BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

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Obesity is a highly prevalent condition associated with several diseases. Physical exercise has been considered as a non-pharmacological tool in the treatment of obesity. However, several aspects underlying exercise evaluation and prescription in obesity and associated pathologies are still under investigation. Although many research involving exercise have been performed in animal models, there is a lack of protocols for aerobic capacity assessment in obese animals, such as the ob/ob mice. This study aimed the following: (i) to verify the possibility of determining the lactate threshold (LT) on swimming exercise in ob/ob mice and in non-obese heterozygote mice (ob/OB), through visual inspection (vLT) and polynomial adjustment (pLT); and (ii) to verify if the LT determined through these protocols corresponds to the maximal lactate steady state (MLSS). Eight ob/ob and ten ob/OB mice performed an incremental exercise test to determine vLT and pLT as well as constant-load exercise bouts to determine MLSS. There were no within-group differences between vLT, pLT and MLSS [ob/ob: ~5.3% body weight (BW); ob/OB: ~3·6%BW] with a high agreement among protocols. In conclusion, the identification of the LT and MLSS intensities was possible for both groups. These data suggest that the proposed protocols may be used in new research on the effects of different exercise intensities on some aspects of obesity.

Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

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RESUMOIntrodução: A crescente procura da natação como um tratamento não-farmacológico da hipertensão arterial tem aumentado. Objetivo: Analisar as respostas da pressão arterial (PA) após o exercício de natação e durante a rotina diária de trabalho de indivíduos pré-hipertensos. Métodos: Oito indivíduos pré-hipertensos (128,2 ± 7,8 / 77,8 ± 6,0mmHg; 41,8 ± 3,2 anos; 84,7 ± 17,9kg; 180,4 ± 4,8cm; 27,3 ± 5,8kg.m 2(-1) ) foram submetidos a duas sessões, sendo uma de natação (SN) e a outra de controle (SC). A PA foi medida no repouso pré-exercício e durante 12 horas de recuperação pós-exercício. Na SN, os pacientes nadaram por 45min em uma intensidade moderada a alta (PSE 14,5 ± 1,6), e, durante a SC, os sujeitos permaneceram em repouso na posição sentada pelo mesmo período de tempo. Resultados: ANOVA para medidas repetidas evidenciou diminuição significativa (p ≤ 0,05) na PAS por duas horas após a SN em relação ao repouso, e uma diferença significativa entre os deltas do PAS (Δ -PAS variação na recuperação pós-exercício em relação ao repouso pré-exercício) foi observada entre as sessões na primeira e segunda horas após a recuperação, respectivamente (ΔSS = -10,4 e -9,3 vs. ΔCS = 0,8 e 4,4mmHg, p < 0,05). Não houve diferenças significativas da PAD, intra e entre as sessões. Conclusão: O exercício de natação em intensidade moderada a alta foi eficaz para promover redução da PA pós-exercício em indivíduos hipertensos durante a sua rotina de trabalho.Palavras-chave: hipotensão pós-exercício, pressão arterial, frequência cardíaca, percepção subjetiva de esforço. ABSTRACTIntroduction: The increasing demand for swimming as a non-pharmacological treatment of hypertension has increased. PURPOSE: To analyze the blood pressure (BP) responses after swimming and during the daily work routine of pre-hypertensive individuals. Methods: Eight male borderline hypertensive individuals (128.2 ± 7.8 / 77.8 ± 6.0 mmHg; 41.8 ± 3.2 years; 84.7 ± 17.9 kg; 180.4 ± 4.8 cm; 27.3 ± 5.8 kg.m2 (-1)) were submitted to a swimming exercise (SS) and control (CS) sessions. BP was measured at pre-exercise rest and during 12 hours of the post-exercise recovery. In SS, patients swan for 45 minutes in a moderate-high intensity (PSE 14.5 ± 1.6), and during CS the subjects remained at seated rest for 45 min. Results: ANOVA for repeated measures evidenced significant decrease (P ≤ 0.05) in SBP in the for 2 hours after SS in comparison to rest, and a significant difference between the SBP deltas (Δ -SBP variation in the post-exercise recovery compared to pre-exercise rest) was observed when comparing sessions at 1 and 2 hours after recovery, respectively (ΔSS = -10.4 and -9.3 vs. ΔCS = 0.8 and 4.4 mmHg, p <0.05). There were not significant differences in DBP within and between sessions. Conclusion: Swimming exercise at moderate-high intensity was effective in promoting post-exercise BP reduction for borderline hypertensive individuals during their daily work routine.

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