Dataset Information

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

ABSTRACT:

Background

Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions.

Methods and results

In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS2 score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P<0.0001) and age ?75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P<0.0001) were associated with higher all-cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C-index 0.677).

Conclusions

In a large population of patients anticoagulated for nonvalvular atrial fibrillation, ?7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.

Clinical trial registration

URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

SUBMITTER: Pokorney SD

PROVIDER: S-EPMC4943233 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

Pokorney Sean D SD Piccini Jonathan P JP Stevens Susanna R SR Patel Manesh R MR Pieper Karen S KS Halperin Jonathan L JL Breithardt Günter G Singer Daniel E DE Hankey Graeme J GJ Hacke Werner W Becker Richard C RC Berkowitz Scott D SD Nessel Christopher C CC Mahaffey Kenneth W KW Fox Keith A A KA Califf Robert M RM

Journal of the American Heart Association 20160308 3

<h4>Background</h4>Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions.<h4>Methods and results</h4>In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfar ...[more]

PMID: 26955859

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Project description:Background The ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) evaluated rivaroxaban (20/15 mg/d) versus warfarin in patients with atrial fibrillation. A separate trial, J-ROCKET AF (Japanese ROCKET AF), compared rivaroxaban (15/10 mg/d) and warfarin in Japanese patients with atrial fibrillation. Data about rivaroxaban following J-ROCKET AF criteria compared with warfarin and ROCKET AF dosage were limited. Methods and Results This retrospective study used medical data from a multicenter healthcare provider in Taiwan that included 3162 patients taking rivaroxaban. Among 2320 patients with an estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m2, 384 and 1936 patients followed the ROCKET AF (20 mg/d) and J-ROCKET AF (15 mg/d) recommendation, respectively. Among 842 patients with an eGFR <50 mL/min per 1.73 m2, 422 and 420 patients followed the ROCKET AF (15 mg/d) and J-ROCKET AF (10 mg/d) recommendation, respectively. A total of 2053 patients with atrial fibrillation receiving warfarin were identified. Rivaroxaban following either ROCKET AF or J-ROCKET AF dosage criteria was associated with a comparable risk of thromboembolism but a lower risk of bleeding than warfarin. For patients with an eGFR ≥50 mL/min per 1.73 m2, risks of clinical events did not differ significantly between the 2 dosage criteria of rivaroxaban. For patients with an eGFR <50 mL/min per 1.73 m2, the ROCKET AF dosage was associated with a higher risk of major bleeding compared with the J-ROCKET AF dosage (hazard ratio, 2.70; P=0.0445) without significant differences regarding the risk of ischemic events. Conclusions In Asian patients with atrial fibrillation, the J-ROCKET AF dosage was as effective as the ROCKET AF dosage irrespective of renal function. The risk of major bleeding was lower with the J-ROCKET AF dosage in patients with an eGFR <50 mL/min per 1.73 m2. Compared with warfarin, rivaroxaban following either dosage criteria was effective and even safer.

Project description:BackgroundReduced-dose rivaroxaban (10 mg) was used in the J-ROCKET AF trial, demonstrating safety in the Asian population. It remains unclear whether treatment with reduced-dose versus full-dose rivaroxaban (20 mg/15 mg) is associated with all-cause mortality in older patients with nonvalvular atrial fibrillation. Proposed: To evaluate the effects of reduced-dose rivaroxaban on all-cause mortality in patients over 85.MethodsWe retrospectively enrolled medical records representing the period from October 2012 to November 2016. The 2 × 2 factorial design incorporated age (≥85 vs. <85) and rivaroxaban use (reduced vs. full dose). The primary study outcomes were all-cause and cardiac-related mortality.ResultsThe study enrolled 2386 patients with a mean age of 76.6 ± 10.4 years; 51.8% were male. In the ≥85 group (n = 593), the reduced-dose subgroup had lower all-cause (5.3% vs. 10.6%, p = 0.02) and cardiac-related mortality (1.9% vs. 5.1%, p = 0.04), whereas the younger patients receiving reduced-dose rivaroxaban had higher all-cause mortality (3.7% vs. 1.8%, p = 0.01) but no difference in cardiac-related mortality (1.2% vs. 0.7%, p = 0.33). The rate of hospitalization for heart failure was significantly lower in the elderly group with reduced-dose rivaroxaban (7.2% vs. 15.7%, p < 0.01) but not in the younger group. After adjusting for confounders in the older group, treatment with reduced-dose rivaroxaban was associated with lower risk of all-cause mortality (adjusted HR (aHR): 0.40, 95% CI: 0.21-0.74, p < 0.01) and hospitalization for heart failure (aHR: 0.54, 95% CI: 0.29-0.99, p = 0.05). No associations were found between rivaroxaban dose and cardiac-related mortality in either group, nor between younger age and any outcome.ConclusionsReduced-dose rivaroxaban was associated with lower risks of all-cause mortality and hospitalization for heart failure in older patients with nonvalvular atrial fibrillation. Future studies can investigate the effect of reduced-dose rivaroxaban on prognoses in elderly individuals ≥85 years in the west.

