Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 354
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-31687762

RESUMO

INTRODUCTION: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. METHODS: In a post-hoc analysis of the ENGAGE AF-TIMI 48 trial, we analyzed 21,105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen (LDER), or warfarin. We used the Updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI=0, 1, 2, 3 and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. RESULTS: There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI=0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI=0, 1, 2, 3 or ≥ 4 were 5.9%, 8.7%, 6.6%, 10.3% and 13.6% (Ptrend <0.001). There were no significant interactions between treatment with HDER vs warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction >0.10 for each). CONCLUSIONS: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs warfarin were independent of the degree of comorbidity present.

2.
3.
Eur J Heart Fail ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31777160

RESUMO

AIMS: The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular (CV) death or heart failure (HF) hospitalization in a population with atrial fibrillation (AF). METHODS AND RESULTS: In a prospective echocardiographic substudy of the Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study, 971 patients underwent transthoracic echocardiography. The associations between LA structure (LA volume index [LAVi]) and function (LA emptying fraction [LAEF] and LA expansion index [LAEi]) and risk for the composite endpoint of CV death or HF hospitalization, and its components, were assessed. Over a median follow-up of 2.5 years, 142 patients (14.6%) experienced CV death or HF hospitalization. Higher LAVi and lower LAEF and LAEi were each associated with a higher unadjusted risk for the composite outcome and its components. After adjustment for clinical and echocardiographic confounders, only measures of impaired LA function were predictive of the composite outcome (hazard ratio [HR] per 1 standard deviation [SD] decrease in LAEF: 1.35; 95% confidence interval [CI] 1.09-1.67 [P = 0.005]; HR per 1 SD decrease in LAEi: 1.34; 95% CI 1.06-1.69 [P = 0.012]). These findings were similar regardless of left ventricular ejection fraction, history of HF or whether patients were in AF or sinus rhythm at the time of the echocardiographic examination. CONCLUSIONS: In patients with AF, LA dysfunction was significantly associated with an increased risk for CV death or HF hospitalization and was more predictive of these outcomes than LA size. These parameters may help to identify AF patients at greatest risk for the development of HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00781391.

4.
Circulation ; 140(22): 1792-1801, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31597460

RESUMO

BACKGROUND: Numerous scales exist for the classification of major bleeding events. Limited data compare the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation. Here, we analyze bleeding outcomes according to the ISTH (International Society on Thrombosis and Hemostasis), TIMI (Thrombolysis in Myocardial Infarction), GUSTO (Global Usage of Strategies to Open Occluded Arteries), and BARC (Bleeding Academic Research Consortium) bleeding scales in the ENGAGE AF (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation)-TIMI 48 trial (NCT00781391) of edoxaban versus warfarin. METHODS: A total of 21 105 patients with atrial fibrillation at risk for stroke (CHADS2 score ≥2) were enrolled in the ENGAGE AF-TIMI 48 trial comparing warfarin with a higher- (60/30 mg daily) or lower- (30/15 mg daily) dose edoxaban regimen. Median follow-up was 2.8 years. Bleeding events occurring among on-treatment patients were examined. Annualized event rates were calculated by the ISTH, TIMI, GUSTO, and BARC scales and compared across treatment arms. Cox proportional hazards for a first bleeding event of each type were calculated for higher-dose edoxaban regimen vs warfarin and lower-dose edoxaban regimen versus warfarin. RESULTS: A total of 10 311 bleeding events were reported. In a comparison of the most severe events in each scale, ISTH major bleeding was the most common (n=1289), followed by TIMI major (n=548), GUSTO severe/life-threatening (n=347), and BARC 3c+5 (n=276) bleeding. Lower bleeding risk with edoxaban compared with warfarin was seen regardless of bleeding scale (higher-dose edoxaban regimen range: hazard ratio [HR], 0.47 [95% CI, 0.35-0.62] for BARC 3c+5 versus HR, 0.80 [95% CI, 0.71-0.91] for ISTH major; lower-dose edoxaban regimen range: HR, 0.32 [95% CI, 0.23-0.45] for BARC 3c+5 versus HR, 0.47 [95% CI, 0.41-0.55] for ISTH major). Furthermore, a gradient of more pronounced risk reduction with edoxaban was observed with greater severity of first bleeding event (higher-dose edoxaban regimen: HR, 0.47 [95% CI, 0.35-0.62] for BARC 3c+5 bleeds versus HR, 0.86 [95% CI, 0.81-0.91] for any BARC bleed; lower-dose edoxaban regimen: HR, 0.32 [95% CI, 0.23-0.45] for BARC 3c+5 bleeds versus HR, 0.68 [95% CI, 0.63-0.72] for any BARC bleed). The direction of this trend was consistent for both gastrointestinal bleeding and nongastrointestinal bleeding. CONCLUSIONS: Among patients with atrial fibrillation at risk for stroke, there was a >4-fold difference in the frequency of the most severe bleeding events across commonly used bleeding scales. Furthermore, the relative safety of edoxaban compared with warfarin tended to increase with greater severity of bleeding. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00781391.

