Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in ...fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding. The absolute benefits of direct oral anticoagulants over vitamin K antagonists are modest; however, guidelines recommend them in preference to vitamin K antagonists for most indications because of their ease of use and superior safety. The greatest benefits of direct oral anticoagulants are likely to be in patients who were previously deemed unsuitable for vitamin K antagonist therapy. The emergence of generic preparations is expected to further increase the uptake of direct oral anticoagulants, particularly in countries where they are currently not widely used because of cost. Direct oral anticoagulants are contraindicated in patients with mechanical heart valves and should be used with caution or avoided in patients with advanced kidney or liver disease. In this Therapeutics paper, we review the pharmacology of direct oral anticoagulants, summarise the evidence that led to their approval and incorporation into treatment guidelines, and explore key unresolved issues. We also briefly discuss future perspectives for the development of oral anticoagulants.
Objectives The objective of this study was to determine whether colchicine 0.5 mg/day can reduce the risk of cardiovascular events in patients with clinically stable coronary disease. Background The ...presence of activated neutrophils in culprit atherosclerotic plaques of patients with unstable coronary disease raises the possibility that inhibition of neutrophil function with colchicine may reduce the risk of plaque instability and thereby improve clinical outcomes in patients with stable coronary disease. Methods In a clinical trial with a prospective, randomized, observer-blinded endpoint design, 532 patients with stable coronary disease receiving aspirin and/or clopidogrel (93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years. The primary outcome was the composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. The primary analysis was by intention-to-treat. Results The primary outcome occurred in 15 of 282 patients (5.3%) who received colchicine and 40 of 250 patients (16.0%) assigned no colchicine (hazard ratio: 0.33; 95% confidence interval CI 0.18 to 0.59; p < 0.001; number needed to treat: 11). In a pre-specified secondary on-treatment analysis that excluded 32 patients (11%) assigned to colchicine who withdrew within 30 days due to intestinal intolerance and a further 7 patients (2%) who did not start treatment, the primary outcome occurred in 4.5% versus 16.0% (hazard ratio: 0.29; 95% CI: 0.15 to 0.56; p < 0.001). Conclusions Colchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease.
A Test in Context: D-Dimer Weitz, Jeffrey I.; Fredenburgh, James C.; Eikelboom, John W.
Journal of the American College of Cardiology,
11/2017, Letnik:
70, Številka:
19
Journal Article
Recenzirano
Odprti dostop
D-dimer is a soluble fibrin degradation product that results from ordered breakdown of thrombi by the fibrinolytic system. Numerous studies have shown that D-dimer serves as a valuable marker of ...activation of coagulation and fibrinolysis. Consequently, D-dimer has been extensively investigated for the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and as an aid in the identification of medical patients at high risk for VTE. Thus, quantification of D-dimer levels serves an important role in guiding therapy. This review: 1) describes how D-dimer is generated; 2) reviews the assays used for its detection; and 3) discusses the role of D-dimer determination in these various conditions.
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In a pragmatic trial, more than 30,000 patients requiring blood transfusion were randomly assigned to receive blood after short-term storage or long-term storage. In-hospital mortality did not differ ...significantly between the two groups.
Red-cell transfusion is one of the most common medical interventions.
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Blood is stored for up to 42 days before transfusion. Biochemical, structural, and functional changes during storage may reduce oxygen delivery to tissues, and the release of extracellular vesicles and cell-free DNA during storage may cause a hypercoagulable state.
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Observational studies have suggested that prolonged blood storage is associated with an increased risk of cardiovascular events.
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Randomized, controlled trials have not shown harm in transfusing red-cell units with a longer duration versus a shorter duration of storage. However, most of these trials have been restricted to high-risk populations and have . . .
Factor XI inhibitors: cardiovascular perspectives De Caterina, Raffaele; Prisco, Domenico; Eikelboom, John W
European heart journal,
2023-Jan-21, 2023-01-21, 20230121, Letnik:
44, Številka:
4
Journal Article
Recenzirano
Anticoagulants are the cornerstone for prevention and treatment of thrombosis but are not completely effective, and concerns about the risk of bleeding continue to limit their uptake. Animal studies ...and experience from patients with genetic coagulation factor XI deficiency suggesting that this factor is more important for thrombosis than for haemostasis raises the potential for drugs that target factor XI to provide safer anticoagulation. Multiple factor XI inhibitors are currently under evaluation in clinical trials, including parenterally administered antisense oligonucleotides, monoclonal antibodies, and orally active small-molecule inhibitors. Promising results of phase 2 trials in patients undergoing major orthopaedic surgery, and in those with end-stage kidney disease, atrial fibrillation and acute coronary syndromes have led to large phase 3 trials that are currently ongoing. We here review premises for the use of these agents, results so far accrued, ongoing studies, and perspectives for future patient care.
Summary Background The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and ...validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation. Methods We developed and internally validated a new biomarker-based risk score for major bleeding in 14 537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov , numbers NCT00412984 and NCT00262600 , respectively. Findings The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers GDF-15, cTnT-hs, and haemoglobin, and clinical history previous bleeding) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0·68 95% CI 0·66–0·70 vs 0·61 0·59–0·63 vs 0·65 0·62–0·67, respectively; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0·71 95% CI 0·68–0·73 vs 0·62 0·59–0·64 for HAS-BLED vs 0·68 0·65–0·70 for ORBIT; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores. Interpretation The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation. Funding BMS, Pfizer, Boehringer Ingelheim, Roche Diagnostics.
Low-Dose Aspirin and Recurrent Thromboembolism
Results from the ASPIRE trial add evidence supporting the use of low-dose daily aspirin for preventing recurrent venous thromboembolism in patients who ...have had an initial unprovoked clotting episode.
Patients who have had a first episode of unprovoked venous thromboembolism are at high risk for recurrence after anticoagulant therapy is discontinued.
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Long-term treatment with a vitamin K antagonist is very effective in preventing a recurrence of venous thromboembolism while treatment continues
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but has not been shown to improve survival, is associated with a substantially increased risk of bleeding, and is inconvenient for patients.
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Consequently, many patients who have had a first episode of unprovoked venous thromboembolism discontinue anticoagulant therapy after 3 to 6 months despite recommendations to prolong therapy.
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Low-dose aspirin is a simple, inexpensive, and widely . . .
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