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1.
N Engl J Med ; 390(2): 107-117, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-37952132

RESUMEN

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).


Asunto(s)
Anticoagulantes , Aspirina , Fibrilación Atrial , Embolia , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Canadá , Embolia/etiología , Embolia/prevención & control , Hemorragia/inducido químicamente , Piridonas/efectos adversos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Método Doble Ciego
2.
Circulation ; 147(23): 1748-1757, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37042255

RESUMEN

BACKGROUND: There is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction. METHODS: Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY [Randomized Evaluation of Long-term Anticoagulation Therapy], 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], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), we performed an individual patient-level network meta-analysis to evaluate the safety and efficacy of DOACs versus warfarin across continuous creatinine clearance (CrCl). A multivariable Cox model including treatment-by-CrCl interaction with random effects was fitted to estimate hazard ratios for paired treatment strategies (standard-dose DOAC, lower-dose DOAC, and warfarin). Outcomes included stroke and systemic embolism (S/SE), major bleeding, intracranial hemorrhage (ICH), and death. RESULTS: Among 71 683 patients (mean age, 70.6±9.4 years; 37.3% female; median follow-up, 23.1 months), the mean CrCl was 75.5±30.5 mL/min. The incidence of S/SE, major bleeding, ICH, and death increased significantly with worsening kidney function. Across continuous CrCl values down to 25 mL/min, the hazard of major bleeding did not change for patients randomized to standard-dose DOACs compared with those randomized to warfarin (Pinteraction=0.61). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of ICH at CrCl values <122 mL/min, with a trend for increased safety with DOAC as CrCl decreased (6.2% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of S/SE with CrCl <87 mL/min, with a significant treatment-by-CrCl effect (4.8% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.01). The hazard of death was significantly lower with standard-dose DOACs for patients with CrCl <77 mL/min, with a trend toward increasing benefit with lower CrCl (2.1% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Use of lower-dose rather than standard-dose DOACs was not associated with a significant difference in incident bleeding or ICH in patients with reduced kidney function but was associated with a higher incidence4 of death and S/SE. CONCLUSIONS: Standard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death. These findings support the use of standard-dose DOACs over warfarin in patients with kidney dysfunction.


Asunto(s)
Fibrilación Atrial , Embolia , Accidente Cerebrovascular , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Warfarina/efectos adversos , Metaanálisis en Red , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Factor Xa , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/epidemiología , Hemorragia/epidemiología , Hemorragias Intracraneales/inducido químicamente , Embolia/epidemiología , Riñón , Administración Oral , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Eur Heart J ; 44(20): 1807-1814, 2023 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-37038327

RESUMEN

AIMS: The prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation. METHODS AND RESULTS: Individual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%-8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%-14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%-7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%-8.9%). CONCLUSION: Patients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Administración Oral , Anticoagulantes , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Accidente Cerebrovascular Isquémico/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento
4.
Circulation ; 145(4): 242-255, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34985309

RESUMEN

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data. METHODS: We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], 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], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex. RESULTS: A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin. CONCLUSIONS: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.


Asunto(s)
Anticoagulantes/uso terapéutico , Warfarina/uso terapéutico , Administración Oral , Factores de Edad , Anciano , Anticoagulantes/farmacología , Femenino , Humanos , Masculino , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores Sexuales , Warfarina/farmacología
5.
Am Heart J ; 265: 132-136, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37506747

RESUMEN

Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00412984).

6.
Europace ; 25(3): 845-854, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36758013

RESUMEN

AIMS: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. METHODS AND RESULTS: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or permanent SR (defined as ≥6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). CONCLUSION: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling. CLINICAL TRIAL REGISTRATION: NCT00174785.


Asunto(s)
Amiodarona , Fibrilación Atrial , Aleteo Atrial , Humanos , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Aleteo Atrial/diagnóstico , Aleteo Atrial/tratamiento farmacológico , Aleteo Atrial/epidemiología , Dronedarona/efectos adversos , Hospitalización
7.
Europace ; 24(11): 1754-1762, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-34374766