5.
PLoS One ; 14(9): e0222061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532795

RESUMO

BACKGROUND: The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes. METHODS AND RESULTS: We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p<0.0001; vs. AG: 1.76±0.35, p = 0.03). When randomized to 6-months of O-3FA treatment, GG patients demonstrated significant lowering of LV end-systolic volume index (LVESVi), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and galectin-3 levels compared to placebo (-4.4 vs. 1.2 ml/m2, -733 vs. -181 pg/mL, and -2.0 vs. 0.5 ng/mL; p = 0.006, 0.006, and 0.03, respectively). In contrast, patients with either AA or AG genotype did not demonstrate significant lowering of LVESVi, NT-proBNP, or galectin-3 levels from O-3FA treatment, compared to placebo. The odds ratios for improving LVESVi by 10% with O-3FA treatment was 7.2, 1.6, and 1.2 in patients with GG, AG, and AA genotypes, respectively. CONCLUSION: Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov Identifier: NCT00729430.

6.
J Am Coll Cardiol ; 74(2): 179-189, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31296289

RESUMO

BACKGROUND: Patients with liver disease have increased risk of thrombosis and bleeding but are typically excluded from trials of direct oral anticoagulant agents. OBJECTIVES: This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), clinical efficacy and safety of edoxaban versus warfarin in patients with atrial fibrillation (AF) and history of liver disease. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction Study 48) was a randomized, double-blind trial comparing edoxaban with warfarin in patients with AF followed for 2.8 years. History of liver disease was defined as investigator-reported liver disease or >2-fold transaminase elevation at randomization. The primary efficacy and safety endpoints of stroke or systemic embolic event (SSEE) and major bleeding were assessed stratified by history of liver disease. PK/PD assessments of edoxaban included endogenous and extrinsic factor Xa activity and edoxaban concentration. RESULTS: Among 21,105 patients, 1,083 (5.1%) had a history of liver disease; they had a higher prevalence of many comorbidities. The adjusted risks of SSEE were similar (adjusted hazard ratio [HRadj]: 0.90; 95% confidence interval [CI]: 0.67 to 1.22; p = 0.50), but major bleeding was more common in patients with liver disease (HRadj: 1.38; 95% CI: 1.10 to 1.74; p = 0.005). There were no significant differences in PK/PD assessment of edoxaban in patients with versus without liver disease. The HRs for higher-dose edoxaban versus warfarin for SSEE were 0.86 (95% CI: 0.73 to 1.01) in patients without and 1.11 (95% CI: 0.54 to 2.30) with liver disease (p for interaction [pint] = 0.47), major bleeding 0.80 (95% CI: 0.70 to 0.91) in patients without and 0.91 (95% CI: 0.56 to 1.47) with liver disease (pint = 0.63). There were no significant differences in hepatic adverse events between the 2 treatment groups. CONCLUSIONS: Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease. A history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin. Hepatic adverse events were similar between edoxaban and warfarin.

