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Background: The MAS study (Blood Advances 2024) showed that a high proportion of Italian AF patients treated with direct oral anticoagulants (DOACs) receive reduced doses. This sub-analysis of MAS data aimed to analyze the effects of reduced (appropriate or not)- or standard-dose use on DOAC activity assessed at baseline and the occurrence of thrombotic or bleeding complications during follow-up., Methods: The MAS study design, the methods for DOAC measurement, the results, and the adverse events during follow-up, are described in detail elsewhere., Results: Seven hundred AF patients (42 % of the total 1657) received a reduced dose (considered inappropriate in 140 [20 %]). They were older, more frequently women, with lower body mass index (BMI), hemoglobin levels, and creatinine clearance. They more often had cerebral or cardiovascular diseases, were taking more medications, with higher scores for thrombotic or bleeding risk. Despite the use of low doses, 133 (19.0 %) patients had high standardized C-trough DOAC levels and experienced a high proportion of bleeding events (8.3 % per year). Conversely, some patients (4.7 %) had very low levels, resulting in a high incidence of thrombotic events (6.7 % per year). No difference was detected if the reduced dose was appropriate or not., Conclusion: The unpredictable, highly variable inter-individual anticoagulant effect of DOACs may lead to either too low or too high anticoagulant levels, increasing the risk of thrombotic or bleeding events. This is particularly relevant for patients with high-risk conditions, such as those chosen for reduced-dose treatment. Further studies are needed to investigate this important clinical issue., (Copyright © 2024. Published by Elsevier B.V.)

Some previous observations suggest that a low platelet count is associated with an increased risk of adverse outcomes in patients with acute coronary syndromes (ACS). However, most of the data come from post-hoc analyses of randomized controlled trials and from studies including thrombocytopenia developed during hospital stay. Our aim was to assess the impact of low platelet count at admission on cardiovascular outcomes and treatment approach in patients hospitalized for ACS in a current real-life setting in Italy. Patients admitted to Italian coronary care units for ACS were enrolled in the START-ANTIPLATELET registry. Baseline clinical characteristics and treatment at discharge were recorded. Patients were followed-up at 6 months, 1 year and yearly thereafter. Low platelet count was defined as a count at admission < 150 > 100 k/µl or < 100 k/µL. Among 1894 enrolled patients, 157 (8.3%) had a platelet count < 150 > 100 k/µl and 30 (1.6%) < 100 k/µl. The median follow-up was 12.3 months (0.4-50.1). patients with low platelets were older (72 ± 10.4 vs 66 ± 12.4 years, p = 0.006), more frequently males (82.9 vs 72.1%, p = 0.001), hypertensive (90.0% vs 70.4%, p = 0.03), with non-valvular atrial fibrillation (NVAF) (17.1 vs 8.6%, p = 0.02), and peripheral arterial disease (11.5 vs 6.2% p = 0.01) and/or had a previous myocardial infarction (40 vs 18.7%, p = 0.008) and/or a PCI (14.6 vs 7.8%, p = 0.001) than patients with normal platelets. A slightly, but significantly, lower percentage of thrombocytopenic patients were treated with primary PCI (78.1 vs 84.4%, p = 0.04) and they were more frequently discharged on aspirin plus clopidogrel rather than aspirin plus newer P2Y 12 antagonists (51.9 vs 65.4%, p = 0.01). MACE-free survival was significantly shorter in thrombocytopenic patients compared to patients with normal platelets (< 150 > 100 k/µl: 37.6 vs 41.8 months, p = 0.002; HR = 2.7, 95% CIs 1.4-5.2; < 100 k/µl: 31.7 vs 41.8 months, p = 0.01; HR = 6.5, 95% CIs 1.5-29.1). At multivariate analysis, low platelet count, age at enrollment, low glomerular filtration rate, low ejection fraction, a previous ischemic stroke and NVAF were independent predictors of MACE. A low platelet count at admission identifies a subgroup of ACS patients with a significantly increased risk of MACE and these patients should be managed with special care to prevent excess adverse outcomes., (© 2024. The Author(s).)

Background: DOACs are characterized by a higher incidence of gastrointestinal bleeding and this may be different among males and females. Female patients were underrepresented in the DOAC pivotal trials. We aimed to assess real-world differences in gastrointestinal bleeding with oral anticoagulants (DOACs and VKAs) among males and females with atrial fibrillation. Methods: We performed a population-based retrospective analysis on linked administrative claims. Atrial fibrillation patients of 65 years and above were considered. Bleeding risk factors were assessed through HASBED and previous history of gastrointestinal disease. A time-to-event analysis compared gastrointestinal bleeding between males and females. Results: The overall cohort consisted of 15338 (55% female) DOAC and 44542 (50% female) VKA users. Most of the patients showed HASBED ≥2. Incidence rate of GI bleeding was higher in females as compared to males among DOAC users (0.90% vs 0.59%), and significant gender difference in GI bleeding was found, after adjustment, in the Cox regression analysis (HR 1.48, 95%CI 1.02-2.16). In the VKA group, no significant difference among genders was found in the time-to-event analysis. Conclusions: Our data suggest that female patients treated with DOACs have a higher risk of GI bleeding versus male patients; this difference is not observed in VKA patients.

The risk of ischemic events carried by different clusters of type 2 diabetes mellitus (DM) in the setting of secondary prevention is not definite and the association between DM and bleeding complications is controversial. We explored these issues in the START-ANTIPLATELET, a multicenter Italian registry including acute coronary syndrome (ACS) patients. Study outcome was 1-year incidence of the net composite endpoint including major adverse cardiovascular events (MACE) or any bleeding and its individual components across different DM strata (no DM, DM with or without insulin). Out of 951 patients, 20.0% had diabetes not on insulin and 2.5% had diabetes on insulin. The rate of the net composite endpoint was highest in patients receiving insulin (39.4 per 100 person-years vs 11.7 in diabetic patients not on insulin vs 14.0 in those without DM; p = 0.007). In DM, the higher risk of MACE was regardless of insulin use (p = 0.36). Conversely, the increase in bleeding complications was limited to patients on insulin (Hazard Ratio 2.31, 95% CI 0.93-5.71 vs no DM; p = 0.0105 across DM strata). On top of aspirin, the rates of the net composite endpoint were similar with ticagrelor/prasugrel or clopidogrel irrespective of DM status (p for interaction 0.63). In conclusion, in ACS patients, type 2 DM enhances the risk of MACE regardless of the DM cluster, whereas the propensity to bleeding related to DM seems confined to insulin-treated patients., (© 2021. Società Italiana di Medicina Interna (SIMI).)

