC (P = .001), with no other predilection sites. Ablation success and other electrophysiological parameters were not different.
The current diagnostic ARVC guidelines do not reliably exclude patients with CS. Clinical and electrophysiological parameters that were characteristic of CS in our patients include reduced left ventricular ejection fraction, a significantly wider QRS, right-sided apical VT, and more inducible forms of monomorphic VT.
Background We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in ROCKET AF; in particular, those with known coronary artery disease (CAD). Methods ...Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction (MI), death, and major or non-major clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors. Results A total of 5205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2 mg), 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior MI (22% vs. 14%; p < 0.001) and heart failure (68% vs. 59%; p < 0.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (p = 0.95 for interaction), and major or NMCR bleeding (p = 0.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (HR 1.16, 95% CI 0.98–1.37; p = 0.094), but higher rates of all-cause death (HR 1.27, 95% CI 1.13–1.42; p < 0.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21–1.43; p < 0.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (p = 0.009). Conclusion Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF.
Introduction Paroxysmal atrial fibrillation (AF) may progress to persistent AF. We studied the clinical correlates and the effect of rhythm-control strategy on AF progression. Methods RecordAF was a ...worldwide prospective survey of AF management. Consecutive eligible patients with recent-onset AF were included and allocated to rate or rhythm control according to patient/physician choice. A total of 2,137 patients were followed up for 12 months. Atrial fibrillation progression was defined as a change from paroxysmal to persistent/permanent AF. Results Progression of AF occurred in 318 patients (15%) after 1 year. Patients with AF progression were older; had a higher diastolic blood pressure; and more often had a history of coronary artery disease, stroke or transient ischemic attack, hypertension, or heart failure. Patients treated with rhythm control were less likely to show progression than those treated only with rate control (164/1542 11% vs 154/595 26%, P < .001). Multivariable analysis showed that history of heart failure (odds ratio OR 2.2, 95% CI 1.7-2.9, P < .0001), history of hypertension (OR 1.5, 95% CI 1.1-2.0, P = .01), and rate control rather than rhythm control (OR 3.2, 95% CI 2.5-4.1, P < .0001) were independent predictors of AF progression. The propensity score–adjusted OR of AF progression in patients with rate rather than rhythm control was 3.3 (95% CI 2.4-4.6, P < .0001). Conclusions Although heart failure and hypertension are associated with AF progression, rhythm control is associated with lower risk of AF progression.
The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation (RecordAF) is the first worldwide, 1-year observational, longitudinal study of the management of ...paroxysmal/persistent atrial fibrillation (AF) in recently diagnosed patients. The study was conducted at 532 sites in 21 countries across Europe, America, and Asia; recruitment was completed in April 2008. The primary objectives were to prospectively assess the therapeutic success and clinical outcomes in rhythm- and rate-control strategies. The study design and patient baseline data are reported. A total of 5,814 patients with AF were registered, and 5,604 were eligible for evaluation. Rhythm- and rate-control strategies were applied to 55% and 45% of patients, respectively, at study inclusion. Rhythm-control patients mainly received class III agents (45%) or β blockers (51%), except for sotalol, and rate-control patients mainly received β blockers (72%), except for sotalol, or cardiac glycosides (34%). Patients receiving a rhythm-control strategy were younger, had a lower resting heart rate, were more frequently symptomatic, and were more likely to have recently diagnosed AF or paroxysmal AF compared to patients receiving a rate-control strategy. A rate-control strategy was more common in patients with a history of heart failure or valvular heart disease and persistent AF. Rate-control patients more often had previous electrocardiographic evidence of AF and were not in sinus rhythm at inclusion (p <0.01 for both end points). Patients were followed at 6 and 12 months, and changes in therapeutic strategy and clinical outcomes were recorded. In conclusion, the RecordAF study results will provide a global perspective on current AF treatment strategies.
Background We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF). ...Methods The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP. Results In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10 mm Hg increase in screening SBP (hazard ratio HR 1.07, 95% CI confidence interval CI 1.02–1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89–1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03–1.95) (P=0.06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P-interaction=0.69). Conclusions In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin was consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF.
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