7.
Hypertension ; 74(3): 597-605, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31352829

RESUMO

Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), 19,679 patients with atrial fibrillation and hypertension were categorized according to average systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary efficacy and safety end points were the time to the first stroke or systemic embolic event and the time to the first International Society of Thrombosis and Hemostasis major bleeding event, respectively. Risk was calculated using Cox proportional hazards models based on average SBP and DBP and adjusting for 18 clinical characteristics. The efficacy and safety of a higher dose edoxaban regimen (60/30 mg) versus warfarin were evaluated with stratification by average SBP and DBP. Stroke/systemic embolic event occurred significantly more frequently in patients with elevated average SBP (hazard ratio, 2.01; 95% CI, 1.50-2.70 for SBP ≥150 mm Hg relative to 130-139 mm Hg) or DBP (hazard ratio, 2.36; 95% CI, 1.76-3.16 for DBP ≥90 mm Hg relative to 75-<85 mm Hg). The higher dose edoxaban regimen reduced stroke/systemic embolic event across the full range of SBP (Pinteraction=0.55) and DBP (Pinteraction=0.44) compared with warfarin. The higher dose edoxaban regimen reduced the risk of major bleeding events, including intracranial hemorrhage, without modification by average SBP (Pinteraction=0.29). The relative safety of edoxaban was most pronounced in patients with elevated DBP (Pinteraction=0.007). The efficacy and safety of edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Comorbidade , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Hipertensão/diagnóstico , Modelos Logísticos , Masculino , Segurança do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Análise de Sobrevida , Resultado do Tratamento
8.
Eur Heart J ; 40(19): 1541-1550, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30624719

RESUMO

AIMS: To investigate the relationship between body mass index (BMI) and outcomes in patients with atrial fibrillation (AF). METHODS AND RESULTS: In the ENGAGE AF-TIMI 48 trial, patients with AF were randomized to warfarin (international normalized ratio 2.0-3.0) or edoxaban. The cohort (N = 21 028) included patients across BMI categories (kg/m2): underweight (<18.5) in 0.8%, normal (18.5 to <25) in 21.4%, overweight (25 to <30) in 37.6%, moderately obese (30 to <35) in 24.8%, severely obese (35 to <40) in 10.0%, and very severely obese (≥40) in 5.5%. In an adjusted analysis, higher BMI (continuous, per 5 kg/m2 increase) was significantly and independently associated with lower risks of stroke/systemic embolic event (SEE) [hazard ratio (HR) 0.88, P = 0.0001], ischaemic stroke/SEE (HR 0.87, P < 0.0001), and death (HR 0.91, P < 0.0001), but with increased risks of major (HR 1.06, P = 0.025) and major or clinically relevant non-major bleeding (HR 1.05, P = 0.0007). There was a significant interaction between sex and increasing BMI category, with lower risk of ischaemic stroke/SEE in males and increased risk of bleeding in women. Trough edoxaban concentration and anti-Factor Xa activity were similar across BMI groups >18.5 kg/m2, while time in therapeutic range for warfarin improved significantly as BMI increased (P < 0.0001). The effects of edoxaban vs. warfarin on stroke/SEE, major bleeding, and net clinical outcome were similar across BMI groups. CONCLUSION: An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding. The efficacy and safety profiles of edoxaban were similar across BMI categories ranging from 18.5 to >40.

9.
J Am Heart Assoc ; 8(1): e008096, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30596310

RESUMO

Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre- and in-hospital care and outcomes from 2008 to 2012 for patients with ST -segment-elevation myocardial infarction at US hospitals, using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines Registry. In-hospital adjusted mortality was calculated including and excluding cardiac arrest as a reason for primary percutaneous coronary intervention delay. A total of 147 466 patients from 485 hospitals were analyzed. There was a decrease in the proportion of eligible patients not treated with reperfusion (6.2% versus 3.3%) and treated with fibrinolytic therapy (13.4% versus 7.0%). Median time from symptom onset to first medical contact was unchanged (≈50 minutes). Use of prehospital ECGs increased (45% versus 71%). All major reperfusion times improved: median first medical contact-to-device for emergency medical systems transport to percutaneous coronary intervention-capable hospitals (93 to 84 minutes), first door-to-device for transfers for primary percutaneous coronary intervention (130 to 112 minutes), and door-in-door-out at non-percutaneous coronary intervention-capable hospitals (76 to 62 minutes) (all P<0.001 over 5 years). Rates of cardiogenic shock and cardiac arrest, and overall in-hospital mortality increased (5.7% to 6.3%). Adjusted mortality excluding patients with known cardiac arrest decreased by 14% at 3 years and 25% at 5 years ( P<0.001). Conclusions Quality of care for patients with ST -segment-elevation myocardial infarction improved over time in Mission: Lifeline, including increased use of reperfusion therapy and faster times-to-treatment. In-hospital mortality improved for patients without cardiac arrest but did not appear to improve overall as the number of these high-risk patients increased.