In the last decade, direct oral anticoagulants (DOACs) have entered the clinical practice of different specialists for the prevention of cardioembolic stroke in patients with non-valvular atrial fibrillation (NVAF) and the prevention and treatment of venous thromboembolism (VTE). Owing to the persistent uncertainties about the use of DOACs in daily clinical scenarios not fully explored in the clinical trials, we conducted a national Delphi consensus regarding issues deemed interesting by the Italian Atherosclerosis, Thrombosis and Vascular Biology (ATBV) Study Group in relation to: (i) elderly and/or frail patients; (ii) chronic kidney disease; (iii) drug-drug interactions; (iv) lower doses and safety; (v) criteria for choosing individual drugs and compliance; (vi) VTE in the cancer patient. Eighty-four Italian clinicians (cardiologists, internists, geriatricians, neurologists and hematologists) expressed their level of agreement on each statement using a 5-point Likert scale (1: very much in disagreement, 2: disagreement, 3: partial agreement, 4: agreement, 5: very much in agreement). In particular, 1-2 selections were considered as disagreement, while 3-5 selections were considered as agreement. A ≥66% agreement between the participants for each statement was considered consensus. In general, a broad and general awareness and sharing of the methods of use of DOACs emerged from our initiative, and in particular their preferential indication in the elderly population and in frail patients or with renal insufficiency or oncological, always following the prescription indications and dose reduction criteria. The importance of being aware of drug-drug interactions has also been underlined in a concordant way, as well as simplicity of treatment in the multi-treated patient. In view of the persistent, albeit limited (12%), absence of consensus on some issues, with regard to the frail patient, drug-food interactions and availability of antidote, the acquisition of further evidence and a persistent educational effort are nonetheless indicated.

Background: Coronavirus disease 2019 (COVID-19) global pandemic has strikingly high mortality rate with hypercoagulability state being part of the imputed mechanisms. We aimed to compare the rates of in hospital mortality in propensity score matched cohorts of COVID-19 patients in chronic anticoagulation versus those that were not., Methods: In this population-based study in the Veneto Region, we retrospectively reviewed all patients aged 65 years or older, with a laboratory-confirmed COVID-19 diagnosis. We compared, after propensity score matching, those who received chronic anticoagulation for atrial fibrillation with those who did not., Results: Overall, 4697 COVID-19 patients fulfilled inclusion criteria, and the propensity score matching yielded 559 patients per arm. All-cause mortality rate ratio was significantly higher among non-anticoagulated patients (32.2% vs 26.5%, p = 0.036). On time to event analysis, all-cause mortality was found lower among anticoagulated patients, although the estimate was not statistically significant. (HR 0.81, 95%CI 0.65-1.01, p = 0.054)., Conclusion: Among elderly patients with COVID-19, those on chronic oral anticoagulant treatment for atrial fibrillation seem to be at lower risk of all-cause mortality compared to their propensity score matched non-anticoagulated counterpart. This finding needs to be confirmed in further studies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Optimal dual antiplatelet therapy (DAPT) strategy in high-bleeding risk (HBR) patients presenting with acute coronary syndrome remains debated. We sought to investigate the use of clopidogrel versus ticagrelor in HBR patients with acute coronary syndrome and their impact on ischemic and bleeding events at 1 year. In the START-ANTIPLATELET registry (NCT02219984), consecutive patients with ≥ 1 HBR criteria were stratified by DAPT type in clopidogrel versus ticagrelor groups. The primary endpoint was net adverse clinical endpoints (NACE), defined as a composite of all-cause death, myocardial infarction, stroke, and major bleeding. Of 1209 patients with 1-year follow-up, 553 were defined at HBR, of whom 383 were considered eligible for the study as on DAPT with clopidogrel (174 or 45.4%) or ticagrelor (209 or 54.6%). Clopidogrel was more often administered in patients at increased ischemic and bleeding risk, while ticagrelor in those undergoing percutaneous coronary intervention. Mean DAPT duration was longer in the ticagrelor group. At 1 year, after multivariate adjustment, no difference in NACEs was observed between patients on clopidogrel versus ticagrelor (19% vs. 11%, adjusted hazard ratio 1.27 [95% CI 0.71-2.27], p = 0.429). Age, number of HBR criteria, and mean DAPT duration were independent predictors of NACEs. In a real-world registry of patients with acute coronary syndrome, 45% were at HBR and frequently treated with clopidogrel. After adjustment for potential confounders, the duration of DAPT, but not DAPT type (stratified by clopidogrel vs. ticagrelor), was associated with the risk of ischemic and bleeding events at 1 year.

Background: Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome., Objective: The aim of this paper is to report the events during the 2-year follow-up after the study closure., Methods: On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020., Results: Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005)., Conclusion: These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome., (© 2020 International Society on Thrombosis and Haemostasis.)

In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk-benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.

Given the high prevalence of preexisting cardiovascular diseases and the increased incidence of adverse cardiovascular events in patients hospitalized for SARS-CoV-2 infection, the identification of optimal antithrombotic approaches in terms of risk/benefit ratio and outcome improvement appears crucial in this setting. In the present position paper we collected current evidence from the literature to provide practical recommendations on the management of antithrombotic therapies (antiplatelet and anticoagulant) in various clinical contexts prevalent during the SARS-CoV-2 outbreak: in-home management of oral anticoagulant therapy; interactions between drugs used in the SARS-CoV-2 infection and antithrombotic agents; in-hospital management of antithrombotic therapies; diagnosis, risk stratification and treatment of in-hospital thrombotic complications.

