Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload.

BACKGROUND: In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. OBJECTIVES: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. METHODS: In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m2; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach. RESULTS: We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (-2.4 ± 2.1 kg vs. -0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. CONCLUSIONS: Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557).

Group exercise, education, and combination self-management in women with fibromyalgia: a randomized trial.

BACKGROUND: Self-management has increasingly been recommended as part of standard care for fibromyalgia, a common, poorly understood condition with limited treatment options. Data that assess popular self-management recommendations are scarce. We evaluated and compared the effectiveness of 4 common self-management treatments on function, symptoms, and self-efficacy in women with fibromyalgia. METHODS: A total of 207 women with confirmed fibromyalgia were recruited from September 16, 2002, through November 30, 2004, and randomly assigned to 16 weeks of (1) aerobic and flexibility exercise (AE); (2) strength training, aerobic, and flexibility exercise (ST); (3) the Fibromyalgia Self-Help Course (FSHC); or (4) a combination of ST and FSHC (ST-FSHC). The primary outcome was change in physical function from baseline to completion of the intervention. Secondary outcomes included social and emotional function, symptoms, and self-efficacy. RESULTS: Improvements in the mean Fibromyalgia Impact Questionnaire score in the 4 groups were -12.7 for the ST-FSHC group, -8.2 for the AE group, -6.6 for the ST group, and -0.3 for the FSHC group. The ST-FSHC group demonstrated greater improvement than the FSHC group (mean difference, -12.4; 95% confidence interval [CI], -23.1 to -1.7). The ST-FSHC (mean difference, 13.6; 95% CI, 2.3 to 24.9) and AE (mean difference, 13.1; 95% CI, 1.6 to 25.6) groups had similar improvements in physical function scores on the 36-Item Short-Form Health Survey. Bodily pain scores on the 36-Item Short-Form Health Survey improved in the ST-FSHC (14.8), AE (13.2), and ST (5.7) groups. Social function, mental health, fatigue, depression, and self-efficacy also improved. The beneficial effect on physical function of exercise alone and in combination with education persisted at 6 months. CONCLUSIONS: Progressive walking, simple strength training movements, and stretching activities improve functional status, key symptoms, and self-efficacy in women with fibromyalgia actively being treated with medication. The benefits of exercise are enhanced when combined with targeted self-management education. Our findings suggest that appropriate exercise and patient education be included in the treatment of fibromyalgia.