10.
Eur Heart J ; 40(19): 1518-1527, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30590425

RESUMO

AIMS: Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races. METHODS AND RESULTS: There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively). CONCLUSION: Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.

11.
Circulation ; 139(6): 760-771, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586727

RESUMO

BACKGROUND: The ABC (age, biomarker, clinical history)-stroke and ABC-bleeding risk scores incorporate clinical variables and cardiovascular biomarkers to estimate risk of stroke or systemic embolic events and bleeding, respectively, in patients with atrial fibrillation. These scores have been proposed for routine clinical use, but their performance in external cohorts remains uncertain. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 8705 patients, analyzing baseline high-sensitivity troponin T (hsTnT), NT-proBNP (N-terminal B-type natriuretic peptide), and growth differentiation factor-15 (GDF-15), as well as in serial samples after 12 months. The ABC-stroke (age, prior stroke/transient ischemic attack, hsTnT, NT-proBNP) and ABC-bleeding (age, prior bleeding, hemoglobin, hsTnT, and GDF-15) scores were tested. Hazard ratios were adjusted for estimated glomerular filtration rate and the components of the CHA2DS2-VASc and HAS-BLED scores, respectively. Discrimination and reclassification were compared with these established scores. RESULTS: Median baseline hsTnT, NT-proBNP, and GDF-15 levels were 13.7 ng/L (25th-75th percentiles, 9.6-20.4 ng/L), 811 pg/mL (386-1436 pg/mL), and 1661 pg/mL (1179-2427 pg/mL), respectively. Elevated hsTnT, NT-proBNP, and GDF-15 were independently associated with higher rates of stroke or systemic embolic events, and elevated hsTnT and GDF-15 were independently associated with higher rates of major bleeding ( P<0.001 for each). The ABC-stroke and ABC-bleeding scores were well calibrated and yielded higher c indexes than the CHA2DS2-VASc score for stroke or systemic embolic events (0.67 [95% CI, 0.65-0.70] versus 0.59 [95% CI, 0.57-0.62]; P<0.001) and HAS-BLED score for major bleeding (0.69 [95% CI, 0.66-0.71] versus 0.62 [95% CI, 0.60-0.64]; P<0.001), respectively. The ABC-stroke and ABC-bleeding scores stratified patients within CHA2DS2-VASc and HAS-BLED risk categories ( P<0.001 for both). Patients with ABC-bleeding scores predicting a high 1-year risk of bleeding (>2%) derived greater benefit from treatment with edoxaban compared with warfarin. CONCLUSIONS: The ABC-stroke and ABC-bleeding scores evaluated in this anticoagulated clinical trial cohort were well calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively. These scores may help identify patients most likely to derive a benefit from treatment with non-vitamin K antagonist oral anticoagulants. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00781391.

12.
Europace ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30462220

RESUMO

Aims: Pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy device implantations and generator changes are frequently performed in patients receiving direct oral anticoagulants. In an exploratory analysis, we investigated the outcome of patients undergoing such device procedures in the ENGAGE AF-TIMI 48 trial. Methods and results: During the trial, 1217 device procedures were performed in 1145 patients, with intervention dates available for 1203 procedures. Two hundred and twenty-five procedures (in 212 patients) were performed >30 days after study drug was stopped and are not included in the event analysis. For most interventions (n = 728, 74%), study drug was interrupted >3 days (median for the entire cohort: 5 days, interquartile range 0-11 days); 250 interventions were performed with ≤3 days study drug interruption. During the first 30 days after the procedure, six strokes/systemic embolic events (SEEs) (three each in the lower-dose edoxaban and warfarin arm) and one major bleeding event (in the lower-dose edoxaban arm) occurred; no stroke/SEEs or major bleeds occurred around the 295 device procedures in the higher-dose edoxaban arm. Two ischaemic and one major bleeding event occurred after the 288 device procedures performed with ≤3 days periprocedural interruption of study drug. Conclusion: In this first experience of patients undergoing device surgery with edoxaban, a low risk of ischaemic and bleeding events was observed during the first 30 days post-procedure. Our data are in line with current recommendations of no or only brief interruption of non-vitamin K antagonist oral anticoagulants prior to cardiac device surgery.