RESUMEN

AIMS: Age and sex may impact the efficacy of antiarrhythmic drugs on cardiovascular outcomes and arrhythmia recurrences in patients with atrial fibrillation (AF). We report on a post hoc analysis of the ATHENA study (NCT00174785), which examined cardiovascular outcomes in patients with non-permanent AF treated with dronedarone vs. placebo. METHODS AND RESULTS: Efficacy and safety of dronedarone were assessed in patients according to age and sex. Baseline characteristics were comparable across subgroups, except for cardiovascular comorbidities, which were more frequent with increasing age. Dronedarone significantly reduced the risk of cardiovascular hospitalization or death due to any cause among patients 65-74 [n = 1830; hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.60-0.83; P < 0.0001] and ≥75 (n = 1925; HR 0.75, 95% CI 0.65-0.88; P = 0.0002) years old and among males (n = 2459; HR 0.74, 95% CI 0.64-0.84; P < 0.00001) and females (n = 2169; HR 0.77, 95% CI 0.67-0.89; P = 0.0002); outcomes were similar for time to AF/AFL recurrence. Among patients aged <65 years (n = 873), cardiovascular hospitalization or death due to any cause with dronedarone vs. placebo was associated with an HR of 0.89 (95% CI 0.71-1.11; P = 0.3). The incidence of all treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation was comparable among males and females, and increased with increasing age. CONCLUSIONS: These results support the use of dronedarone for the improvement of clinical outcomes among patients aged ≥65 years and regardless of sex.


Asunto(s)
Amiodarona , Fibrilación Atrial , Aleteo Atrial , Femenino , Humanos , Recién Nacido , Masculino , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Aleteo Atrial/diagnóstico , Aleteo Atrial/tratamiento farmacológico , Dronedarona/efectos adversos
8.
Europace ; 24(7): 1058-1064, 2022 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-35061877

RESUMEN

AIMS: There is uncertainty about whether and how to perform screening for atrial fibrillation (AF). To estimate the incidence of previously undetected AF that would be captured using a continuous 14-day ECG monitor and the associated risk of stroke. METHODS AND RESULTS: We analysed data from a cohort of patients >65 years old with hypertension and a pacemaker, but without known AF. For each participant, we simulated 1000 ECG monitors by randomly selecting 14-day windows in the 6 months following enrolment and calculated the average AF burden (total time in AF). We used Cox proportional hazards models adjusted for CHA2DS2-VASc score to estimate the risk of subsequent ischaemic stroke or systemic embolism (SSE) associated with burdens of AF > and <6 min. Among 2470 participants, the median CHA2DS2-VASc score was 4.0, and 44 patients experienced SSE after 6 months following enrolment. The proportion of participants with an AF burden >6 min was 3.10% (95% CI 2.53-3.72). This was consistent across strata of age and CHA2DS2-VASc scores. Over a mean follow-up of 2.4 years, the rate of SSE among patients with <6 min of AF was 0.70%/year, compared to 2.18%/year (adjusted HR 3.02; 95% CI 1.39-6.56) in those with >6 min of AF. CONCLUSIONS: Approximately 3% of individuals aged >65 years with hypertension may have more than 6 min of AF detected by a 14-day ECG monitor. This is associated with a stroke risk of over 2% per year. Whether oral anticoagulation will reduce stroke in these patients is unknown.


Asunto(s)
Fibrilación Atrial , Isquemia Encefálica , Hipertensión , Accidente Cerebrovascular , Anciano , Anticoagulantes , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Isquemia Encefálica/diagnóstico , Electrocardiografía , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Incidencia , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología
9.
Circulation ; 141(17): 1384-1392, 2020 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-32160801

