RESUMEN
BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).
Asunto(s)
4-Hidroxicumarinas/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Piridinas/uso terapéutico , Tiazoles/uso terapéutico , Reemplazo de la Válvula Aórtica Transcatéter , Vitamina K/antagonistas & inhibidores , 4-Hidroxicumarinas/efectos adversos , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Mortalidad , Fenindiona/análogos & derivados , Fenindiona/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Piridinas/efectos adversos , Tiazoles/efectos adversos , Tromboembolia/prevención & control , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversosRESUMEN
BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular (LV) dysfunction enrolled in the prospective Surgical Treatment for Ischemic Heart Failure Study (STICH) trial. METHODS: The STICH trial randomized 1212 patients [148 (12%) women and 1064 (88%) men] with CAD and LV ejection fraction (EF)≤ 35% to CABG + medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 vs 59.3, p=0.016) with higher BMI (27.9 vs 26.7, p=0.001). Women had more CAD risk factors (diabetes 55.4% vs 37.2%, hypertension 70.9% vs 58.6%, hyperlipidemia 70.3% vs 58.9%) except for smoking (13.5% vs 21.8%), and had lower rates of prior CABG (0% vs 3.4%, all p<0.05) than men. Moreover, women had higher New York Heart Association (NYHA) class (Class III/IV 66.2% vs 57.0%), lower 6-min walk capacity (300m vs 350m) and lower Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores (51 vs 63) (all p<0.05) than men. Moreover, women had higher New York Heart Association (NYHA) class (Class III/IV 66.2% vs 57.0%), lower 6-min walk capacity (300m vs 350m) and lower Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores (51 vs 63) (all p<0.05). Over 10-years of follow up, all- cause mortality (49.0% vs 65.8%, adjusted HR 0.67, CI 0.520.86, p=0.002) and CV mortality (34.3% vs 52.3%, adjusted HR 0.65, CI 0.480.89, p=0.006) were significantly lower in women compared to men. With randomization to CABG + MED vs. MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, CV mortality, or the composite of all-cause mortality or CV hospitalization (all p>0.05). In addition, surgical deaths were not statistically different (1.5% vs 5.1%, p=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG + MED vs. MED on all-cause mortality, CV mortality, the composite of death or CV hospitalization, or surgical deaths in patients with ischemic LV dysfunction. Thus, sex should not influence treatment decisions regarding CABG in these patients.