13.
J Am Heart Assoc ; 7(16): e008987, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30369307

RESUMO

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF - TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230-771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78-3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07-2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83-1.42). Relative outcomes with higher-dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31-1.15] for malignancy versus HR , 0.89 [95% CI, 0.76-1.05] for no malignancy; interaction P=0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69-1.40] for malignancy versus HR , 0.79 [95% CI, 0.69-1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher-dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31-0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88-1.18; interaction P=0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.

15.
Eur Heart J Acute Cardiovasc Care ; : 2048872618796990, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30318902

RESUMO

BACKGROUND: Patients with atrial fibrillation and concomitant coronary artery disease (CAD) are at higher risk for myocardial infarction or cardiovascular death, often require antiplatelet therapy and are therefore exposed to an increased risk of bleeding. This meta-analysis aimed to compare the efficacy and safety profile of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin in patients with atrial fibrillation and concomitant CAD. MATERIALS AND METHODS: We performed a trial-level meta-analysis of CAD subgroups from four trials of NOAC versus warfarin in patients with atrial fibrillation, comparing the primary trial endpoints (efficacy: stroke or systemic embolic event; safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus those without CAD, and used interaction testing to assess for treatment effect modification. RESULTS: In total, 58,606 patients with established CAD were included in this meta-analysis. NOACs reduced the risk of stroke/systemic embolic event irrespective of presence of CAD (CAD: 0.76 (0.56-1.04); no CAD: hazard ratio 0.77 (0.56-1.06); p-INT 0.93). Similarly, there was no effect modification by presence of CAD for major bleeding (CAD: hazard ratio 0.92 (0.65-1.32), no CAD: 0.83 (0.61-1.12); p-INT 0.46) or myocardial infarction (CAD: hazard ratio 0.95 (0.62-1.44); no CAD: hazard ratio 0.95 (0.60-1.50); p-INT = 0.98). While NOACs reduced all-cause mortality in patients without CAD compared with warfarin (hazard ratio 0.85 (0.71-1.02)), there was no difference in mortality between NOACs and warfarin in the CAD group (hazard ratio 0.99 (0.82-1.20); p-INT 0.01). CONCLUSION: The present meta-analysis of four trials supports that NOACs are safe and at least as effective as warfarin in patients with atrial fibrillation and established CAD.

16.
J Am Coll Cardiol ; 72(13): 1466-1475, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30236308

RESUMO

BACKGROUND: There is limited information about the use of antithrombotic therapies and outcomes of Latin American (LatAm) subjects with atrial fibrillation. The global ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial compared the efficacy and safety of edoxaban versus warfarin over a median follow-up of 2.8 years. OBJECTIVES: The authors aimed to compare adjusted outcomes in Latin America versus outside Latin America and to compare outcomes stratified by anticoagulant treatment and region. METHODS: The authors analyzed clinical characteristics and outcomes, adjusted for baseline characteristics, the Human Development Index, and randomized treatment of 2,661 LatAm versus 18,444 non-Latin American subjects (nLAS). RESULTS: When compared with nLAS, LatAm subjects had a similar overall risk for stroke. After multivariate adjustment, the risks of stroke/systemic embolism (hazard ratio [HR]: 1.19; 95% confidence interval (CI): 0.96 to 1.47; p = 0.11) and major bleeding (HR: 1.10; 95% CI: 0.89 to 1.36; p = 0.39) were similar in LatAm and nLAS. LatAm subjects were at higher adjusted risk of death (HR: 1.48; 95% CI: 1.30 to 1.69; p < 0.001) and intracranial hemorrhage (ICH) (HR: 1.55; 95% CI: 1.00 to 2.41; p = 0.049). In both regions, when compared with warfarin, edoxaban reduced stroke/systemic embolism (HR: 0.64 and 0.91 in LatAm and nLAS, respectively), major bleeding (HR: 0.71 and 0.82), and cardiovascular death (HR: 0.78 and 0.88), without evidence of regional heterogeneity (pint = 0.41, 0.50, and 0.70, respectively). There was a greater reduction in hemorrhagic stroke with edoxaban in LatAm (HR: 0.16) than in nLAS (HR: 0.64; pint = 0.037). CONCLUSIONS: After multivariable adjustment, LatAm subjects with atrial fibrillation had higher rates of intracranial hemorrhage and death than nLAS. Outcomes with higher-dose edoxaban versus warfarin were at least as favorable in LatAm subjects as in nLAS, with an even greater reduction in hemorrhagic stroke seen in LatAm.

