Use of Antithrombotic Agents During Pregnancy Ginsberg, Jeffrey S.; Greer, Ian; Hirsh, Jack
Chest,
January 2001, 2001, 2001-Jan, 2001-01-00, 20010101, Letnik:
119, Številka:
1
Journal Article
Recenzirano
Anticoagulant therapy is indicated during pregnancy for the prevention and treatment of VTE; for the prevention and treatment of systemic embolism in patients with mechanical heart valves; and, often ...in combination with aspirin, for the prevention of pregnancy loss in women with APLAs or thrombophilia and previous pregnancy losses. Several questions concerning anticoagulant therapy remain unanswered. It appears that LMWH will largely replace UFH. Oral anticoagulants are fetopathic, but the true risks of the warfarin embryopathy and CNS abnormalities remain unknown. There is considerable evidence that warfarin embryopathy occurs only when oral anticoagulants are administered between the sixth week and the 12th week of gestation and that oral anticoagulants may not be fetopathic when administered in the first 6 weeks of gestation. Oral anticoagulant therapy should be avoided in the weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. The safety of aspirin during the first trimester of pregnancy is still a subject of debate. There is a concern about the efficacy of UFH in the prevention of arterial embolism in pregnant women with mechanical heart valves. Finally, the optimum management of pregnant women with thrombophilia (and prior pregnancy loss and/or prior VTE) is unknown, but trials of anticoagulant therapy are ongoing. Because it is safe for the fetus, LMWH (or UFH) is the anticoagulant of choice during pregnancy for situations in which its efficacy is established. There is some doubt that heparin is effective for the prevention of systemic embolism in patients with mechanical heart valves. Low doses of heparin or poorly controlled heparin therapy are not effective in preventing systemic embolism in patients with mechanical heart valves.
Background/objectives: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including ...development of the post‐thrombotic syndrome (PTS). Patients/methods: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self‐completed. Generic QOL was measured using the Short‐Form Health Survey‐36 (SF‐36) questionnaire. Venous disease‐specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)‐QOL/Sym questionnaire. The change in QOL scores over a 2‐year follow‐up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. Results: Among the 387 patients recruited, the average age was 56 years, two‐thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow‐up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P‐values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES‐QOL and VEINES‐Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2‐year SF‐36 PCS scores. PTS alone independently predicted 2‐year VEINES‐QOL (P < 0.0001) and VEINES‐Sym (P < 0.0001) scores. Conclusions: Development of PTS is the principal determinant of health‐related QOL 2 years after DVT. Our study provides prognostic information on patient‐reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.
Summary
Background
Clinical situations occur where expedient assessment of the anticoagulant activity of the direct factor Xa (FXa) inhibitors is required. Although quantitative anti‐FXa (FXa) assays ...can be used to measure plasma levels of apixaban or rivaroxaban, turnaround is often slow and many laboratories do not perform these assays.
Objective
We compared the in vitro effects of apixaban and rivaroxaban on two readily available laboratory tests, the prothrombin time (PT) and activated partial thromboplastin time (APTT), performed with different reagents. We aimed to identify the most sensitive reagents.
Methods
Rivaroxaban or apixaban was added to human plasma at a range of concentrations covering expected peak and trough levels, and concentrations were confirmed using calibrated anti‐FXa assays. Samples were assayed with six PT and seven APTT reagents using different coagulometers.
Results and Conclusions
TriniCLOT PT Excel S was the only reagent to demonstrate sensitivity to apixaban. All of the PT reagents were sensitive to rivaroxaban with TriniCLOT PT Excel S and HemosIL HS PLUS being the most sensitive. Sensitivity to rivaroxaban varied among APTT reagents; four reagents exhibited the greatest responsiveness, and of these, Actin FSL was the most responsive. Commonly used coagulation tests may be useful for assessing the anticoagulant effect of rivaroxaban but not of apixaban. The reason for the different effects of apixaban and rivaroxaban on the PT and APTT is unknown.
Background: Few studies have evaluated the long‐term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate ...identification of incident cases of DVT and DVT‐related health outcomes of interest, such as post‐thrombotic syndrome (PTS). Objectives: To prospectively quantify medical and non‐medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs. Methods: Three hundred and fifty‐five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient‐completed cost diaries, nurse‐completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ). Results: The rate of DVT‐related hospitalization was 3.5 per 100 patient‐years (95% confidence interval CI 2.2–4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professional visits. The average cost of DVT was $5180 (95% CI $4344–6017) in Canadian dollars, with 51.6% of costs being attributable to non‐medical resource use. Multivariate analysis identified four independent predictors of costs: concomitant pulmonary embolism (relative increase in cost RIC 3.16; 95% CI 2.18–4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28–2.13), development of PTS during follow‐up (RIC 1.35; 95% CI 1.05–1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33–2.40). Conclusions: The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.
Summary
Background
In clinical practice, physicians are given the choice of selecting one of two dabigatran doses based on patient characteristics, with the lower dose typically used in patients at a ...higher risk of bleeding.