RESUMEN

BACKGROUND: Compared with the general population, patients with advanced chronic kidney disease have a >10-fold higher burden of atrial fibrillation. Limited data are available guiding the use of nonvitamin K antagonist oral anticoagulants in this population. METHODS: We compared the safety of apixaban with warfarin in 269 patients with atrial fibrillation and advanced chronic kidney disease (defined as creatinine clearance [CrCl] 25 to 30 mL/min) enrolled in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). Cox proportional models were used to estimate hazard ratios for major bleeding and major or clinically relevant nonmajor bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using nonlinear mixed effects models. RESULTS: Among patients with CrCl 25 to 30 mL/min, apixaban caused less major bleeding (hazard ratio, 0.34 [95% CI, 0.14-0.80]) and major or clinically relevant nonmajor bleeding (hazard ratio, 0.35 [95% CI, 0.17-0.72]) compared with warfarin. Patients with CrCl 25 to 30 mL/min randomized to apixaban demonstrated a trend toward lower rates of major bleeding when compared with those with CrCl >30 mL/min (P interaction=0.08) and major or clinically relevant nonmajor bleeding (P interaction=0.05). Median daily steady-state areas under the curve for apixaban 5 mg twice daily were 5512 ng/(mL·h) and 3406 ng/(mL·h) for patients with CrCl 25 to 30 mL/min or >30 mL/min, respectively. For apixaban 2.5 mg twice daily, the median exposure was 2780 ng/(mL·h) for patients with CrCl 25 to 30 mL/min. The area under the curve values for patients with CrCl 25 to 30 mL/min fell within the ranges demonstrated for patients with CrCl >30 mL/min. CONCLUSIONS: Among patients with atrial fibrillation and CrCl 25 to 30 mL/min, apixaban caused less bleeding than warfarin, with even greater reductions in bleeding than in patients with CrCl >30 mL/min. We observed substantial overlap in the range of exposure to apixaban 5 mg twice daily for patients with or without advanced chronic kidney disease, supporting conventional dosing in patients with CrCl 25 to 30 mL/min. Randomized, controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced chronic kidney disease, including those receiving dialysis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.


Asunto(s)
Anticoagulantes , Fibrilación Atrial , Pirazoles , Piridonas , Warfarina , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinética , Fibrilación Atrial/sangre , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Método Doble Ciego , Femenino , Hemorragia/sangre , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Masculino , Modelos de Riesgos Proporcionales , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirazoles/farmacocinética , Piridonas/administración & dosificación , Piridonas/efectos adversos , Piridonas/farmacocinética , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Warfarina/administración & dosificación , Warfarina/efectos adversos , Warfarina/farmacocinética
10.
Stroke ; 52(8): 2715-2722, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34192898

RESUMEN

Occult atrial fibrillation (AF) is a leading cause of stroke of unclear cause. The optimal approach to secondary stroke prevention for these patients remains elusive. The term embolic stroke of undetermined source (ESUS) was coined to describe ischemic strokes in which the radiographic features demonstrate territorial infarcts resembling those seen in patients with confirmed sources of embolism but without a clear source of embolism detected. It was assumed that patients with ESUS had a high rate of occult AF and would benefit from treatment with direct oral anticoagulants, which are at least as effective as vitamin K antagonists for secondary stroke prevention in patients with AF, but with a much lower risk of intracerebral hemorrhage. Two recent large randomized trials failed to show superiority of direct oral anticoagulants over aspirin in ESUS patients. These findings prompt a reexamination of the ESUS concept, with the goal of improving specificity for detecting patients with a cardioembolic cause. Based on the negative trial results, there is renewed interest in the role of long-term cardiac monitoring for AF in patients who fit the current ESUS definition, as well as the clinical implication of detecting AF. Ongoing trials are exploring these questions. Current ESUS definitions do not accurately detect the patients who should be prescribed direct oral anticoagulants, potentially because occult AF is less common than expected in these patients and/or anticoagulants may be less beneficial in patients with ESUS but no AF than they are for patients with stroke with established AF. More specific criteria to identify patients who may be at higher risk for occult AF and reduce their risk of subsequent stroke have been developed and are being tested in ongoing clinical trials.


Asunto(s)
Terapia Antiplaquetaria Doble/métodos , Accidente Cerebrovascular Embólico/tratamiento farmacológico , Accidente Cerebrovascular Embólico/etiología , Prevención Secundaria/métodos , Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Fibrilación Atrial/sangre , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Hemorragia Cerebral/sangre , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Ensayos Clínicos como Asunto/métodos , Accidente Cerebrovascular Embólico/sangre , Inhibidores del Factor Xa/administración & dosificación , Humanos , Embolia Intracraneal/sangre , Embolia Intracraneal/complicaciones , Embolia Intracraneal/tratamiento farmacológico , Rivaroxabán/administración & dosificación
11.
Am Heart J ; 233: 48-58, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33296688

RESUMEN

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date. DESIGN: COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771). CONCLUSION: In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Bases de Datos Factuales , Embolia/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Accidente Cerebrovascular/prevención & control , Centros Médicos Académicos , Anciano , Aspirina/uso terapéutico , Seguridad Computacional , Femenino , Humanos , Difusión de la Información , Masculino , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Metaanálisis en Red , Warfarina/uso terapéutico
12.
Europace ; 23(23 Suppl 2): ii14-ii22, 2021 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-33837753