Aims: To compare mortality between anticoagulated atrial fibrillation patients and general population and among anticoagulation specific categories [direct oral anticoagulants (DOACs) vs. vitamin K antagonists(VKA)]., Methods: This was a population-based study including all residents in the Veneto Region aged 18 years or older. Administrative claims from July 2013 to September 2017 were used to identify anticoagulation-naïve atrial fibrillation patients. Propensity score matching was employed to compare patients on new and old anticoagulants., Results: Overall, 17 225 patients on direct anticoagulants were 1 : 1 matched to patients on VKA (49% males, median age 77 years). Mortality was higher with respect to the general population by 22 and 39% among patients on direct anticoagulants and VKA, respectively. Mortality from intracranial hemorrhage in the direct anticoagulant group was similar to that in the general population [standardized mortality ratio: 1.06, 95% confidence intervals (CI) 0.76-1.48], whereas it almost doubled in VKA group (1.92, 95% CI 1.49-2.46). When directly compared with the VKA cohort, the risk of death from intracranial hemorrhage halved with DOACs (hazard ratio 0.56, 95% CI 0.37-0.84)., Conclusion: The mortality rate of anticoagulated atrial fibrillation patients is increased with respect to the general population, particularly among patients treated with VKAs. The mortality rate for intracranial bleeding with DOACs is similar to that observed in the general population.

The protective effect of obesity on mortality in acute coronary syndromes (ACS) patients remains debated. We aimed at evaluating the impact of obesity on ischemic and bleeding events as possible explanations to the obesity paradox in ACS patients. For the purpose of this substudy, patients enrolled in the START-ANTIPLATELET registry were stratified according to body mass index (BMI) into 3 groups: normal, BMI <25 kg/m 2 ; overweight, BMI: 25 to 29.9 kg/m 2 ; obese, BMI ≥30 kg/m 2 . The primary end point was net adverse clinical end points (NACE), defined as a composite of all-cause death, myocardial infarction, stroke, and major bleeding. In n = 1,209 patients, n = 410 (33.9%) were normal, n = 538 (44.5%) were overweight and n = 261 (21.6%) were obese. Compared to the normal weight group, obese and overweight patients had a higher prevalence of cardiovascular risk factors but were younger, with a better left ventricular ejection fraction and lower PRECISE-DAPT score. At 1-year follow-up net adverse clinical endpoints was more frequently observed in normal than in overweight and obese patients (15.1%, 8.6%, and9.6%, respectively; p = 0.004), driven by a significantly higher rate of all-cause death (6.3%, 2.6%, and 3.8%, respectively; p = 0.008), whereas no significant differences were noted in terms of myocardial infarction, stroke, and major bleeding. When correcting for confounding variables, BMI loses its power in independently predicting outcomes, failing to confirm the obesity paradox in a real-world ACS population. In conclusion, our study conflicts the obesity paradox in real-world ACS population, and suggest that the reduced rate of adverse events and mortality in obese patients may be explained by relevant differences in the clinical risk profile and medications rather than BMI per se., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications., Methods: We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy, including any therapeutic switching among DOACs. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression., Results: Naïve patients initiating direct oral anticoagulants for stroke prevention in NVAF identified in a 4.25-year period are 17,920. After one year, the persistence to the DOACs is 72.9%. Approximately 9.8% of the discontinuations are due to switch to vitamin k antagonists (VKAs). On multivariate analysis, factors negatively affecting persistence were female gender, age <65 years, renal disease and history of bleeding. On the other hand, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction., Conclusion: In this study of real world data, one out four naive patients stopped treatment with DOACs within 12 months. Some characteristics may identify patients with poor persistence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Despite great advances with the introduction of ticagrelor and prasugrel in the treatment of acute coronary syndromes (ACS), the risk of thrombosis and bleeding remains significant and affects the choice of clinicians in the treatment of the single patient. Large registries are effective tools to explore patterns of drug administration and adherence to guideline recommendations in real-world clinical practice., Methods: START- antiplatelet is a prospective, observational registry carried out by seven Italian cardiology institutions on patients admitted for ACS aimed to document the real world treatment of ACS patients, adding also data on 12-month follow-up. We present data on the first 1050 patients who have completed 1-year follow-up on a total of 1537 patients. Primary end-points were: 1) MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) including all-cause and cardiovascular mortality, non fatal MI, urgent revascularization, TIA and ischemic stroke; 2) Major and minor bleeding according to TIMI, GUSTO and ISTH classifications., Results: The dual antiplatelet treatment most prescribed was aspirin plus ticagrelor (47.9%) and aspirin plus clopidogrel (32.1%). At a mean follow-up was 335±131 days, both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality. Both prasugrel and ticagrelor do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel. Patients with monotherapy had significantly higher incidence of both ischemic stroke and major bleedings., Discussion: The analysis of the register has documented that both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality but both do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel., Competing Interests: The authors have declared that no competing interests exist.

Essentials Currently, DOACs are given at fixed doses and do not require laboratory monitoring. Direct oral anticoagulant-specific measurements were performed at trough and peak. Patients who developed bleeding events showed higher DOAC plasma levels at peak. This study suggests the need of a more accurate DOAC dose assessment., Background: Direct oral anticoagulants (DOACs) are administered at fixed dose. The aim of the study was to evaluate the relationship between DOAC C-trough or C-peak plasma levels and bleeding complications in patients with non-valvular atrial fibrillation (NVAF)., Methods: Five hundred sixty five consecutive naive NVAF patients were enrolled. The DOAC measurements at C-trough and at C-peak (available in 411 patients) were performed at steady state, within the first month of treatment. Major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and minor bleeding (MinB), occurring during 1 year of follow-up after blood sampling, were recorded. For each DOAC, interval of C-trough and C-peak levels was subdivided into four equal classes and results were attributed to these classes; the median values of results were also calculated., Results: Two hundred eight patients were on apixaban, 185 on dabigatran, and 172 on rivaroxaban. For 1-[qqqdeletezzz] year follow up for all patients, we observed: 19 MB (3.36%), 6 CRNMB (1.06%), and 47 MinB (8.31%). The prevalence of bleeding patients with anticoagulant levels in the upper classes of C-peak activity (II + III + IV) was higher than that in the lowest class. Normalized results of C-peak levels were higher in patients with bleeding than in those without bleeding., Conclusions: Bleeding complications during DOAC treatment were more frequent among atrial fibrillation (AF) patients with higher C-peak anticoagulant levels. In addition to a previous study that showed an increased risk of thrombotic complications in the patients with low C-trough levels, this study seems to indicate that patients with NVAF on DOACs would need a more accurate definition of their optimal therapeutic window., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

