No abstract

Background-The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence. This study evaluated interventions for implementing a new practice guideline advocating the use of ␤-blockers for heart failure patients. Methods and Results-This was a randomized controlled trial involving heart failure patients (nϭ169) with an ejection fraction Յ45% and no contraindications to ␤-blockers. Patients' primary providers were randomized in a stratified design to 1 of 3 interventions: (1) control: provider education; (2) provider and patient notification: computerized provider reminders and patient letters advocating ␤-blockers; and (3) nurse facilitator: supervised nurse to initiate and titrate ␤-blockers. The primary outcome, the proportion of patients who were initiated or uptitrated and maintained on ␤-blockers, analyzed by intention to treat, was achieved in 67% (36 of 54) of patients in the nurse facilitator group compared with 16% (10 of 64) in the provider/patient notification and 27% (14 of 51) in the control groups (PϽ0.001 for the comparisons between the nurse facilitator group and both other groups). The proportion of patients on target ␤-blocker doses at the study end (median follow-up, 12 months) was also highest in the nurse facilitator group (43%) compared with the control (10%) and provider/patient notification groups (2%) (PϽ0.001). There were no differences in adverse events among groups. Conclusions-The use of a nurse facilitator was a successful approach for implementing a ␤-blocker guideline in heart failure patients. The use of provider education, clinical reminders, and patient education was of limited value in this setting. (Circulation. 2003;107:2799-2804.)

Vitronectin (VN) binds to plasminogen activator inhibitor-1 (PAI-1) and integrins and may play an important role in the vascular response to injury by regulating fibrinolysis and cell migration. However, the role of VN in the earliest response to vascular injury, thrombosis, is not well characterized. The purpose of this study was to test the hypothesis that variation in vitronectin expression alters the thrombotic response to arterial injury in mice. Ferric chloride (FeCl3) injury was used to induce platelet-rich thrombi in mouse carotid arteries. Wild-type (VN +/+, n = 14) and VN-deficient (VN −/−, n = 15) mice, matched for age and gender, were studied. Time to occlusion after FeCl3 injury was determined by application of a Doppler flowprobe to the carotid artery. Occlusion times of VN −/− mice were significantly shorter than those of VN +/+ mice (6.0 ± 1.2 minutesv 17.8 ± 2.3 minutes, respectively, P < .001). Histologic analysis of injured arterial segments showed that thrombi from VN +/+ and VN −/− mice consisted of dense platelet aggregates. In vitro studies of murine VN +/+ andVN −/− platelets showed no significant differences in ADP-induced aggregation, but a trend towards increased thrombin-induced aggregation in VN −/− platelets. Purified, denatured VN inhibited thrombin-induced platelet aggregation, whereas native VN did not. Thrombin times of plasma from VN −/− mice (20.5 ± 2.1 seconds, n = 4) were significantly shorter than those ofVN +/+ mice (34.2 ± 6.7 seconds, n = 4, P < .01), and the addition of purified VN to VN −/− plasma prolonged the thrombin time into the normal range, suggesting that VN inhibits thrombin-fibrinogen interactions. PAI-1-deficient mice (n = 6) did not demonstrate significantly enhanced arterial thrombosis compared with wild-type mice (n = 6), excluding a potential indirect antithrombin function of VN mediated by interactions with PAI-1 as an explanation for the accelerated thrombosis observed in VN−/− mice. These results suggest that vitronectin plays a previously unappreciated antithrombotic role at sites of arterial injury and that this activity may be mediated, at least in part, by inhibiting platelet-platelet interactions and/or thrombin procoagulant activity.

Cardiology care at this early stage of HF is associated with improved guideline adherence and a reduced risk of the composite outcome of death plus cardiovascular hospitalization.