RESUMEN

Atrial fibrillation (AF) remains a highly prevalent and troublesome cardiac arrhythmia, associated with substantial morbidity and mortality. Restoration and maintenance of sinus rhythm (rhythm-control therapy) is an important element of AF management in symptomatic patients. Despite significant advances and increasing importance of catheter ablation, antiarrhythmic drugs (AADs) remain a cornerstone of rhythm-control therapy. During the past 50 years, experimental and clinical research has greatly increased our understanding of AADs. As part of the special issue on paradigm shifts in AF, this review summarizes important milestones in AAD research that have shaped their current role in AF management, including (i) awareness of the proarrhythmic potential of AADs; (ii) increasing understanding of the pleiotropic effects of AADs; (iii) the development of dronedarone; and (iv) the search for AF-specific AADs. Finally, we discuss short- and long-term opportunities for better AF management through advances in AAD therapy, including personalization of AAD therapy based on individual AF mechanisms.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Antiarrítmicos/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Dronedarona , Humanos
13.
Europace ; 23(10): 1539-1547, 2021 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-34128075

RESUMEN

AIMS: Using a pre-planned post hoc analysis of patients included in X-VeRT, we evaluated predictors of sinus rhythm at 6 weeks after planned cardioversion. METHODS AND RESULTS: Receiver operating characteristic curves and logistic regression models were used to evaluate continuous and categorical variables as predictors of sinus rhythm 6 at weeks from cardioversion (end of study). The primary analysis was performed in successfully cardioverted patients with an evaluable electrocardiogram at end of study. A second analysis evaluated additional patients who spontaneously restored sinus rhythm before planned cardioversion. Of the 1504 patients with atrial fibrillation of >48 h or of unknown duration who were randomly assigned to either rivaroxaban or vitamin K antagonist, 1039 (64.6 ± 10.3 years, 73.4% male) underwent planned cardioversion and were included in this study. Patients receiving early cardioversion (i.e. between 1 and 5 days from hospitalization) had a 67% higher probability to have sinus rhythm at end of study than those who received delayed cardioversion (i.e. between 21 and 56 days from hospitalization) [odds ratio (OR) 1.67, confidence interval (CI) 1.27-2.18; P < 0.0001]. In a multivariate analysis of 17 baseline variables, patients with a CHADS2 score of 0 were 33% less likely to be in sinus rhythm than those with a CHADS2 score ≥2 (OR 0.66, CI 0.47-0.94; P = 0.0225). In the secondary analysis, spontaneous restoration of sinus rhythm was also found to predict sinus rhythm at end of study (OR 8.62, CI 1.54-48.16; P = 0.0142). CONCLUSION: In X-VeRT, early cardioversion and high CHADS2 scores predicted sinus rhythm at 6 weeks from cardioversion.


Asunto(s)
Fibrilación Atrial , Cardioversión Eléctrica , Anciano , Anticoagulantes , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rivaroxabán , Resultado del Tratamiento
14.
Europace ; 23(1): 65-72, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33249467

RESUMEN

AIMS: This post hoc analysis of ELIMINATE-AF evaluated requirements of unfractionated heparin (UFH) and procedure-related bleeding in atrial fibrillation (AF) patients undergoing ablation with uninterrupted edoxaban or vitamin K antagonist (VKA) therapy. METHODS AND RESULTS: Patients were randomized 2:1 to once-daily edoxaban 60 mg (or dose-reduced 30 mg) or dose-adjusted VKA (target international normalized ratio: 2.0-3.0). Uninterrupted anticoagulation was mandated for 21-28 days' pre-ablation and 90 days' post-ablation. During ablation, UFH administration targeted an activated clotting time (ACT) of 300-400 s. Periprocedural bleeding was differentiated between procedure-related (bleeding at puncture side, cardiac tamponade) and unrelated events. Of 614 randomized patients, 553 received study drug and underwent catheter ablation (edoxaban n = 375; VKA n = 178). The median (Q1-Q3) time from last dose to ablation procedure was 14.8 (13.3-16.5) vs. 16.5 (14.8-19.5) h (edoxaban vs. VKA group, respectively). Mean ACT (SD) ≥300 s was observed in 52% edoxaban- vs. 76% VKA-treated patients, despite a higher mean (SD) UFH dose in the edoxaban vs. VKA group [14 261 (6397) IU vs. 11 473 (4300) IU; exploratory P-value < 0.0001]. In the edoxaban group, 13 patients (3.5%) had procedure-related bleeds of whom 9 had received an UFH dose above the median (13 000 IU). In the VKA arm, 7 patients (3.9%) had procedure-related bleeds of whom 3 had received an UFH dose above the median (10 225 IU). CONCLUSION: The rate of procedure-related major/clinically relevant non-major bleeding did not differ between the treatment arms despite higher doses of UFH used with edoxaban vs. VKA to achieve a target ACT during AF ablation.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Administración Oral , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Heparina/efectos adversos , Humanos , Piridinas , Tiazoles , Resultado del Tratamiento , Vitamina K
15.
Europace ; 23(3): 329-344, 2021 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-33555020

