Influence of age on the prescription of vitamin K antagonists in outpatients with permanent atrial fibrillation in France.

PURPOSE: The aim of the study was to describe the current rate and determinants of the prescription of antithrombotics in outpatients with permanent atrial fibrillation, with a pre-specified emphasis on the influence of age on the prescription of vitamin K antagonists. METHODS: This was a prospective observational survey in France among 5893 consecutive outpatients with documented permanent atrial fibrillation being seen by 770 physicians from August to December 2002. We recruited physicians from two random lists of general practitioners and cardiologists, respectively, stratified according to their administrative region, from the list of all French private general practitioners and cardiologists. RESULTS: The mean age of patients was 75.8 years. Mean duration since diagnosis of atrial fibrillation was 5.0 years; 31.7% of patients had valvular heart disease and 60.3% hypertension. An antithrombotic was prescribed to 95.5% of patients at the time of consultation. The percentage of patients treated with vitamin K antagonists was 76.4%; it decreased from 86.0% in patients aged 60-70 years to 63.5% in patients aged 80 years or above. On multivariate analysis, high age was a significant predictor (p = 0.001) for the non-prescription of vitamin K antagonists. In patients above 70 years currently receiving an antithrombotic, the probability of prescription of vitamin K antagonists decreased on average by 9.6% per year. CONCLUSIONS: Vitamin K antagonists are administered to most outpatients with permanent atrial fibrillation at high thromboembolic risk seen by French physicians in private practice. However, their use decreases with age.

Treatment of heart failure with celiprolol, a cardioselective beta blocker with beta-2 agonist vasodilatory properties. The CELICARD Group.

Treatment with beta blockers results in improvement in functional status, and reduces mortality in patients with heart failure. A number of differences in the results noted could be due to additional properties of the specific beta blockers studied: absence of cardioselectivity, and existence of a vasodilator effect and of an associated antioxidant effect. We studied the effects of celiprolol, a cardioselective beta blocker with a stimulant effect on beta2 receptors. One hundred thirty-two patients presenting with chronic heart failure of various etiologies, with an ejection fraction of <40% and New York Heart Association cardiac functional status grades II and III were included in a randomized, double-blind, placebo-controlled study. The maximum dose of celiprolol (100 mg) was attained after 1 month. The study lasted 1 year. The primary evaluation criterion was functional class as evaluated using the Goldman questionnaire. There was no difference in efficacy between the 2 treatment groups in terms of functional class (p = 0.56). With regard to the secondary evaluation criteria, an improvement in DiBianco functional score was seen with celiprolol (p = 0.03), as well as a significant reduction in heart rate (p = 0.01). Ejection fraction increased in both groups (p = 0.15). There was no difference regarding improvement in left ventricular volume as determined at echocardiography or in exercise capacity. The safety profile of celiprolol was excellent. There was no difference in terms of cardiovascular mortality (2 receiving celiprolol vs 4 placebo), onset of arrhythmias (2 receiving celiprolol vs 3 placebo), worsening of heart failure (26 receiving celiprolol vs 23 placebo), or noncardiovascular adverse events (9 receiving celiprolol vs 14 placebo). The absence of a significant efficacy of celiprolol, a beta blocker with vasodilator properties, but exerting stimulation of beta2 receptors, suggests an unfavorable role of this latter property in heart failure. However, the safety profile of celiprolol was excellent. This beta blocker may consequently be used for its other indications, hypertension and angina, in patients presenting with altered cardiac function.

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.

BACKGROUND: The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials. METHODS: In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months. RESULTS: The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant. CONCLUSIONS: Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.

Efficacy and safety of postdischarge administration of enoxaparin in the prevention of deep venous thrombosis after total hip replacement. A prospective randomised double-blind placebo-controlled trial.

Although venous thromboembolism has occasionally been reported after hospital discharge in patients who have undergone total hip replacement (THR), this risk has not been fully quantified and the usefulness of a prophylactic treatment has not been evaluated. We conducted a single-centre prospective randomised double-blind clinical trial in 2 parallel groups of patients who had undergone THR and were free of deep venous thrombosis (DVT) at discharge, as assessed by bilateral ascending venography. During hospitalisation, all patients received a low molecular weight heparin, enoxaparin (enoxaparin sodium), as a prophylactic treatment for venous thromboembolism. Just before hospital discharge (15 +/- 1 days from surgery) 179 consecutive patients were randomly assigned to receive subcutaneous enoxaparin 40mg (n = 90) or placebo (n = 89) once daily for 21 +/- 2 days. The primary efficacy outcome was defined as the occurrence of DVT and/or documented pulmonary embolism (PE). DVT was assessed by ascending bilateral venography performed 21 +/- 2 days after randomisation or earlier if necessary. Secondary efficacy outcomes were the occurrence of proximal and distal DVT. Safety outcomes were defined as the occurrence of major and minor haemorrhage, other adverse events and changes in laboratory parameters. All patients underwent a 3-month follow-up. There were no deaths or cases of clinical PE during the study and the follow-up periods. In 173 patients with evaluable venograms, analysis of efficacy on an intention-to-treat basis showed that the incidence of DVT at day 21 was significantly lower in the enoxaparin group (6 of 85; 7.1%) than in the placebo group (17 of 88; 19.3%; p = 0.018), a risk reduction of 63%. Distal DVT was less frequent in the enoxaparin group than in the placebo group (1.2 vs 11.4%; p = 0.006) but there was no significant difference between groups in the incidence of proximal DVT. A 'per-protocol' analysis of efficacy in 155 patients confirmed the results for total and distal DVT, but also showed a trend in efficacy in favour of enoxaparin with regard to the incidence of proximal DVT (p = 0.064). Enoxaparin was safe in comparison with placebo: only 2 minor bleedings occurred in the enoxaparin group and there was no difference in the incidence of other adverse events between the 2 groups. In patients undergoing THR, the risk of late-occurring DVT remained high during the 21 days after hospital discharge in the placebo group. Prophylactic treatment with enoxaparin reduced the risk and was well tolerated in this context.