Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Efficacy and Safety of Tadalafil Once Daily in the Treatment of Men With Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Results of an International Randomized, Double-Blind, Placebo-Controlled Trial

Background: Tadalafil is being investigated for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH-LUTS). Objective: To assess efficacy, including onset, and safety of tadalafil on BPH-LUTS and the subject's and clinician's perception of changes in urinary symptoms. Design, setting, and participants: This randomized, double-blind, placebo-controlled, 12-week trial enrolled men >= 45 yr of age with BPH-LUTS for >6 mo, International Prostate Symptom Score (IPSS) >= 13, and maximum urine flow rate (Q(max)) >= 4 to <= 15 ml/s. Intervention: Tadalafil 5 mg (n = 161) or placebo (n = 164), once daily. Measurements: Analysis of covariance (ANCOVA) modeling evaluated change from baseline in continuous efficacy variables. Categoric efficacy variables were analyzed with the Cochran-Mantel-Haenszel test, and between-group differences in treatment-emergent adverse events (TEAEs) were assessed using the Fisher exact test. Results and limitation: Tadalafil significantly improved IPSS results, from baseline to endpoint, compared to placebo (-5.6 vs -3.6; p = 0.004). Reduction in IPSS results was apparent after 1 wk and significant after 4 wk (tadalafil -5.3 vs placebo -3.5; p = 0.003). The BPH Impact Index (BII) was not assessed at week 1; however, BII improvement was apparent at 4 wk (tadalafil -1.8 vs placebo -1.2; p = 0.029) and continued at 12 wk (tadalafil -1.8 vs placebo -1.3; p = 0.057). Tadalafil significantly improved the International Index of Erectile Function-Erectile Function score in sexually active men with erectile dysfunction (ED; 6.7 vs 2.0; p < 0.001) at 12 wk (not assessed at week 1). Few subjects reported one TEAE or more (p = 0.44). For tadalafil, the most common TEAEs were headache (3.7%) and back pain (3.1%). Tadalafil did not significantly improve Q(max) or reduce postvoid residual volume. Conclusions: Tadalafil 5 mg once daily for 12 wk resulted in a clinically meaningful reduction in total IPSS results as early as 1 wk and achieved statistical significance at 4 wk in men with BPH-LUTS. The adverse event profile was consistent with that previously reported in men with ED. Trial registration: This clinical trial is registered on the clinicaltrials.gov website (http://www.clinicaltrials.gov). The registration number is NCT00827242. (C) 2011 Published by Elsevier B. V. on behalf of European Association of Urology

Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction.

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Effects of Ramipril and Rosiglitazone on Cardiovascular and Renal Outcomes in People With Impaired Glucose Tolerance or Impaired Fasting Glucose : Results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial

OBJECTIVE—Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS—A total of 5,269 people aged ≥30 years, with IGT and/or IFG without known CVD or renal insufficiency, were randomized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo. A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up. RESULTS—Compared with placebo, neither ramipril (15.7% [412 of 2,623] vs. 16.0% [424 of 2,646]; hazard ratio [HR] 0.98 [95% CI 0.84–1.13]; P = 0.75) nor rosiglitazone (15.0% [394 of 2,635] vs. 16.8% [442 of 2,634]; 0.87 [0.75–1.01]; P = 0.07) reduced the risk of the cardiorenal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure (0.53 vs. 0.08%; HR 7.04 [95% CI 1.60–31.0]; P = 0.01) but reduced the risk of the renal component (0.80 [0.68–0.93]; P = 0.005); prevention of diabetes was independently associated with prevention of the renal component (P &amp;lt; 0.001). CONCLUSIONS—Ramipril did not alter the cardiorenal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure.The DREAM Trial Investigator