RESUMEN

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , Consenso , Humanos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
16.
Eur Heart J ; 41(30): 2848-2859, 2020 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-32385506

RESUMEN

AIMS: A J-shaped association of cardiovascular events to achieved systolic (SBP) and diastolic (DBP) blood pressure was shown in high-risk patients. This association on oral anticoagulation is unknown. This analysis from RELY assessed the risks of death, stroke or systemic emboli, and bleeding according to mean achieved SBP and DBP in atrial fibrillation on oral anticoagulation. METHODS AND RESULTS: RE-LY patients were followed for 2 years and recruited between 22 December 2005 until 15 December 2007. 18.113 patients were randomized in 951 centres in 54 countries and 18,107 patients with complete blood pressure (BP) data were analysed with a median follow-up of 2.0 years and a complete follow-up in 99.9%. The association between achieved mean SBP and DBP on all-cause death, stroke and systemic embolic events (SSE), major, and any bleeding were explored. On treatment, SBP >140 mmHg and <120 mmHg was associated with all-cause death compared with SBP 120-130 mmHg (reference). For SSE, risk was unchanged at SBP <110 mmHg but increased at 140-160 mmHg (adjusted hazard ratio (HR) 1.81; 1.40-2.33) and SBP ≥160 mmHg (HR 3.35; 2.09-5.36). Major bleeding events were also increased at <110 mmHg and at 110 to <120 mmHg. Interestingly, there was no increased risk of major bleeding at SBP >130 mmHg. Similar patterns were observed for DBP with an increased risk at <70 mmHg (HR 1.55; 1.35-1.78) and >90 mmHg (HR 1.88; 1.43-2.46) for all-cause death compared to 70 to <80 mmHg (reference). Risk for any bleeding was increased at low DBP <70 mmHg (HR 1.46; 1.37-1.56) at DBP 80 to <90 mmHg (HR 1.13; 1.06-1.31) without increased risk at higher achieved DBP. Dabigatran 150 mg twice daily showed an advantage in all patients for all-cause death and SSE and there was an advantage for 110 mg dabigatran twice daily for major bleeding and any bleeding irrespective of SBP or DBP achieved. Similar results were obtained for baseline BP, time-updated BP, and BP as time-varying covariate. CONCLUSION: Low achieved SBP associates with increased risk of death, SSE, and bleeding in patients with atrial fibrillation on oral anticoagulation. Major bleeding events did not occur at higher BP. Low BP might identify high-risk patients not only for death but also for high bleeding risks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov-Identifier: NCT00262600.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Presión Sanguínea , Dabigatrán/efectos adversos , Humanos , Factores de Riesgo , Accidente Cerebrovascular/prevención & control , Trombina/farmacología , Warfarina/efectos adversos
17.
Circulation ; 139(20): 2292-2300, 2019 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-30773022

RESUMEN

BACKGROUND: Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (>120 kg) or low (≤60 kg) body weight because of a lack of data in these populations. METHODS: In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (≤60, >60-120, >120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding. RESULTS: Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (≤60 kg), 15 172 (83.6%) were in the midrange weight group (>60-120 kg), and 982 (5.4%) were in the high-weight group (>120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value>0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (≤60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (>60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value=0.016). CONCLUSIONS: Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low- (≤60 kg) and high-weight patients (>120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low- and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Peso Corporal , Fibrinolíticos/uso terapéutico , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Accidente Cerebrovascular/prevención & control , Tromboembolia/prevención & control , Warfarina/uso terapéutico , Anciano , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Etnicidad , Femenino , Fibrinolíticos/efectos adversos , Estudios de Seguimiento , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Obesidad/complicaciones , Modelos de Riesgos Proporcionales , Pirazoles/efectos adversos , Piridonas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Riesgo , Accidente Cerebrovascular/epidemiología , Delgadez/complicaciones , Tromboembolia/epidemiología , Resultado del Tratamiento , Warfarina/efectos adversos
18.
N Engl J Med ; 376(17): 1627-1636, 2017 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-28317415