Project description:Background Patients with atrial fibrillation (AF) treated with oral anticoagulants may be exposed to an increased risk of bleeding events. The HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INRs, Elderly, Drugs or alcohol) score is a simple, well-established, clinical bleeding-risk prediction score. Recently, a new algorithm-based score was proposed, the GARFIELD-AF (Global Anticoagulant in the Field-AF) bleeding score. We compared HAS-BLED and GARFIELD-AF scores in predicting adjudicated bleeding events in a clinical trial cohort of patients with AF taking anticoagulants, in the first external comparative validation of both scores. Methods and Results We analyzed patients from the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Patients With AF) III and V trials. All patients assigned to the warfarin arm with information to calculate the scores were considered. Outcomes were major, major/clinically relevant nonmajor, and any bleeding. A total of 3550 warfarin-treated patients were available for analysis. Of these patients, 2519 (71.0%) had a HAS-BLED score ≥3, whereas based on GARFIELD-AF median value, 2056 (57.9%) were categorized as "high score." Both HAS-BLED and GARFIELD-AF C-indexes showed modest predictive value (C-index [95% confidence interval] for major bleeding, 0.58 [0.56-0.60] and 0.56 [0.54-0.57], respectively); however, GARFIELD-AF was not predictive of any bleeding. The GARFIELD-AF bleeding score had a significantly lower sensitivity and a negative reclassification for any bleeding compared with HAS-BLED, assessed by integrated discrimination improvement and net reclassification improvement (both P<0.001). HAS-BLED showed a 5% net benefit for any bleeding occurrence. Conclusions The algorithm-based GARFIELD-AF bleeding score did not show any significant improvement in major and major/clinically relevant nonmajor prediction compared with the simple HAS-BLED score. For clinical usefulness in prediction of any bleeding, the HAS-BLED score showed a significant net benefit compared with the GARFIELD-AF.

Project description:BackgroundAntiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment.ObjectiveTo study the use and outcomes of AAD therapy in anticoagulated patients with AF.MethodsPatients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin).ResultsOf 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; Pinteraction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; Pinteraction = .33).ConclusionTreatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.

Project description:ObjectivesWe identified factors associated with thromboembolic and bleeding events in two contemporary cohorts of anticoagulated patients with atrial fibrillation (AF), treated with either vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs).DesignProspective, multicentre observational study.Setting461 centres in seven European countries.Participants5310 patients receiving a VKA (PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), derivation cohort) and 3156 patients receiving a NOAC (PREFER in AF Prolongation, validation cohort) for stroke prevention in AF.Outcome measuresRisk factors for thromboembolic events (ischaemic stroke, systemic embolism) and major bleeding (gastrointestinal bleeding, intracerebral haemorrhage and other life-threatening bleeding).ResultsThe mean age of patients enrolled in the PREFER in AF registry was 72±10 years, 40% were female and the mean CHA2DS2-VASc Score was 3.5±1.7. The incidence of thromboembolic and major bleeding events was 2.34% (95% CI 1.93% to 2.74%) and 2.84% (95% CI 2.41% to 3.33%) after 1-year of follow-up, respectively.Abnormal liver function, prior stroke or transient ischaemic attack, labile international normalised ratio (INR), concomitant therapy with antiplatelet or non-steroidal anti-inflammatory drugs, heart failure and older age (≥75 years) were independently associated with both thromboembolic and major bleeding events.With the exception of unstable INR values, these risk factors were validated in patients treated with NOACs (PREFER in AF Prolongation Study, 72±9 years, 40% female, CHA2DS2-VASc 3.3±1.6). For each single point decrease on a modifiable bleeding risk scale we observed a 30% lower risk for major bleeding events (OR 0.70, 95% CI 0.64 to 0.76, p<0.01) and a 28% lower rate of thromboembolic events (OR 0.72, 95% CI 0.66 to 0.82, p<0.01).ConclusionAttending to modifiable risk factors is an important treatment target in anticoagulated AF patients to reduce thromboembolic and bleeding events. Initiation of anticoagulation in those at risk of stroke should not be prevented by elevated bleeding risk scores.

Dataset Information

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

Background

Methods and results

Conclusions

Clinical trial registration

Publications

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

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