The epidemiology and management of patients with acute coronary syndromes (ACSs) have evolved. We aimed to describe recent demographics and therapeutic changes in the Italian ACS population. We analyzed data from 2 multicenter consecutive Italian registries (the EYESHOT [EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalised in iTalian cardiac care units] and START-ANTIPLATELET registries) enrolling patients with ACS between December 2013 and June 2016. An overall population of 3756 patients with ACS was enrolled: 2585 in the EYESHOT and 1171 in the START-ANTIPLATELET. Compared with the EYESHOT, patients in the START-ANTIPLATELET registry presented more frequently with ST-segment elevation myocardial infarction and were more often smokers and dyslipidemic (all P < .001) and had atrial fibrillation ( P = .018) but were less frequently aged ≥75 years and with a history of major bleeding (all P < .001). Analysis of treatment strategy showed a significant increase in the use of percutaneous coronary intervention, drug-eluting stents, dual antiplatelet therapy, and ticagrelor in the START-ANTIPLATELET (all P < .001), with a substantial decline in the proportion of patients conservatively managed and on clopidogrel at discharge ( P < .001). A lower rate of in-hospital events was recorded in the START-ANTIPLATELET compared with the EYESHOT. The START-ANTIPLATELET and EYESHOT registries provide consecutive snapshots in the contemporary management of patients with ACS in Italy, showing important changes in both demographic characteristics and treatment strategies.

Background: Intracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH., Purpose: Search for individual risk factors and bleeding risk scores (HAS-BLED, ATRIA and ORBIT) associated with ICHs in patients with atrial fibrillation treated with VKAs., Methods: This is a retrospective case-control study in a single Thrombosis Center. During a 7-year period, patients with nonvalvular atrial fibrillation (NVAF) who developed ICH during VKAs were identified as cases. Four control patients matched for gender, age and length of VKAs were assigned to each case. The association between considered risk factors and ICHs was evaluated using a linear logistic regression method and expressed as odds ratio. Receiver operator characteristic (ROC) curves to assess the predictive ability of bleeding risk scores HAS-BLED, ATRIA and ORBIT were also evaluated., Results: Fifty-one cases of ICH, most of whom were 80 years of age or older (72.5%), were retrieved from the Thrombosis Center's database. Compared to 204 controls, no individual risk factors were associated with ICH. Poor ability to predict ICH was also found using ROC curves (C-statistic for HAS-BLED, ATRIA, and ORBIT were 0.55, 0.53 and 0.54, respectively)., Conclusions: ICHs during VKA therapy preferentially occur in very elderly patients. The risk of ICH is not predicted by the commonly used risk scores., (© 2018 John Wiley & Sons Ltd.)

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272., (© 2018 by The American Society of Hematology.)

Background: Patients with a mechanical prosthetic heart valve implantation need to be treated with a vitamin K antagonist (VKA) due to a substantially high risk of thromboembolism. In this study we report data on patients with mechanical heart valves (MV), with the aim of evaluating the thromboembolic risk in relation to the type and site of implantation, quality of anticoagulation and risk factors associated with thromboembolism., Methods: Observational retrospective multicenter study among Centers affiliated to the Italian Federation of Anticoagulation Clinics (FCSA) on patients with MV implanted after 1990 and followed for the management of anticoagulation., Results: We analyzed 2357 patients with mechanical heart valves (55.2% males), followed for 24,081 years. During the follow-up, 164 thromboembolic events (0.67/100 pt-yrs) and 243 major bleedings (1.0/100 pt-yrs) occurred. The median Time in Therapeutic Range (TTR), calculated in all intended INR classes, was 60% (IQR 47-74%). The rates of thrombotic events were significantly higher in patients intended to stay at therapeutic ranges >INR 2.0-3.0. The presence of atrial fibrillation, history of thromboembolism and of mitral prosthesis were independently associated with thromboembolism. However, a bad quality of anticoagulation (TTR <47%, 25°percentile of our population) was not correlated with thromboembolism., Conclusions: A low rate of bleeding and thromboembolic events in patients with mechanical heart valves were found, despite the sub-optimal anticoagulation control. The thromboembolic risk was not associated with the low TTR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic renal failure (CRF) impairs prognosis in patients with acute coronary syndromes (ACS); the differential impact of CRF on ischemic and bleeding events in the setting of ACS is unclear. We explored the predictive role of CRF, identified by different equations for the glomerular filtration rate estimation, on the occurrence of the composite end point, including both ischemic cardiovascular and major bleeding (major adverse cardiovascular and bleeding events [MACBE]) at 1 year, and its components. We accessed each patients data from 718 participants in the prospective, multicenter, and START ANTIPLATELET registry, performed on patients with ACS. The ability to predict the risk of MACBE was modest and similar for Cockcroft-Gault, MDRD, and CKD-EPI equations (area under the curves: 0.55, 95% confidence interval [CI] 0.47 to 0.63; 0.53, 95% CI 0.45 to 0.61; 0.54, 95% CI 0.46 to 0.62; respectively, overall p = 0.63). The incidence of MACBE in patients with CRF was 12.6 versus 7.4 per 100 patients/year in those with preserved renal function (adjusted odds ratio [OR] 1.80, 1.02 to 3.20, p = 0.045); the absolute excess in events rate due to CRF was higher for ischemic events (3.5%) than for major bleeding (2.6%). The increased occurrence of MACBE was even greater in patients with CRF and concomitant anemia (OR 2.16) and in patients with severe CRF (OR 2.78). In conclusion, our study indicates that, in patients with ACS, CRF impairs the clinical outcome at 1 year, especially when severe and when is concomitant with anemia. CRF is associated with greater absolute increase of ischemic events than major bleeding., (Copyright © 2018. Published by Elsevier Inc.)