RESUMEN

BACKGROUND: Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist oral anticoagulant therapy. Uninterrupted anticoagulation with a non-vitamin K antagonist oral anticoagulant, such as dabigatran, may be safer; however, controlled data are lacking. We investigated the safety of uninterrupted dabigatran versus warfarin in patients undergoing ablation of atrial fibrillation. METHODS: In this randomized, open-label, multicenter, controlled trial with blinded adjudicated end-point assessments, we randomly assigned patients scheduled for catheter ablation of paroxysmal or persistent atrial fibrillation to receive either dabigatran (150 mg twice daily) or warfarin (target international normalized ratio, 2.0 to 3.0). Ablation was performed after 4 to 8 weeks of uninterrupted anticoagulation, which was continued during and for 8 weeks after ablation. The primary end point was the incidence of major bleeding events during and up to 8 weeks after ablation; secondary end points included thromboembolic and other bleeding events. RESULTS: The trial enrolled 704 patients across 104 sites; 635 patients underwent ablation. Baseline characteristics were balanced between treatment groups. The incidence of major bleeding events during and up to 8 weeks after ablation was lower with dabigatran than with warfarin (5 patients [1.6%] vs. 22 patients [6.9%]; absolute risk difference, -5.3 percentage points; 95% confidence interval, -8.4 to -2.2; P<0.001). Dabigatran was associated with fewer periprocedural pericardial tamponades and groin hematomas than warfarin. The two treatment groups had a similar incidence of minor bleeding events. One thromboembolic event occurred in the warfarin group. CONCLUSIONS: In patients undergoing ablation for atrial fibrillation, anticoagulation with uninterrupted dabigatran was associated with fewer bleeding complications than uninterrupted warfarin. (Funded by Boehringer Ingelheim; RE-CIRCUIT ClinicalTrials.gov number, NCT02348723 .).


Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/cirugía , Ablación por Catéter , Dabigatrán/administración & dosificación , Hemorragia/inducido químicamente , Warfarina/administración & dosificación , Anciano , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/efectos adversos , Femenino , Hemorragia/epidemiología , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/epidemiología , Accidente Cerebrovascular/prevención & control , Warfarina/efectos adversos
19.
N Engl J Med ; 377(16): 1513-1524, 2017 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-28844193

RESUMEN

BACKGROUND: Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding. METHODS: In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization. RESULTS: The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups. CONCLUSIONS: Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y12 inhibitor than among those who received triple therapy with warfarin, a P2Y12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/uso terapéutico , Hemorragia/inducido químicamente , Intervención Coronaria Percutánea , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Adenosina/efectos adversos , Adenosina/análogos & derivados , Adenosina/uso terapéutico , Anciano , Anticoagulantes/efectos adversos , Aspirina/uso terapéutico , Fibrilación Atrial/terapia , Clopidogrel , Dabigatrán/efectos adversos , Quimioterapia Combinada/efectos adversos , Femenino , Hemorragia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Riesgo , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Warfarina/efectos adversos , Warfarina/uso terapéutico
20.
Eur Heart J ; 40(19): 1553-1562, 2019 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-30793734

RESUMEN

AIMS: After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment. METHODS AND RESULTS: In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35-0.63) for 110 mg and 0.67 (0.50-0.90) for 150 mg]; elective PCI [0.57 (0.43-0.76) for 110 mg and 0.76 (0.56-1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28-0.76) for 110 mg and 0.59 (0.34-1.04) for 150 mg]; or clopidogrel [0.51 (0.41-0.64) for 110 mg and 0.73 (0.58-0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10. CONCLUSION: The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.


Asunto(s)
Síndrome Coronario Agudo/terapia , Antitrombinas/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Dabigatrán/uso terapéutico , Hemorragia/inducido químicamente , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/complicaciones , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Fibrilación Atrial/complicaciones , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/complicaciones , Quimioterapia Combinada , Terapia Antiplaquetaria Doble , Procedimientos Quirúrgicos Electivos , Femenino , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Warfarina/uso terapéutico
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