Lower Risk Of Thromboembolic Events Research Articles

Gastrointestinal Bleeding in the Setting of Anticoagulation and Antiplatelet Therapy

To review the literature on the significance, risk factors, and management of occult and gross gastrointestinal (GI) bleeding in patients on antiplatelets and/or anticoagulants. Relevant original and review articles and their bibliographies were analyzed. Estimates of risks and therapeutic outcomes were obtained from randomized trials, whereas risk factor identification was gathered from cross-control and prospective cohort studies. Antiplatelets and anticoagulants do not diminish the positive predictive value of fecal occult blood testing to find GI pathology. They increase the risk of gross GI bleeding, and predictors of hemorrhage include history of GI bleeding or ulcer disease, higher intensity of anticoagulation, combination therapy, and presence of comorbid conditions. A bleeding site is identified in most patients with peptic ulcer being the most common. In case of significant bleeding, complete or partial reversal of anticoagulation is undertaken on the basis of the balance of risks between bleeding and thromboembolic events. Early endoscopy can reveal lesions requiring endoscopic hemostasis, which can be performed in the setting of low-intensity anticoagulation. In patients with history of peptic disease or bleeding from an acid-related lesion, proton-pump inhibitors and Helicobacter pylori eradication reduce the risk of upper GI bleeding even when antiplatelet therapy is continued. Predictors of bleeding on antiplatelets and/or antithrombotics therapy have been identified, but formulation and validation of a GI bleeding index for stratification of risk in individual patients is suggested. Reversal of anticoagulation in bleeding patients is associated with a low risk of thromboembolic events and permits the performance of diagnostic and therapeutic endoscopy. Proton-pump inhibitors and H. pylori eradication reduce the risk of rebleeding in those with acid-related disease.

Characterisation of haematological profiles and low risk of thromboembolic events with bortezomib in patients with relapsed multiple myeloma

Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (< or =3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation.

Incidence of thromboembolic complications in patients with mechanical heart valves with a subtherapeutic international normalized ratio

Subtherapeutic international normalized ratios are frequently encountered in clinical practice, and patients with mechanical heart valves with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events. There are no data on thromboembolic event risk for these patients. We assessed the current practice patterns in the management of patients with mechanical heart valves with subtherapeutic international normalized ratios and assessed the risk of thromboembolic complications in this setting. The charts of patients with mechanical heart valves followed up in two anticoagulation clinics were reviewed. Patients with a history of stable, therapeutic anticoagulation but with a subtherapeutic international normalized ratio were included. Patients who underwent invasive procedures requiring temporary suspension of antithrombotic therapy were excluded. Data on use and dose of low-molecular weight heparin bridging therapy were collected. The incidence of objectively confirmed thromboembolic events within 90 days after obtaining the index international normalized ratio was assessed. Two hundred ninety-four patients with mechanical heart valves were included (mean age 63.3 years, 47.3% male). Low-molecular weight heparin was prescribed in 14 cases (4.8%). At 90 days, 1 patient had a thromboembolic complication (0.3%, 95% confidence interval 0%-1.9%). Patients with previously stable, therapeutic anticoagulation with a subtherapeutic international normalized ratio have a low risk of thromboembolic events. Withholding low-molecular weight heparin bridging therapy is a reasonable therapeutic option in these cases.

Quimioprevenção do câncer de mama

Chemoprevention is defined as the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Drugs that act as chemoprevention agents for breast cancer are divided into two major groups: drugs that prevent Estrogen Receptor (ER)-positive breast cancers [selective estrogen receptor modulators (SERM), aromatase inhibitors GnKH agonists and phytoestrogens] and drugs that prevent ER-negative breast cancers [cyclooxygenase-2 (COX-2) inhibitors, retinoids, statins, receptor tyrosine, kinase inhibitors, monoclonal antibody against HER-2 and telomerase inhibitors]. Results from the NSABP Study of Tamoxifen and Raloxifene (STAR), which compared the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk for breast cancer population, showed that Raloxifene is as effective as Tamoxifen in reducing the risk of non-invasive breast cancer (p=.83). It has a statistically significant lower risk of thromboembolic events and cataracts, however a non- statistically significant higher risk of noninvasive breast cancer. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole and exemestane, are being included in trials to evaluate their efficacy in breast cancer prevention in both case-control and cohort studies As such randomized studies to confirm this efficacy are needed. Positive results of several recent clinical trials for preventing breast cancer in high-risk populations suggest that chemoprevention is a rational and attractive strategy.