START-Register--Survey on anTicoagulated pAtients RegisTer--is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1 ± 1.1, CHADSVASc score was 3.1 ± 1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) <30 ml/min]. Moderate renal failure (CrCl 30-59 ml/min) was found in 1265 patients (39.5%). The analysis of the START-Register data shows that two-third of patients who started chronic anticoagulant treatment had NVAF, one-third of them was > 80 years with high prevalence of renal failure.

Background: Although their benefits are controversial, artificial nutrition and hydration are often administered as a form of basic care to terminally ill patients. An important reason for this may be that these treatments have strong emotional and psychological meanings., Aims: In the present article we investigated the opinions of Italian physicians and nurses on the administration of artificial nutrition and hydration to terminally ill patients with advanced dementia. We also investigated the antecedents of these opinions, considering feelings and thoughts related to death, ethical issues and training in palliative care., Method: A questionnaire was administered to Italian physicians (n=288) and nurses (n=763). We analyzed the percentages of agreement with the administration of artificial nutrition and hydration and, using multivariate logistic regressions, the possible antecedents of these opinions., Results: Agreement with the provision of artificial hydration was higher (73%) than for artificial nutrition (48%), suggesting that artificial hydration may be seen as a form of basic care. Agreement with their administration was generally lower among professionals in northern Italy working in geriatrics wards who had received training in palliative care. We also found that death-related feelings and thoughts and ethical issues played a different part for physicians and nurses., Conclusions: Our findings suggest that opinions concerning artificial nutrition and hydration not only derive from scientific background, but also relate to cultural, ethical, and psychological issues. Our results also reveal important differences between physicians' and nurses' opinions, providing useful information for interpreting and overcoming obstacles to the effective cooperation between these professionals.

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, particularly in the elderly. AF is considered an independent predictor of mortality and risk factor for stroke. AF-related stroke is usually severe and associated with a high rate of mortality and disability. Despite its prevalence, AF is a poorly known disease and it is underestimated by the general population. The aim of the Censis survey was to analyze the levels of AF knowledge and information in the Italian population and the level of AF risk awareness by general practitioners and AF patients., Methods: The survey included structured interviews with a sample of 1000 Italian citizens aged ≥18 years, 300 general practitioners, and 1200 AF patients., Results: The analysis confirmed low levels of knowledge of AF. In particular, the results showed that only one third of Italians know AF that is however perceived as a severe disease. In this subgroup, the risk of stroke associated with AF is known by 65%, but it is also widespread the wrong concept that AF is associated with an increased risk of myocardial infarction. The lack of knowledge of AF and its complications by the Italian population is due to educational gaps of general practitioners. In particular, only 50% of the Italian general practitioners perceive the thromboembolic risk of paroxysmal AF as comparable to that of permanent AF. In addition, there is an underuse of the scores for thromboembolic and hemorrhagic risk stratification recommended by current guidelines and a frequent use of antiplatelet therapy rather than oral anticoagulant therapy. There is also a low level of knowledge and awareness of the disease among AF patients. However, the majority of AF patients are aware of the importance of antithrombotic prophylaxis for stroke prevention., Conclusions: This study demonstrates limited knowledge and awareness of AF in the general population and also among general practitioners and affected patients.

Background and Aims: In Italy there is a paucity of empirical data on practices concerning end-of-life decisions (ELDs) in geriatrics. We aimed to investigate the frequency and characteristics of ELDs made by Italian physicians and nurses in the geriatric setting., Methods: In 2009, an anonymous questionnaire was sent to 54 geriatric units, 21 hospices, and 382 nursing homes in the Veneto and Trentino Alto Adige regions, and to professionals in the area who are members of the Italian Gerontology and Geriatrics Association., Results: This paper reports the results of 552 questionnaires answered by 171 physicians, 368 nurses and 13 professionals who did not state their profession. Death was preceded by decisions to start or continue treatments likely to prolong the patients' life in 51.3% of cases. The proportion of deaths preceded by a decision to end life (DEL) was 20.8%; 18% of DELs concerned non-treatment decisions. There were 9 cases of ending of life without patient's explicit request. No cases of doctor-assisted suicide were reported, while there were 2 cases of euthanasia, one reported by a physician and one by a nurse., Conclusion: In geriatrics, DELs often precede the deaths of terminally-ill Italian patients. Nurses report making DELs more often than physicians, especially in incompetent patients. Continuous deep sedation was adopted by 39.5% of the Italian physicians for deaths not occurring suddenly and unexpectedly. Our report on physicians' and nurses' experiences of ELD making in geriatric settings can offer a valuable contribution to the current debate on end-of-life treatment, an issue that goes beyond national borders.

Physicians are occasionally faced with difficult situations in the management of vitamin K antagonists (VKA) due to the lack of sound data available in controlled studies on certain conditions. In this review we would like to address some special but frequent conditions that can be encountered in daily clinical practice. These include the use of VKA in hemodialysis, thromboembolism in patients with liver cirrhosis and the thromboembolic risk in patients who bleed in the course of treatment with VKA. Moreover, two other conditions were examined: what the best way of expressing prothrombin time would be in patients with liver disease and how to behave when a patient treated with VKA shows a subtherapeutic INR. These topics were discussed by a panel of experts during a workshop recently held in Milan by the Italian Federation of Centres for the Diagnosis of Thrombosis and the Surveillance of Antithrombotic Therapies (FCSA). The main aim of the workshop was to provide helpful and practical advice to physicians in the daily management of VKA.

