Toschi V.,Thrombosis Center |
Lettino M.,Coronary Care Unit
British Journal of Clinical Pharmacology | Year: 2011
Cardiovascular diseases are still the most important cause of morbidity and mortality in western countries and antithrombotic treatment is nowadays widely used. Drugs able to reduce coagulation activation are the treatment of choice for a number of arterial and/or venous thromboembolic conditions. Some of the drugs currently used for this purpose, such as heparins (UFH or LMWH) and VKA, have limitations consisting of a narrow therapeutic window and an unpredictable response with the need of laboratory monitoring in order to assess their efficacy and safety. These drawbacks have stimulated an active research aimed to develop new drugs able to act on single factors involved in the coagulation network, with predictable response. Intense experimental and clinical work on new drugs has focused on synthetic agents, which could preferably be administered orally and at fixed doses. The most advanced clinical development with new anticoagulants has been achieved for those inhibiting FXa and some of them, like fondaparinux, are already currently used in clinical practice. Other agents, such as rivaroxaban, apixaban, otamixaban and edoxaban are under development and have already been studied or are currently under investigation in large scale phase III clinical trials for prevention and treatment of venous thromboembolism, atrial fibrillation and acute coronary syndromes. Some of them have proved to be more effective than conventional therapy. Data on some agents inhibiting FVa are still preliminary and some of these drugs have so far been considered only in patients with disseminated intravascular coagulation secondary to sepsis. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
Poli D.,Thrombosis Center |
Antonucci E.,University of Florence |
Testa S.,Haemostasis and Thrombosis Center |
Lip G.Y.H.,University of Birmingham
Internal and Emergency Medicine | Year: 2014
Stroke prevention, achieved with oral anticoagulation therapy (OAT), is central to the management of patients with atrial fibrillation (AF). Well-managed OAT, as reflected by a long time in therapeutic range (TTR), is associated with good clinical outcomes. The SAME-TT2R2 score has been proposed to identify patients who will maintain a high average TTR on vitamin K antagonists (VKA) treatment. The objective of the study was to validate this score in a cohort of AF patients followed by an anticoagulation clinic. We applied the SAME-TT2R2 score to 1,089 patients with AF on VKAs followed by two anticoagulation clinics. The median TTR overall for the whole cohort was 73.0 %. There was a significant decline in mean (or median) TTR in relation to the SAME-TT2R2 score (p = 0.042). When the SAME-TT2R2 scores were categorized we find a TTR 74.0 % for score ≤2 and 68.0 % for score >2 (p = 0.006). The rate of major bleeding events and stroke/TIA was 1.78 × 100 patient-years (pt-yrs) and 1.26 × 100 pt-yrs, respectively. No relationship exists between the SAME-TT2R2 score and adverse events. We describe the first validation of the SAME-TT2R2 score in AF patients where, despite an overall good quality of anticoagulation, the SAME-TT2R2 score is able to identify the patients who are less likely to do well on VKA therapy if this is the chosen OAT. © 2014 SIMI.
Lippi G.,Laboratory of Clinical Chemistry and Hematology |
Ardissino D.,Academic Hospital of Parma |
Quintavalla R.,Thrombosis Center |
Cervellin G.,Academic Hospital of Parma
Journal of Thrombosis and Thrombolysis | Year: 2014
The number of patients diagnosed with atrial fibrillation who will be candidates for antithrombotic therapy with direct oral anticoagulants (i.e., dabigatran, rivaroxaban, apixaban and edoxaban) is exponentially arising worldwide, thus posing substantial economic and organizational challenges for their urgent monitoring. Due to long turnaround time and inherent technical complexity, liquid chromatography techniques are unsuitable for rapid assessment of their concentration. Even the use of surrogate tests such as thrombin clotting time or anti-factor Xa activity carries some economic and technical drawbacks. Based on literature data, we have hence developed an algorithm based on first-line tests for urgent screening of the anticoagulant effect of direct oral anticoagulants, which entails activated partial thromboplastin time (aPTT) for dabigatran and prothrombin time (PT) for rivaroxaban. Although these tests also display a concentration-dependent prolongation in patients taking apixaban and edoxaban, neither of them is sufficiently sensitive for providing accurate estimation of the pharmacodynamic effect, so that the measurement of anti-factor Xa activity remains the most suitable approach in patients taking these drugs. According to literature data, this strategy appears suitable to reliably define the thrombotic or bleeding risk in an urgent setting, contextually saving precious laboratory resources. © 2014 Springer Science+Business Media.
Tosetto A.,S. Bortolo Hospital |
Iorio A.,McMaster University |
Marcucci M.,University of Perugia |
Baglin T.,Addenbrookes Hospital |
And 6 more authors.
Journal of Thrombosis and Haemostasis | Year: 2012
Background: In patients with unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulation is anchored on estimating the risk of disease recurrence. Objectives: We aimed to develop a score that could predict the recurrence risk following a first episode of unprovoked VTE, pooling individual patient data from seven prospective studies. Methods: One thousand eight hundred and eighteen cases with unprovoked VTE treated for at least 3months with a vitamin K antagonist were available for analysis. Optimism-corrected Cox regression coefficients were used to develop a recurrence score that was subsequently internally validated by bootstrap analysis. Results: Abnormal D-dimer after stopping anticoagulation, age <50years, male sex and VTE not associated with hormonal therapy (in women) were the main predictors of recurrence and were used to derive a prognostic recurrence score (DASH, D-dimer, Age, Sex, Hormonal therapy) showing a satisfactory predictive capability (ROC area=0.71). The annualized recurrence risk was 3.1% (95% confidence interval [CI], 2.3-3.9) for a score≤1, 6.4% (95% CI, 4.8-7.9) for a score=2 and 12.3% (95% CI, 9.9-14.7) for a score≥3. By considering at low recurrence risk those patients with a score≤1, life-long anticoagulation might be avoided in about half of patients with unprovoked VTE. Conclusions: The DASH prediction rule appears to predict recurrence risk in patients with a first unprovoked VTE and may be useful to decide whether anticoagulant therapy should be continued indefinitely or stopped after an initial treatment period of at least 3 months. © 2012 International Society on Thrombosis and Haemostasis.
Poli D.,Thrombosis Center |
Antonucci E.,University of Florence
International Journal of Women's Health | Year: 2015
Atrial fbrillation (AF) is the most common arrhythmia and has become a serious public health problem. Moreover, epidemiological data demonstrate that incidence and prevalence of AF are increasing. Several differences in epidemiological patterns, clinical manifestations, and incidence of stroke have been reported between AF in women and in men, particularly in elderly women. Elderly women have higher blood pressure than men and a higher prevalence of heart failure with preserved ejection fraction, both independent risk factors for stroke. On the basis of the evidence on the higher stroke risk among AF in women, recently, female sex has been accepted as a risk factor for stroke and adopted to stratify patients, especially if they are not at high risk for stroke. This review focuses on available evidence on sex differences in AF patients, and examines factors contributing to different stroke risk, diagnosis, and prognosis of arrhythmia in women, with the aim to provide an analysis of the available evidence. © 2015 Poli and Antonucci.