Blood pressure changes associated with sibutramine and weight management - an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes trial (SCOUT).

OBJECTIVE: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (<130/<85), high-normal (130 to <140/85 to <90) or hypertensive (>or=140/>or=90); weight change categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change in the class of antihypertensive medication used and who did not report an increase in antihypertensive medication use were analysed. RESULTS: At entry, approximately 50% of patients were hypertensive and 26% were high-normal. In hypertensive patients, blood pressure changes (mmHg) decreased by median [5th, 95th percentile] of -6.5 systolic [-27.0, 8.0] and -2.0 diastolic [-15.0, 8.0] (p < 0.001). Hypertensive patients with no weight loss or with weight gain had median decreases of -3.5 systolic [-26.0, 10.0] and -1.5 diastolic [-16.0, 9.0] (p < 0.001). Normotensive patients had median increases of 1.5 systolic [-15.0, 19.5] and 1.0 diastolic [-10.5, 13.0] (p < 0.001) attenuated with increasing weight loss. Approximately 43% of patients initially categorized as hypertensive had a lower blood pressure category at end-point. Concomitant antihypertensive medication classes did not affect blood pressure reductions. Pulse rates were uniformly elevated (median 1-4 bpm, p < 0.001) across blood pressure and weight change categories. CONCLUSIONS: In hypertensive patients (>or=140/>or=90), blood pressure decreases were observed during 6-week treatment with sibutramine even when body weight was unchanged. In patients with normal blood pressure (<130/<85), weight loss of >5% induced decreases in systolic blood pressure; otherwise, small increases were observed. Small pulse rate increases were observed regardless of blood pressure or weight change status.

Prevention of major venous thromboembolism following total hip or knee replacement: a randomized comparison of low-molecular-weight heparin with unfractionated heparin (ECHOS Trial).

AIM: Venous thromboembolism remains a frequent complication after total hip or knee replacement surgery despite routine prophylaxis. However, the ability of pharmacologic thromboprophylaxis to prevent major venous thromboembolism, defined as proximal deep vein thrombosis, and/or pulmonary embolism, and/or death, has not been previously validated. METHODS: In a double-blind randomized study, 2018 patients, undergoing either total hip or knee replacement surgery, were allocated to receive subcutaneous preoperative reviparin (4,200 anti Xa IU) once daily or 7,500 IU unfractionated heparin twice daily, for a minimum of 11 days. The primary efficacy outcome was major venous thromboembolism, defined as the composite of venographically confirmed proximal deep vein thrombosis, and/or symptomatic pulmonary embolism and death, recorded up to day 14. RESULTS: The primary efficacy outcome was assessed in 1,628 patients and demonstrated a significant reduction in the reviparin group (3.4% [28 of 813 patients] compared with unfractionated heparin (5.5% [45 of 815]) (odds ratio, 0.61; 95% confidence interval, 0.38 to 0.99, P=0.04) by day 11 to 14. A significant reduction in venous thromboembolism was maintained up to 6-8 weeks (3.4% [28 of 813 reviparin patients] versus 5.6% [46 of 815 unfractionated heparin patients]) (odds ratio, 0.6; 95% confidence interval, 0.37 to 0.97, P=0.03). Major bleeding events occurred in 9 reviparin-treated patients (0.9%) and in 12 unfractionated heparin-treated patients (1.2%). CONCLUSIONS: Prophylaxis with reviparin significantly reduces the risk of major venous thromboembolism compared with unfractionated heparin in patients undergoing elective hip or knee replacement without increasing the risk of bleeding.