Within-individual biological variation of INR (CV(B)) was assessed in 245 selected stable warfarin-treated patients monitored by three thrombosis centers. Selection criteria were: treatment period of six months or longer before the observation period; at least six consecutive INRs within the therapeutic range of 2.0 - 3.0; interval between consecutive INR measurements of two weeks or longer; no change in warfarin dose; no changes in the patient's circumstances which may influence the INR, such as intercurrent diseases, invasive procedures, starting or stopping drugs interacting with warfarin. The minimum, maximum and mean within-individual coefficient of variation CV(B) of the INR measurements in the 245 selected patients were 0.4%, 14.5%, and 9.0%, respectively Analytical performance goals for the INR measurement (imprecision) could be derived from the mean CV(B). For a therapeutic range of 2.0 - 3.0 with warfarin, the desirable and optimum imprecision of INR determination is <4.5% CV and <2.25% CV, respectively. The biological variation and analytical performance goals have been derived using classic laboratory methods but should be applicable to point-of-care testing as well., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The optimal duration of anticoagulation after recurrent venous thromboembolism(VTE) is poorly established [1,2]. Recent studies suggested that D-dimer may identify patients at low risk of recurrence after a first VTE [3,4]. In a pilot, prospective, cohort study we aimed to assess the negative predictive value of D-dimer in patients with recurrent VTE. Patients with negative D-dimer while on treatment stopped anti coagulation and underwent repeated testing after 7, 15, and 30 days; treatment was resumed if D-dimer turned positive and permanently stopped if it remained negative. The study was interrupted after the enrolment of 75 patients. At that time, treating physicians decided treatment resumption in 12.2% of the patients, but the majority of events were distal or superficial vein thromboses. The rate of objectively documented recurrent proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) was 2.56% (95% CI 0.13, 15.07%) in the 39 patients with persistently negative D-dimer at 30 days, for an annual incidence of VTE of 5.65 events/100 patient/years. These preliminary findings suggest that negative D-dimer may identify patients with history of previous VTE at low risk of recurrences, but this approach should be tested in larger trials in highly selected patients.

Dabigatran and other new oral anticoagulants (OAC) represent a step forward in stroke prevention in patients with atrial fibrillation (AF). They indeed have been shown to be an alternative to vitamin K antagonists (VKAs) without the burden of laboratory control. However, these new drugs compete with an effective and well-established therapy, thus bringing about a series of questions and doubts. In this report members of the board of the Italian Federation of Thrombosis Centers (FCSA) answer some questions every clinician might be confronted with.

Objective: To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy., Methods: A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared., Results: The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-β(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies., Conclusion: It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.

Whether long-term use of vitamin K antagonists (VKAs) might affect the incidence of cancer is a longstanding hypothesis. We conducted a population-based study including all cancer- and thromboembolism-free patients of our health area; study groups were defined according to chronic anticoagulant use to VKA-exposed and control groups. Cancer incidence and cancer-related and overall mortality was assessed in both groups. 76 008 patients (3231 VKA-exposed and 72 777 control subjects) were followed-up for 8.2 (± 3.2) years. After adjusting for age, sex, and time-to-event, the hazard ratio of newly diagnosed cancer in the exposed group was 0.88 (95% confidence interval [95% CI] 0.80-0.98; P < .015). VKA-exposed patients were less likely to develop prostate cancer, 0.69 (95% CI 0.50-0.97; P = .008). The adjusted hazard ratio for cancer-related and overall mortality was 1.07 (95% CI 0.92-1.24) and 1.12 (95% CI 1.05-1.19), respectively. These results support the hypothesis that anticoagulation might have a protective effect on cancer development, especially prostate cancer.

Background: The characteristics and the clinical course of antiphospholipid syndrome (APS) in high-risk patients that are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described., Methods: This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL [lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein I (beta2GPI) antibodies]. Laboratory data were confirmed in a central reference laboratory., Results: One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow-up period was 12.2% (95% CI, 9.6-14.8) after 1 year, 26.1% (95% CI, 22.3-29.9) after 5 years and 44.2% (95% CI, 38.6-49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95% CI 1.3-4.1; P<0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths)., Conclusions: Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.

Background: In up to 80% of patients with pulmonary embolism (PE) no peripheral symptomatic thrombosis can be identified. Whether the heart may represent a source of PE is unknown., Methods: We conducted a cross-sectional survey of patients who were 60 years or older and were discharged from the hospitals of Veneto region, Italy between 2000 and 2006 with the diagnosis of PE. We compared the prevalence of several acute and chronic heart diseases in patients discharged with the diagnosis of PE alone with that of patients with co-occurring symptomatic peripheral deep venous thrombosis (PE/DVT)., Results: Out of 11,236 eligible patients, 9079 (81%) were discharged with the diagnosis of PE alone, and 2157 with that of PE/DVT. 3239 of the 9079 (35.7%) patients with isolated PE, and 666 of the 2157 (30.9%) with PE/DVT had at least one heart disease. The adjusted odds ratio (OR) for having at least one heart disease in patients with isolated PE as compared to those with PE/DVT was 1.26 (95% CI, 1.13-1.40). The heart diseases that significantly contributed to the study results were all-cause cardiomyopathies (adjusted OR, 2.31; 95% CI, 1.37-3.89), all-cause heart failure (1.82; 1.45-2.27), coronary heart disease (1.28; 1.08-1.52), and atrial fibrillation or flutter (1.28; 1.08-1.51)., Conclusions: There is an association between isolated PE and a number of heart diseases. The results of our survey generate the hypothesis that in older patients several heart diseases may directly account for the development of PE. Prospective studies are needed to confirm this hypothesis., (2009 European Federation of Internal Medicine.)

In the perioperative management of patients on long-term oral anticoagulant (OAC) therapy the problem is balancing the thromboembolic (TER) and the haemorrhagic risk (HR) in the perioperative period. The Federazione Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche (FCSA) activated an online registry from November 2001 to August 2003 in order to collect information on the management of these patients in Italy. Four hundred and eleven patients, undergoing elective major (18%) and minor surgery (82%), from 7 centres, were registered. Three hundred and ninety-nine out of 411 patients received LMWH either once a day (310 patients) or twice a day (89 patients) during OAC therapy discontinuation. Two thromboembolic (0.48%) and 16 bleeding events (7 major; 1.7%) were reported. Notwithstanding the lower doses of heparin (54.3 U/kg o.d. and 64.4 U/kg b.i.d.), the thromboembolic complications are in line with those reported in the literature. The data of this study suggest that the intervention with LMWH may be relevant only in the high-risk patients as already proposed by others.

Purpose: The purpose of our study was to analyse behaviours and patient-physician relationship about phytotherapy among a sample of Italian patients on warfarin therapy for atrial fibrillation., Methods: During a 4-month study period, interviews of patients on warfarin therapy, followed regularly in the medical laboratories to monitor INR values, were conducted on the basis of a pre-structured 25-item questionnaire., Results: Among a study population of 294 patients, 69 subjects reported to have been taking one or more phytotherapic products in the last year in combination with warfarin. Users were mostly in the age group >50 years and had a low level of education. Five out of 69 patients reported side effects, while 16/69 referred an unstable INR value. The majority of our subjects considered phytotherapy useful and without risks., Conclusions: The present survey highlights the potential risk of confidence with the 'natural world', the lack of discussion on this argument among health care providers and patients on warfarin therapy and the need to monitor strictly the INR value., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Background/objectives: Expert oral anticoagulation management is the key to good outcomes and is performed variably in different health care systems throughout the world. We set out to assess the quality of anticoagulation management in five countries in patients receiving vitamin K antagonists (VKAs) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF), and to compare the anticoagulation management practices in these countries., Methods and Results: This was a retrospective, multi-centre cohort study in the United States, Canada, France, Italy, and Spain. About 1,511 patients were randomly recruited from representative practices (routine medical care (RMC) in the US, Canada, and France; anticoagulation clinics in Italy and Spain) and data pertaining to their oral anticoagulation care were abstracted from their medical records. The predominant anticoagulant in use was warfarin in the US, Canada, and Italy; acenocoumarol in Spain; and fluindione in France. Documentation of care was poor in the US, Canada, and France, countries where RMC was studied. Percent INRs or time-in-therapeutic range was greater in the two anticoagulation clinic samples compared with the RMC samples., Conclusion: Oral anticoagulation care varies considerably from country to country. Findings suggest that anticoagulation clinic care (ACC) may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate. Condensed Abstract Oral anticoagulation management (routine medical care or anticoagulation clinic care) was retrospectively assessed in 5 countries using a uniform, structured assessment tool. Major management differences were detected, especially between anticoagulation clinic care and routine care. Documentation was often a problem in the latter setting. Less time in therapeutic INR range was noted in routine medical care. Findings suggest that anticoagulation clinic care may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate.

Background: Lupus anticoagulant (LA) screens are frequently ordered in the workup of thrombophilic patients or women with fetal loss. The sensitivity and specificity of LA detection vary depending on the choice of tests, cutoff values, and results interpretation. This variation is detrimental to patient management because persistent LA positivity in patients with a history of thrombosis is a requisite for long-term anticoagulation therapy. Numerous surveys have been performed to assess the state of the art for LA diagnosis. The control plasmas used in these surveys were from LA-positive or -negative patients or were normal plasmas with monoclonal antibodies against human beta(2)-glycoprotein I (beta(2)-GPI) added., Methods: A large number of laboratories were asked to test a common set of lyophilized plasmas for LA, including three normal plasmas, to which increasing amounts of affinity-purified IgG from a patient positive for anti-beta(2)-GPI had been added, and three LA-negative plasmas: one normal, one with a coagulation deficiency, and one with heparin., Results: Overall, 69, 68, and 59 of 70 participants were able to detect LA in plasmas with high, intermediate, and low potency (sensitivity, 99%, 97%, and 84%). Conversely, 69, 50, and 53 of 70 were able to rule out LA in the normal, heparinized, and deficient plasma (specificity, 99%, 71%, and 76%)., Conclusions: Sensitivity for LA detection is satisfactory, whereas specificity could be improved. Surveys for LA detection should be carried out on a regular basis because they may help improve performance. Plasmas containing graded amounts of affinity-purified human anti-beta(2)-GPI may be used as a convenient source of well-characterized naturally occurring LA material.

Background and Objectives: Self-testing and self-monitoring with portable prothrombin time (PT) monitors has been shown to be feasible and safe. However the ability of patients on chronic oral anticoagulant therapy (OAT) to self-adjust their dose without specific training has never been properly evaluated. The aims of this study were to evaluate: 1) the ability of patients on chronic OAT to self-adjust their dose without specific training; 2) the integration of a portable PT monitor (Coagucheck, Roche Diagnostics, Germany) for home use into routine patient care in anticoagulation clinics., Design and Methods: A nested case-control study was conducted in four centers of the Italian Federation of Anticoagulation Clinics (FCSA). Patients (n=78) on stable OAT for at least 6 months (cases: 47 men, 31 women, age range: 18-75 years) were enrolled on a volunteer basis after passing an Abbreviated Mental Test and providing informed consent. After three instruction sessions on the use of Coaguchek, subjects performed the PT test at home, communicated the INR results to the Center and suggested the dose adjustment and date for next control as they thought appropriate. However, they were requested to follow the prescription made by the Center. Controls (78 subjects) matched by age (+/- 5 years), sex and therapeutic range with the cases, were selected from among those who attended the anticoagulation clinics and managed by usual care., Results: When compared with the dose prescribed by the Clinic, the dose suggested by warfarin and acenocoumarol users was equal to or within +/- 6% of the mean weekly dose in 80% and 82% of suggestions, respectively. Time spent in the therapeutic range during the study was the same (80%) for cases and controls., Interpretation and Conclusions: Selected patients on chronic anticoagulant therapy can acquire a satisfactory ability for self-adjustment of OAT dose without specific training.

Background: Whether elderly patients are at increased risk of complications during oral anticoagulant treatment (OAT) is still a matter of debate., Method: Bleeding and thrombotic events occurring during OAT in 461 patients, aged 75 years or older when they started OAT, and in 461 patients younger than 70 years, matched for sex, OAT indication, and treating center, were examined in a prospective, multicenter, inception-cohort study., Results: Bleeding rate was 9.9% and 6.6% patient-years in elderly and young patients, respectively (P = .07), and 2.1% and 1.1% for major bleeding (P = .19); 6 and 1 events, respectively, were fatal (all intracranial, relative risk, 6.4; P = .05). In the elderly, bleeding rate was lower (4.5%) for international normalized ratios (INRs) between 2.0 and 2.9; it was higher during the first 90 treatment days (P = .05) and when arterial vascular disease was the indication for OAT (P = .03). Thrombosis rate was 4.2% and 2.5% patient-years in elderly and young patients, respectively (P = .10); however, 13 and 5 events were fatal (relative risk, 2.8; P = .04). Thrombosis rate was lower (1.5%) for INRs between 2.0 and 2.9; it was higher during the first 90 treatment days (P<.001) and 6 of 7 venous events occurred at lower than 2.0 INRs., Conclusions: A nonsignificant trend was noted toward a higher rate of both bleeding and thrombotic complications in elderly vs matched younger patients. Intracranial bleeding and fatal thrombotic events were significantly more frequent in the elderly. Our results also indicate that lower than 2.0 INRs do not preclude bleeding in the elderly nor offer adequate protection from thrombotic events. Moderate anticoagulation (2.0-3.0 INRs) in elderly patients seems the safest and most effective.

The paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.5 per 100 patient years) were recorded in 67 patients: 20 fatal (1%), 39 major (1.9%) and 11 minor (0.6%). 34/70 events occurred within the first 90 days of treatment (relative risk - at multivariate analysis - of < or =90 days vs. >90 = 20.6, C.I. 12.7-33.5; p <0.0001). The risk was higher in patients aged > or =70 y (1.62, C.I. 1.0-2.61; p <0.05), and when indication for anticoagulant treatment was peripheral/cerebral arterial disease (1.84, C.I. 1.01-3.36; p <0.05). The frequency of thrombotic events was 17.5% when international normalised ratio (INR) levels were < 1.5, decreasing to 2.3% for INRs within the 2-2.99 category (relative risk of INRs <2.0 vs. > or =2 = 1.88, C.I. 1.16-3.07; p <0.05). The recorded rate of thrombotic events was lower than that reported in the few available studies. A greater risk should be expected during the first 90 days of treatment, when anticoagulation levels are <2.0 INR, in patients > 70 years and in those with cerebrovascular/peripheral arterial disease.

Background: To assess the incidence of bleeding complications during oral anticoagulant therapy (OAT) in a population of patients representative of daily practice in Italian anticoagulation clinics., Design: prospective, inception-cohort, multicentre., Setting: Thirty-four anticoagulation clinics federated in the Italian Federation of Anticoagulation Clinics., Patients: 2745 consecutive patients, included from beginning of their first OAT course. Most patients were aged between 60 and 79 y (57.8%), with 8% being > or = 80 y. Venous thromboembolism was the most frequent indication for OAT (one third of all the patients), followed by non ischemic heart disease which mainly included atrial fibrillation (16.8% of patients). Warfarin (in 63.8% of patients) and acenocoumarol were the only anticoagulant drugs used. The targeted anticoagulation intensity was low (INR < or = 2.8) in 71% of patients and high (INR > 2.8) in the remainder., Outcomes: Fatal, major and minor bleeding events. Thrombotic events were also recorded, though not analyzed in the present report., Findings: During the 2011 patient-years (pt-y) of follow-up, 153 bleeding complications (7.6% pt-y) were recorded--5 fatal (all cerebral haemorrhages, 0.25% pt-y), 23 major (1.1% pt-y) and 125 minor (6.2% pt-y). The rate of events did not vary according to sex, coumarin type, size of enrolling centre or targeted therapeutic range; it was higher in older patients (10.5% pt-y in those aged > or = 70 y, relative risk--RR--1.75, p < 0.001), in cases where indication for anti-coagulant treatment was peripheral and/or cerebrovascular disease (12.5% pt-y; RR 1.80, p < 0.01) and during the first 90 days of treatment (11% pt-y, RR 1.75, p < 0.001). One fifth of bleeding events occurred at a very low anticoagulation intensity (INR < 2; the category rate being 7.7% pt-y); the rate was 4.8% pt-y in the 2.0-2.9 INR category, reaching 9.5% pt-y, 40.5% pt-y and 200% pt-y in the 3-4.4, 4.5-6.9 and > or = 7 INR categories respectively (RR for INR levels > 4.5 = 7.91, p < 0.0001)., Conclusions: The overall rate of bleeding events recorded in the present study was much lower than that recorded in other (including recent) observational and experimental studies. The risk of bleeding increased in the following cases: age > 70 y; arterial vascular disease as indication for OAT; first 3 months of treatment; INR values > or = 4.5. OAT has become safer in recent years, particularly if monitored in special anticoagulation clinics. Caution should be exercised when prescribing OAT in elderly patients and the intensity anticoagulation levels should be closely monitored to minimize incidental periods of overanticoagulation.

Background: Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics., Methods: In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories., Findings: 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001)., Interpretation: We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

In patients with artificial heart valve prosthesis oral anticoagulants reduce but not eliminate the thromboembolic complications however, they do increase the risk of bleeding. In the present study, the incidence of thromboembolic and hemorrhagic complications in two homogeneous groups of patients with artificial heart valves on long term oral anticoagulant treatment has been evaluated. Group A (99 patients; total follow-up = 309 years) were resident in the Triveneto regions and received a questionnaire while group B (104 patients; total follow-up = 370 years) were referred to our department's centre for the control of oral anticoagulant treatment. Both groups were kept at a therapeutic range of 20-30% in terms of prothrombin activity. The incidence of thromboembolic and hemorrhagic complications is expressed as the number of episodes per 100 patient/years. Thromboembolic episodes were 2.6 (1.3 fatal) in group A while they were 1.08 (0.27 fatal) in group B; the reduction of fatal thromboembolic events was statistically significant (p less than 0.05). Hemorrhagic episodes were 1.9 (0.63 fatal) in group A while they were 0.81 (0 fatal) in group B. We concluded that an organized control of oral anticoagulant treatment in patients with artificial heart valves is advantageous as it significantly reduces fatal thromboembolism. Moreover, it could reduce the incidence of total thromboembolic and hemorrhagic episodes by more than 50%.