Efficacy of relaxin on functional recovery of post stroke patients.

BACKGROUND: Relaxin is a peptide hormone that exerts specific effects on cardiovascular system and human brain, leading to the hypothesis that this hormone may play a protective role against CVD and integration and modulation of behavioral activation. We aimed to demonstrate the efficacy of Relaxin on functional recovery of post-stroke patients. METHODS: Patients admitted within a Rehabilitation Unit suffering from stroke have been evaluated. Patients have been randomized to RLX (40 mcg/d) plus rehabilitation vs a control group that underwent only rehabilitation. A preliminary analysis of 36 patients at 20 and 40 days was made using the mRS for global function, the Functional Independent Measure (FIM) for daily activity and Trail Making Test (TMT) for cognitive function. RESULTS: Eighteen patients (age 72 (64-79), M 56%) randomized to RLX plus rehabilitation were compared to 18 patients (age 68 (64-78), M 50%) that underwent only rehabilitation. There was no difference between the two groups in terms of risk factors, stroke syndromes and etiology. At admission the two groups showed the same characteristics in terms of functional aspects (mRS, FIM; p ns) and cognitive function (TMT; p ns). After 20 days (T1) the treatment group (RLX+rehabilitation) showed no differences between the two groups (FIM 78 vs 69; p ns), while after 40 days (T2) patients treated with RLX+R showed an excellent recovery (FIM 96 vs 75; p0.001). In terms of cognitive function patients RLX+R revealed a better performance at T1 (TMT 3.5 vs 2; p 0.002) and still better at T2 (TMT 4 vs 2; p 0.001). These results have been confirmed in terms of global function both at T1 (mRS 2.5 vs 3; p0.001) and T2 (mRS 2 vs 3; p < 0.001). CONCLUSION: Relaxin showed in this analysis a positive effects on stroke patient's recovery, thus offering the broad therapeutic potential role of RLX as new drug in post-stroke patients.

Efficacy and safety of oral porcine relaxin (pRLX) in adjunct to physical exercise in the treatment of peripheral arterial disease (PAD).

INTRODUCTION: PAD medical therapy has a number of limitations. RLX showed promises in experimental model mainly through NO release. Our study is the first to evaluate the efficacy and safety of RLX in PAD. MATERIALS-METHODS: Eligible PAD La fontaine IIa-IIb patients were randomized in 2 groups. Group A was treated with physical therapy plus oral pRLX, 20 ug b.i.d for 12 weeks, group B received physical therapy alone. Pain Free Walking Distance (PFWD) and Maximum Walking Distance (MWD) at 3 and 12 wks and at follow up 3 months after treatment interruption were performed. RESULTS: The percentage increases of PFWD in group B were 23 +/- 9, 65 +/- 17, and 35 +/- 4 respectively at 3 and at 12 weeks, and 3 months after termination. In Group A showed significantly higher percentage increases: 74 +/- 16 p < 0.01, 168 +/- 28 p < 0.001, and 122 +/- 15 p < 0.001 at the corresponding time points. The percentage increases of MWD in the B group were 29 +/- 7, 55 +/- 10 and 54 +/- 8 at the above time points, while in the A group were 55 +/- 10 p < 0.001, and 99 +/- 12 p < 0.001. The RLX patients referred a better physical and mental status. No adverse events during or after the treatment were recorded. COMMENT: RLX resulted very effective in PAD. Our results may suggest that the observed functional benefits should come not only from hemodynamic improvement but also from positive vascular remodeling.

A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project.