Objectives
The objectives of the study were to (i) estimate the inter‐ and intra‐patient variability in dabigatran levels with 110 mg (DE110) and 150 mg (DE150) doses, (ii) examine the effect of physicians’ dose selection on levels in DE110 and DE150 subgroups, and (iii) explore whether a single trough measurement identifies patients with extreme levels on subsequent visits.
Methods
In this prospective observational study of 100 patients with atrial fibrillation (AF), peak and trough levels of dabigatran were measured with the Hemoclot® assay at baseline and every 2 months thereafter (maximum four visits).
Results
Inter‐patient variability in dabigatran levels (geometric coefficient of variation gCV, 51–64%) was greater than intra‐patient variability (gCV, 32–40%). Similar medians and distributions of levels were observed in DE110 and DE150 subgroups. Patients receiving DE110 were older, had lower renal function and weighed less than those receiving DE150. Up to 40% of patients whose trough levels were in the upper extremes, and up to 80% of patients whose trough levels were in the lower extremes at baseline, showed subsequent levels that fell in the middle quartiles.
Conclusions
Our data support the practice of selecting the dabigatran dose based upon clinical characteristics because it results in similar levels of drug exposure in patients given DE110 or DE150. They do not support the concept that a single Hemoclot® measurement reliably identifies patients with consistently high or low values.
Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, ...there are no prospective data to support this approach to thromboprophylaxis.
We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin.
A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8).
High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.
Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer's disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are ...epigenetic "readers" that may distort normal gene expression and contribute to chronic disorders.
To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE).
The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized to apabetalone or placebo in the cognition sub-study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score≥26 (normal performance), MoCA score 25-22 (mild cognitive impairment), and MoCA score≤21 (dementia). Exposure to apabetalone was equivalent in the treatment groups in each MoCA-defined group.
Apabetalone was associated with an increased total MoCA score in participants with baseline MoCA score of≤21 (p = 0.02). There was no significant difference in change from baseline in the treatment groups with higher MoCA scores. In the cognition study, more patients randomized to apabetalone discontinued study drug for adverse effects (11.3% versus 7.9%).
In this randomized controlled study, apabetalone was associated with improved cognition as measured by MoCA scores in those with baseline scores of 21 or less. BET protein inhibitors warrant further investigation for late life cognitive disorders.
We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and ...determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was <2.0, moderate of the score was 2.0 to 6.0 and high if the score was over 6.0. Pulmonary embolism unlikely was assigned to patients with scores < or =4.0 and PE likely if the score was >4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.
Essentials
Coronary artery bypass graft (CABG) failure is associated with myocardial infarction and death.
We tested whether more frequent dosing improves aspirin (ASA) response following CABG ...surgery.
Twice‐daily compared with once‐daily dosing reduces ASA hyporesponsiveness after CABG surgery.
The efficacy of twice‐daily ASA needs to be tested in a trial powered for clinical outcomes.
Summary
Background
Acetyl‐salicylic acid (ASA) hyporesponsiveness occurs transiently after coronary artery bypass graft (CABG) surgery and may compromise the effectiveness of ASA in reducing thrombotic graft failure. A reduced response to ASA 81 mg once‐daily after CABG surgery is overcome by four times daily ASA dosing.
Objectives
To determine whether ASA 325 mg once‐daily or 162 mg twice‐daily overcomes a reduced response to ASA 81 mg once‐daily after CABG surgery.
Methods
Adults undergoing CABG surgery were randomized to ASA 81 mg once‐daily, 325 mg once‐daily or 162 mg twice‐daily. The primary outcome was median serum thromboxane B2 (TXB2) level on postoperative day 4. We pooled the results with those of our earlier study to obtain better estimates of the effect of ASA 325 mg once‐daily or in divided doses over 24 h.
Results
We randomized 68 patients undergoing CABG surgery. On postoperative day 4, patients randomized to receive ASA 81 mg once‐daily had a median day 4 TXB2 level of 4.2 ng mL−1 (Q1, Q3: 1.5, 7.5 ng mL−1), which was higher than in those randomized to ASA 162 mg twice‐daily (1.1 ng mL−1; Q1, Q3: 0.7, 2.7 ng mL−1) and similar to those randomized to ASA 325 mg once‐daily (1.9 ng mL−1; Q1, Q3: 0.9, 4.7 ng mL−1). Pooled data showed that the median TXB2 level on day 4 in groups receiving ASA 162 mg twice‐daily or 81 mg four times daily was 1.1 ng mL−1 compared with 2.2 ng mL−1 in those receiving ASA 325 mg once‐daily.
Conclusions
Multiple daily dosing of ASA is more effective than ASA 81 mg once‐daily or 325 mg once‐daily at suppressing serum TXB2 formation after CABG surgery. A twice‐daily treatment regimen needs to be tested in a clinical outcome study.
Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing ...venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.
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