Videos from the Patient-Centered Outcomes Research Institute on the prevention of stroke in patients with atrial fibrillation.
IMPORTANCE:
Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment.
OBJECTIVES:
To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk.
DESIGN, SETTING, AND PARTICIPANTS:
Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015.
EXPOSURES:
Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy.
MAIN OUTCOMES AND MEASURES:
Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10 000 person-years of anticoagulant treatment, incidence rate ratios (IRRs).
RESULTS:
There were 1 643 123 patients with 1 713 183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651 427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870 330 person-years [74.9%]). During 754 389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10 000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10 000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10 000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10 000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10 000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]).
CONCLUSIONS AND RELEVANCE:
Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.
Abstract
Catheter ablation (CA) of atrial fibrillation (AF) is currently one of the most commonly performed electrophysiology procedures. Ablation of paroxysmal AF is based on the elimination of triggers by pulmonary vein isolation (PVI), while different strategies for additional AF substrate modification on top of PVI have been proposed for ablation of persistent AF. Nowadays, various technologies for AF ablation are available. The radiofrequency point-by-point ablation navigated by electro-anatomical mapping system and cryo-balloon technology are comparable in terms of the efficacy and safety of the PVI procedure. Long-term success of AF ablation including multiple procedures varies from 50 to 80%. Arrhythmia recurrences commonly occur, mostly due to PV reconnection. The recurrences are particularly common in patients with non-paroxysmal AF, dilated left atrium and the "early recurrence" of AF within the first 2–3 post-procedural months. In addition, this complex procedure can be accompanied by serious complications, such as cardiac tamponade, stroke, atrio-esophageal fistula and PV stenosis. Therefore, CA represents a second-line treatment option after a trial of antiarrhythmic drug(s). Good candidates for the procedure are relatively younger patients with symptomatic and frequent episodes of AF, with no significant structural heart disease and no significant left atrial enlargement. Randomized trials demonstrated the superiority of ablation compared to antiarrhythmic drugs in terms of improving the quality of life and symptoms in AF patients. However, nonrandomized studies reported additional clinical benefits from ablation over drug therapy in selected AF patients, such as the reduction of the mortality and stroke rates and the recovery of tachyarrhythmia-induced cardiomyopathy. Future research should enable the creation of more durable ablative lesions and the selection of the optimal lesion set in each patient according to the degree of atrial remodeling. This could provide better long-term CA success and expand indications for the procedure, especially among the patients with non-paroxysmal AF.
Purpose
To review the evidence and provide clinical recommendations for the pharmacologic management of atrial fibrillation.
Methods
This guideline is based on two systematic reviews of published randomized controlled trials (RCTs) and prospective and retrospective observational studies from 2000 to 2012. An updated literature search was performed to identify new studies from 2012 to December 31, 2015. The target audience for the guideline includes all primary care clinicians, and the target patient population includes adults who have nonvalvular atrial fibrillation that is not due to a reversible cause. This guideline was developed using a modified version of GRADE to evaluate the quality of the evidence and make recommendations based on the balance of benefits and harms.
Purpose of Review
To update a previous review in patients with atrial fibrillation/atrial flutter (AF) to determine the best assessment tools for predicting risk of stroke and bleeding, as well as the best treatment options to prevent stroke. Current treatments include new antithrombotic strategies, devices, and oral anticoagulants (oral direct thrombin inhibitors, factor Xa inhibitors).
Key Messages
Structured Abstract
Objectives. This review updates previous reviews regarding the optimal risk stratification tools for stroke and bleeding prediction, and treatment options for stroke prevention in patients with atrial fibrillation.
Data sources. We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language comparative studies published from January 1, 2000, to February 14, 2018.
Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. When possible, random-effects models were used to compute summary estimates of effects.
Results. Our review included 320 articles (185 unique studies). This included 61 studies relevant to predicting thromboembolic risk, 38 relevant to predicting bleeding risk, and 117 relevant to interventions for preventing thromboembolic (TE) events. Data suggest that the CHADS2, CHA2DS2-VASc, and ABC risk scores have the best evidence predicting TE risk (moderate strength of evidence [SOE] for limited prediction ability of each score) and that the HAS-BLED score has the best evidence to predict bleeding risk (moderate SOE).
We found that a thrombin inhibitor (dabigatran 150 mg) was superior to warfarin in preventing stroke (including hemorrhagic) or systemic embolism (relative risk [RR] 0.66; 95% confidence interval [CI] 0.53 to 0.82), with no statistically significant difference in the occurrence of major bleeding (RR 0.93; 95% CI 0.81 to 1.07) (high SOE for both outcomes). The Xa inhibitor apixaban was superior to warfarin in preventing stroke or systemic embolism (hazard ratio [HR] 0.79; 95% CI 0.66 to 0.95; high SOE), major bleeding (HR 0.69; 95% CI 0.60 to 0.80; high SOE), and all-cause mortality (HR 0.89; 95% CI 0.80 to 0.998; low SOE). Apixaban was also superior to aspirin in preventing stroke or systemic embolism (HR 0.45; 95% CI 0.32 to 0.62), with similar risk for major bleeding (HR 1.13; 95% CI 0.74 to 1.75) in patients who are not suitable for warfarin (moderate SOE for both outcomes). The Xa inhibitor edoxaban reduced hemorrhagic stroke and major bleeding compared to warfarin (moderate SOE for both outcomes) but had no evidence of a difference in stroke or systemic embolism (moderate SOE) or myocardial infarction (moderate SOE). The Xa inhibitor rivaroxaban was similar to warfarin in preventing stroke or systemic embolism (HR 0.88, 95% CI 0.74 to 1.03; moderate SOE), with similar rates of major bleeding (low SOE) and death (moderate SOE). Low SOE for major bleeding was due to a trend toward an increase in risk of major bleeding with rivaroxaban seen in observational studies. Comparative effectiveness findings for stroke prevention were limited by the direct comparisons between individual direct oral anticoagulants. Evidence regarding nonpharmacologic interventions was sparse, but left atrial appendage (LAA) closure devices showed a trend toward benefit over warfarin for strokes, major bleeding, and all-cause mortality that did not reach statistical significance. Higher adverse events (excessive bleeding or procedure-related complications) were observed with LAA (low SOE).
Conclusions. Overall, we found that CHADS2, CHA2DS2-VASc, and ABC scores have similar evidence regarding their ability to predict stroke risk in patients with atrial fibrillation, whereas HAS-BLED has the best evidence to predict bleeding risk. Direct oral anticoagulants (specifically apixaban and dabigatran) demonstrate reductions in stroke events and reductions (apixaban) or similar (dabigatran) rates in bleeding events when compared with warfarin, while rivaroxaban was similar in both benefits and harms to warfarin. Edoxaban reduced hemorrhagic stroke and major bleeding compared to warfarin but had no evidence of a difference in other outcomes. More studies are needed directly comparing oral anticoagulants, including thrombin inhibitors and individual Xa inhibitors.