17.
Eur Heart J ; 39(42): 3777-3779, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30239697
18.
Eur Heart J ; 39(42): 3810-3820, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30239711

RESUMO

Aims: Although presenting features and early sequelae of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are well described, less is known about longer-term risks and modes of death. The purpose of this study was to characterize modes of death following NSTE-ACS in clinical trial populations. Methods and results: We evaluated 66 252 patients with NSTE-ACS enrolled in 14 Thrombolysis in Myocardial Infarction (TIMI) trials, examining baseline characteristics and modes and timing of death. Of the 66 252 patients followed for a median of 372 (interquartile range 218-521) days, 3147 (4.8%) died by the time of last follow-up. Of the 2606 patients (82.8%) with known modes of death, 75.1% were related to a cardiovascular (CV) event, 3.0% were related to a bleeding event (including intracranial haemorrhage), and 21.8% were related to a non-CV/non-bleeding event. The most common modes of CV death were sudden death (SD) and recurrent myocardial infarction (MI) (36.4% and 23.4%, respectively, of CV deaths). The proportion of CV deaths related to recurrent MI was higher in the first 30 days than it was after 30 days following NSTE-ACS (30.6% vs. 18.7%), whereas the proportion of SD was lower in the first 30 days than after 30 days (21.6% vs. 46.2%). Conclusion: Sudden death represents the largest proportion of CV deaths after 30 days among patients enrolled in CV clinical trials with NSTE-ACS. Further investigations aimed at defining the epidemiology of SD and developing specific therapies and management approaches to reduce SD following NSTE-ACS may be critical to reducing late mortality.

20.
Eur Heart J Acute Cardiovasc Care ; : 2048872618790561, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30039978

RESUMO

BACKGROUND: The relative efficacy and safety profile of the oral Factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation and established coronary artery disease (CAD) has not been analyzed. MATERIALS AND METHODS: In the ENGAGE AF-TIMI 48 trial, two edoxaban regimens were compared with warfarin in 21,105 patients with atrial fibrillation and CHADS2 ⩾2. We analyzed the primary trial endpoints (efficacy: stroke or systemic embolic event, safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus without CAD, and used interaction testing to assess for treatment effect modification. RESULTS: The 4510 patients (21.4%) with known CAD were older, more likely male, on aspirin, with lower creatinine clearance and higher CHADS2 and HAS-BLED scores ( p <0.001 for each). Treatment with the higher-dose edoxaban regimen (versus warfarin) in patients with known CAD tended to have a greater reduction in stroke/systemic embolic event compared with patients without CAD (CAD: hazard ratio 0.65 (0.46-0.92) versus no CAD: hazard ratio 0.94 (0.79-1.12), p-INT 0.062) and also in myocardial infarction (CAD: hazard ratio 0.69 (0.49-0.98) versus no CAD: hazard ratio 1.24 (0.89-1.72), p-INT 0.017), while there was a similar reduction in bleeding irrespective of CAD status (hazard ratio 0.81 and 0.80, p-INT 0.97). Presence or absence of CAD did not modify the efficacy or safety profile of the lower-dose edoxaban regimen (versus warfarin). CONCLUSION: The reduction in ischemic events with the higher-dose edoxaban regimen versus warfarin was greater in patients with CAD, while bleeding was significantly reduced with edoxaban regardless of CAD status. The efficacy and safety profile of the lower-dose edoxaban regimen relative to warfarin was unaffected by CAD status.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA