Objectives We sought to evaluate the rate of bleeding in relation to age (<80 and ≥80 years), the quality of anticoagulation (expressed as time spent in international normalized ratio therapeutic ...range), and factors associated with bleeding events. Background Stroke prevention in patients with atrial fibrillation (AF) is an increasingly crucial public health target, particularly in patients ages ≥80 years. Methods We conducted a prospective observational study on 783 patients with AF on oral anticoagulant treatment (OAT). Results Patients spent a median 14%, 71%, and 15% of time below, within, and above the intended therapeutic range, respectively. No difference in OAT quality was found between patients age <80 and ≥80 years. During follow-up, 94 patients experienced bleeding complications (rate 3.7 × 100 patient/years), 37 major (rate 1.4 × 100 patient/years), and 57 minor (rate 2.2 × 100 patient/years). Different rates of major hemorrhage were observed between patients age <80 and ≥80 years (0.9 vs. 1.9 × 100 patient/years; p = 0.004). Bleeding risk also was greater in patients with a history of previous cerebral ischemic event (odds ratio OR: 2.5; 95% confidence interval: 1.3 to 4.8; p = 0.007). A Cox regression analysis confirmed age ≥80 years associated with bleeding risk (OR: 2.0). Conclusions These results indicate that the rate of major bleeding complications may be kept acceptably low also in very elderly AF patients on OAT, provided a careful management of anticoagulation is obtained.
Summary
The efficacy of adjusted-dose oral anticoagulant treatment (OAT) in the prevention of stroke in atrial fibrillation (AF) is well documented. Available data show that AF patients are widely ...heterogeneous in terms of ischaemic stroke risk. The role of female gender as a predictor of stroke risk is inconsistent, in particular it is unclear if warfarin treatment is able to prevent stroke equally in both sexes. We performed a prospective study on 780 AF patients on OAT, followed by an Anticoagulation Clinic, to evaluate if female gender is a risk factor for stroke among patients on OAT and if the quality of anticoagulation is different between genders. No difference was found in relation to the quality of anticoagulation between genders (p=0.5). During follow-up 33 patients had major bleedings (rate 1.37x100 pt/yrs) but no difference was found between genders in bleeding risk. Forty patients had ischaemic events rate 1.66x100 pt/yrs; males rate 1.2 x100 pt/yrs; females rate 2.43x100 pt/yrs; p=0.042; relative risk (RR) of females vs. males 2.0 (95% confidence interval CI 1.3–3.1); p= 0.004. The higher rate of ischaemic events in females with respect to males was confirmed at Cox regression analysis after correction for age (p=0.009). In addition, strokes occurring in females were more disabling, and RR for severe and fatal stroke, defined according to Modified Rankin scale, of females vs. males was 3.1 (95% CI 1.3–6.5; p=0.001). In conclusion, our data show a higher risk of stroke in anticoagulated AF females with respect to males, despite a similar quality of anticoagulation.
Stroke Risk Stratification. Introduction: Appropriate stroke risk stratification is essential to ensure suitable tailoring of antithrombotic therapy. The objective of this study was to assess the ...predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation (AF) who are at substantial risk of stroke despite optimal anticoagulant therapy, in a “real world” consecutive elderly AF cohort.
Methods: Six hundred and sixty‐two consecutive AF patients (mean SD age 74 7.7 years; 36.1% female) referred to the Anticoagulation Clinic of the Azienda Ospedaliera Careggi of Florence, Italy, were included and followed‐up for a mean 3.6 ± 2.7 years for the incidence of thromboembolic (TE) events. The ability of the new CHA2DS2‐VASc schema to predict TE was compared with other contemporary stroke risk schema (including CHADS2, NICE 2006, ACC/AHA/ESC 2006, and ACCP 2008), by determining the c‐statistic.
Results: Univariate predictors of TE events were female gender (odds ratio 1.9; 95%CI confidence intervals 1.01–3.70) and previous stroke/transient ischemic attack (TIA)/TE (OR 5.6; 95%CI 2.70–11.45), although after adjustment only previous stroke/TIA/TE was an independent predictor of TE (OR 5.5; 95%CI 2.68–11.31; P = 0.0001). All stroke risk schema had modest discriminating ability, with c‐statistics ranging from 0.54 (atrial fibrillation investigators AFI) to 0.72 (CHA2DS2‐VASc). The CHADS2 and CHA2DS2‐VASc schemes having the best c‐statistics (0.717 and 0.724, respectively) with significant discriminating value between risk strata (both P < 0.001). The proportion of patients assigned to individual risk categories varied widely across the schema, with those categorized as “moderate‐risk” ranging from 5.3% (CHA2DS2‐VASc) to 49.2% (CHADS2‐classical).
Conclusion: In this “real world” cohort, current published risk schemas have modest predictive ability, with the CHADS2 and CHA2DS2‐VASc schemes having the best predictive value for thromboembolism. Future trials could assess the value of alternative strategies for thromboprophylaxis in high‐risk anticoagulated patients identified by these schemes. (J Cardiovasc Electrophysiol, Vol. 22, pp. 25‐30, January 2011)
The optimal management of oral anticoagulation (OAC) in the acute phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains controversial, especially in very old ...patients. Therefore, the aim of our study was to evaluate the practical management of OAC in this context. We conducted an observational retrospective study on patients 85-years old and older admitted to two Italian hospitals for NVAF-related AIS. For each patient, clinical and brain computed tomography data were recorded. Type of OAC (vitamin K antagonists, VKAs or Direct Oral Anticoagulants, DOACs), dosage and starting day after AIS were registered. For each patient 90-day all cause mortality, stroke recurrence, any bleeding and modified Rankin scale (mRS) were reported. One-hundred-seventeen patients, with mean age 89.2 ± 3.4 years, were enrolled. In-hospital and 90-day mortality (out of 109 patients) were 6% and 19.7%, respectively. OAC was started in 93 patients (80.5%), on average after 6 ± 3 days from the acute event. Of them, 88 patients (94.6%) received DOACs, while 5 (5.4%) received VKAs. Patients receiving OAC were significantly younger and suffering from less severe stroke compared with patients who did not receive OAC. Patients receiving OAC presented a reduced in-hospital (2.2% vs. 20.8%, p < 0.004) and 90-day all-cause mortality (9.4% vs. 62.5%, p < 0.001). In patients receiving DOACs, low dosages were used in 87.5% of patients. The use of OAC was not associated with an increased rate of hemorrhagic transformation (HT) during hospitalization (13.2% vs. 9.5%, p = 0.54) or any bleeding at 90-day follow-up. Severe dysphagia and mRS ≥ 4 were found to be independent risk factors for not prescribing OAC. The optimal management of OAC in very old patients suffering from NVAF-related AIS remains a dilemma. In our real world study the majority of patients received OAC as secondary prevention treatment without increase in bleeding risk. Dysphagia and severe disability were independent factors for not prescribing OAC. Further investigations aimed at identifying the optimal approach to OAC during the acute phase of NVAF-related ischemic stroke in this subgroup of patients are warranted.
After a first episode of pulmonary embolism (PE), two major problems need to be considered: risk of recurrence when anticoagulation is stopped, and risk of chronic thromboembolic pulmonary ...hypertension (CTPH). We followed prospectively consecutive patients who survived a first episode of PE, with or without deep vein thrombosis, to assess the incidence of venous thromboembolism (VTE) recurrences and of symptomatic and asymptomatic CTPH. After 3–6 months of oral anticoagulant therapy (OAT) patients underwent transthoracic echocardiography for measuring transtricuspid (rV-rA) gradient. When rV-rA gradient was >35 mmHg further evaluations were performed to rule in or out CTPH. During follow-up patients who developed persistent dyspnea were re-evaluated. In patients who underwent OAT withdrawal D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), and thrombophilia were evaluated one month after warfarin discontinuation. Overall, 239 patients, 118 males, median age 59(16–89) years, were followed up for a median time of 36(9–192) months. Nine patients had rV-rA gradient >30 mmHg and ≤35 mmHg, and one of 37 mmHg. Among patients with normal rV-rA gradient, one developed persistent dyspnea 55 months after the first event and CPTH was confirmed. Among 206 patients who stopped OAT, 23(11.2%) had VTE recurrence, 11 PE(48%). Elevated DD and F1 + 2 levels after stopping OAT were significantly associated with recurrence. None of patients with recurrent VTE had elevated rV-rA gradient. In our series the incidence of CTPH after a first episode of PE was 0.4%. VTE recurrence and elevated DD and F1 + 2 levels seemed not to be related to the development of CTPH.
Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is lacking, because this kind of ...patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. In the latest years a lot of real life studies on this topic have been published. The aim of our review was to focus on these. We reviewed the PubMed databases searching articles reporting on DOACs starting time within 2 weeks from AIS onset. We selected fifteen studies, eight with retrospective, six with prospective observational and one with a prospective, open-label, single arm design. Overall, 2920 patients (47.8% females) were included. In twelve studies median or mean age of patients was over 75 years. Mean or median NIHSS ad hospital admission was ≤ 12 in all studies. About one-third of patients (32.4%) received urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. About one-fifth of patients (22.8%) had large infarct size. Median starting time of DOACs was reported in thirteen studies and it ranged from 2 to 8 days. About one-half of patients (45.9%) received a low dose of DOACs. In studies reporting on median or mean CHA
2
DS
2
-VASC score, it was ≥ 3 in all. In studies reporting on median or mean HAS-BLED score, it was ≥ 2 in all. Ninety-day follow-up was available for nine studies, overall including about 2200 patients. Incidence of 90-day TIA/stroke recurrence, symptomatic haemorrhagic transformation or intracranial bleeding and all cause mortality was 2.25%, 0.90% and 1.5%, respectively. The real life evidence suggests that early starting of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality.
Objective To investigate lipoprotein(a) Lp(a), a well known cardiovascular risk factor, in women with history of placenta-mediated pregnancy complications (PMPC) compared with healthy ...uneventful-pregnancy women (HW), and the role of LPA gene functional polymorphisms in modulating both Lp(a) levels and PMPC risk. Design Retrospective observational study. Setting University hospital. Patient(s) A total of 360 women with history of PMPC (154 preeclampsia PE, 121 stillbirth SB, and 85 small for gestational age SGA) and 270 HW. Intervention(s) Not applicable. Main Outcome Measure(s) Lp(a) levels measurement and LPA +93C >T and +121G>A polymorphisms genotyping. Result(s) In PMPCs we observed higher Lp(a) levels than those found in HW and an association with PMPC risk, also after adjustment for age, familial history of cardiovascular disease, and traditional risk factors. By analyzing Lp(a) concentrations according to each pregnancy complication, we observed significantly higher Lp(a) levels in women with history of SB and PE, conferring 2.5-fold and 2-fold increased risks, respectively; no association with SGA was observed. Lp(a) concentrations progressively and significantly increased as LPA unfavorable allelic burden increased; unfavorable allelic burden influenced SB and PE risk. Conclusion(s) We evidenced, for the first time, an association between high Lp(a) concentrations and history of SB, and we confirmed the role of Lp(a) in PE risk; this well known atherothrombotic marker might represent one of the possible mechanisms shared by PMPC and cardiovascular disease.
Few data are available on age-related burden and characteristics of embolic stroke of undetermined source (ESUS) in the real world clinical practice. The aim of our study was to provide information ...about it. We retrospectively analyzed data of patients consecutively admitted to our Stroke Unit along 1 year (2017, November 1st–2018, October 31st). The etiology of ischemic stroke was defined at hospital discharge; ESUS was considered as a subset of cryptogenic stroke, and defined according to the 2014 international criteria. In the analyzed period, 306 patients, 52.3% females, mean age ± SD 77.9 ± 11.9 years, were discharged with diagnosis of ischemic stroke. Ischemic strokes of cardioembolic and lacunar origin were the most frequent subtypes: 30.1% and 29.4%, respectively. Cardioembolic strokes were particularly frequent in patients ≥ 75 years, and almost always associated with atrial fibrillation. Overall, in 80 patients (26.1%) the etiology of stroke was undetermined; in 25 (8.2%) it remained undefined because of death or severe comorbidity, making further diagnostic work-up not worthy. Cryptogenic stroke occurred in 55 patients (18%), and ESUS criteria were satisfied in 39 of them (12.7%). According to age, cryptogenic stroke was diagnosed in 21.1% (21.1% ESUS) of patients < 65 years, 24.2% (19.4% ESUS) of patients aged 65–74 years, 15.5% (9.2% ESUS) of patients ≥ 75 years. After diagnostic work-up, patent foramen ovale was most commonly associated with ESUS (17.9%), especially in patients < 65 years (62.5%); covert paroxysmal atrial fibrillation was detected in 10.5% of ESUS patients ≥ 75 years. In the real world clinical practice, the frequency of ischemic strokes of undetermined etiology, and of those satisfying ESUS criteria, is not negligible, especially in younger patients. A thorough diagnostic work-up, with an age-specific approach, is therefore necessary and of the utmost importance for the identification of stroke etiology, in order to optimize secondary stroke prevention strategies.
Atrial fibrillation (AF) patients are widely heterogeneous in terms of ischaemic stroke risk, and several risk stratification schemes have been developed. We performed a prospective study on 662 AF ...patients on long-term oral anticoagulant therapy (OAT), evaluating the agreement among the different schemes and their correlation with adverse events recorded during follow-up. Patients at low risk were similarly distributed among the different models. Instead, patients classed at moderate risk were 49.2% by CHADS(2) score, 27.6% by NICE and 2.3% by ACCP. As a consequence patients classed at high risk were 46.1% by CHADS(2), 69.8% by NICE and 95.3% by ACCP. CHADS(2 )and NICE scores were associated to the best predictive accuracy. A separate analysis was performed for patients on treatment for secondary prevention, and we observed that they were included in high risk groups by all models, except for 14 patients (6.3%) classed at moderate risk by CHADS(2) even though these patients are at very high risk and the use of aspirin could be unsafe for them. During follow-up 32 major bleeding (1.35 per 100 patient/years) and 39 thrombotic events (1.64 per 100 patient/years) were observed. Among patients on OAT for secondary prevention, both bleeding and thrombotic events mostly occurred in high-risk patients. Even if the absolute rate of adverse events is low, this finding seems to confirm the high stroke risk of this group of patients. For patients on secondary prevention there is no need for further stratification and warfarin should be the treatment of choice.
Abstract
Introduction
Few data exist on the use of edoxaban in cancer-associated venous thromboembolism (VTE) outside of clinical trials. Aim of this study was to evaluate the characteristics and ...outcomes of these patients in a real world clinical setting.
Methods
We retrospectively analyzed the characteristics of patients with cancer-associated VTE who were prescribed edoxaban. Follow-up at 3, 6, and 12 months was performed: VTE recurrences, bleedings, mortality, cancer progression and treatment, edoxaban interruption and its reason were assessed.
Results
Fifty-four patients, 38 females (70.4%), mean age 71 ± 14 years, were enrolled. In 38 patients (70.4%), the episode of VTE was the first one, in 28 (51.8%) it was an isolated deep vein thrombosis (DVT), in 13 (24.1%) a pulmonary embolism (PE) associated with DVT, in 13 (24.1%) an isolated PE. Median time between cancer and VTE diagnosis was 6 (interquartile range IQR 2–47) months. Median time between VTE diagnosis and edoxaban prescription was 36 (IQR 7–117) days. At 3, 6, and 12 months the incidence of all-cause mortality was 16.6, 22.2, and 38.8%, that of VTE recurrence 1.8, 1.8, and 3.7%, and that of major bleeding 7.4, 9.2, and 12.9%, respectively. No bleeding was fatal. Of the 33 patients alive at 12 months, 32 (96.9%) were still on edoxaban therapy, in seven (21.2%) cancer was in progression.
Conclusion
Our study, conducted on a real world population of patients with cancer-associated VTE, confirms the results of randomized controlled clinical trials, and supports the use of edoxaban as effective and safe treatment in this context.
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