SUMMARY BACKGROUND DATA: The epidemiology of venous thromboembolism (VTE) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis (DVT). However, the clinical relevance of asymptomatic venography-detected DVT is unclear, and the population of these clinical trials is not necessarily representative of the overall cancer surgery population. OBJECTIVE: The aim of this study was to evaluate the incidence of clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE. METHODS: @RISTOS was a prospective observational study in patients undergoing general, urologic, or gynecologic surgery. Patients were assessed for clinically overt VTE occurring up to 30 +/- 5 days after surgery or more if the hospital stay was longer than 35 days. All outcome events were evaluated by an independent Adjudication Committee. RESULTS: A total of 2373 patients were included in the study: 1238 (52%) undergoing general, 685 (29%) urologic, and 450 (19%) gynecologic surgery. In-hospital prophylaxis was given in 81.6% and postdischarge prophylaxis in 30.7% of the patients. Fifty patients (2.1%) were adjudicated as affected by clinically overt VTE (DVT, 0.42%; nonfatal pulmonary embolism, 0.88%; death 0.80%). The incidence of VTE was 2.83% in general surgery, 2.0% in gynecologic surgery, and 0.87% in urologic surgery. Forty percent of the events occurred later than 21 days from surgery. The overall death rate was 1.72%; in 46.3% of the cases, death was caused by VTE. In a multivariable analysis, 5 risk factors were identified: age above 60 years (2.63, 95% confidence interval, 1.21-5.71), previous VTE (5.98, 2.13-16.80), advanced cancer (2.68, 1.37-5.24), anesthesia lasting more than 2 hours (4.50, 1.06-19.04), and bed rest longer than 3 days (4.37, 2.45-7.78). CONCLUSIONS: VTE remains a common complication of cancer surgery, with a remarkable proportion of events occurring late after surgery. In patients undergoing cancer surgery, VTE is the most common cause of death at 30 days after surgery.

Direct thrombin inhibitors for the prevention of venous thromboembolism after major orthopaedic surgery.

Unfractionated heparin, low-molecular-weight heparins and vitamin K antagonists are established antithrombotic agents, but all have a number of limitations. Unfractionated heparin requires parenteral administration, has a short half-life and variable dose-response relationship. Low molecular weight heparins are more effective than low-fixed-dose unfractionated heparin in the prevention of postoperative venous thromboembolism in high-risk surgical patients but they still require subcutaneous administration. Vitamin K antagonists have a narrow therapeutic window and require a careful laboratory monitoring to minimize the risk of bleeding or thrombosis. Direct thrombin inhibitors are selective inhibitors of this key enzyme. Direct thrombin inhibitors inactivate thrombin without requiring any plasma cofactor, inhibit both free and fibrin-bound thrombin, and do not appreciably bind to plasma proteins. Ximelagatran, the first oral direct thrombin inhibitor, is rapidly absorbed and converted to its active form melagatran, which can itself be administered subcutaneously. Ximelagatran has been evaluated in the prevention of venous thromboembolism after major orthopaedic surgery, in the treatment of venous thromboembolism, in the prevention of stroke in patients with atrial fibrillation and in the prevention of recurrence after acute coronary syndromes. In the European studies in major orthopaedic surgery ximelagatran was administered orally after one or two days of melagatran, given subcutaneously. This review will report on the mechanism of action and clinical pharmacology of direct antithrombin agents and on the results of the clinical trials performed with direct thrombin inhibitors in the prevention of venous thromboembolism after major orthopaedic surgery. Taken together, these results indicate that direct thrombin inhibitors, ximelagatran in particular, have the potential to be a valid alternative to low molecular weight heparins and oral anticoagulants in the prevention of venous thromboembolism after major orthopaedic surgery.

Perspectives on antithrombotic agents: from unfractionated heparin to new antithrombotics.

BACKGROUND AND OBJECTIVES: Unfractionated heparin (UFH) has been the antithrombotic agent of choice for the prevention and treatment of venous thromboembolism (VTE) for a long time. UFH is also widely used for the treatment of patients with acute coronary syndromes. However, UFH has some limitations such as the need for parenteral administration and close monitoring of its anticoagulant effect. UFH is also associated with bleeding, heparin-induced thrombocytopenia and osteoporosis. EVIDENCE AND INFORMATION SOURCES: Low molecular weight heparins (LMWHs) are produced by the depolymerization of UFH. LMWHs have pharmacologic advantages over UFH: a better bioavailability after subcutaneous administration, a longer plasma half-life and a more predictable anticoagulant effect. These improved features allow once or twice daily subcutaneous injection of weight-adjusted doses of LMWHs without requiring laboratory monitoring in patients with VTE or unstable angina. PERSPECTIVES: A number of new antithrombotic agents are currently under development. These include direct antithrombins and factor Xa inhibitors. The results of the main clinical trials with LMWHs as well as those of the studies with the new antithrombotic agents will be reviewed in this article.