Mechanical Thrombectomy for Acute Ischemic Stroke

Mechanical thrombectomy is a promising new modality of interventional stroke treatment. The various devices differ with regard to where they apply force on the thrombus, taking a proximal approach such as aspiration devices or a distal approach such as basket-like devices. The study compares the in vivo effectiveness and thrombus-device interaction of these 2 approaches. Angiography and embolization with a radioopaque whole blood thrombus was performed in 10 swine. Mechanical thrombectomy was performed in 20 cranial vessels using a proximal aspiration device (Vasco35) and a distal basket-like device (Catch) with and without proximal balloon occlusion. Fifty-six retrieval attempts were made. The proximal device allowed fast repeated application with a low risk of thromboembolic events (3%) and vasospasm, but it had a significantly lower success rate (39.4%) in retrieving thrombotic material than the distal device (DD) (82.6%; odds ratio, 7.3; 95% CI, 2.0 to 26.4). The compaction of the thrombus during retrieval with DD increased the risk of vessel wall irritation significantly (P<0.01) and complicated retrieval into the guiding catheter. The number of embolic events was significantly higher with DD (26%; odds ratio, 11.3; 95% CI, 1.35 to 101.6) unless proximal balloon occlusion was used. The proximal and the distal approaches to mechanical thrombectomy proved to be effective at achieving recanalization of cranial vessels. The proximal device is faster in application and allowed repeated attempts with a low complication rate. The DD is more successful at removing thrombotic material, but its method of application and attendant thrombus compaction increase the risk of thromboembolic events and vasospasms.

Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes&lt;SUBTITLE&gt;The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial&lt;/SUBTITLE&gt;

Tamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis. To compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes. The National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19,747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk (mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005. Oral tamoxifen (20 mg/d) or raloxifene (60 mg/d) over 5 years. Incidence of invasive breast cancer, uterine cancer, noninvasive breast cancer, bone fractures, thromboembolic events. There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene (RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group (RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts (RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries (RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths (101 vs 96 for tamoxifen vs raloxifene) or in causes of death. Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs. clinicaltrials.gov Identifier: NCT00003906.

Vitamin D May Lower Risk of Thromboembolic Events in Prostate Cancer

Vitamin D May Lower Risk of Thromboembolic Events in Prostate Cancer

Embolismo sistémico tras reversión a ritmo sinusal del aleteo auricular persistente

The incidence of embolism in atrial flutter has been underestimated in the routine clinical practice. In this study the incidence of thromboembolic events after restoration of sinus rhythm (by catheter ablation or cardioversion) was compared in two groups of consecutive patients, with a different anticoagulation protocol. A total of 169 patients were evaluated. A first retrospective analysis of 79 non anticoagulated patients (group I). A second prospective group of 90 patients who were treated with an anticoagulation protocol (group II) similar to that for patients with atrial fibrillation. All had typical atrial flutter of at least one month's duration before the procedure. The mean age of patients in group I was 61 12 years and the mean left ventricular ejection fraction was 57 6%. Patients in group II had a mean age of 61 10 years and the mean left ventricular ejection fraction was 56 9%. No differences were observed regarding prevalence of structural cardiopathy, arterial hypertension, diabetes mellitus, left ventricular dysfunction, atrial size or atrial fibrillation between the two groups of patients. Four patients in the retrospective analysis (5%) had an embolic event associated with the procedure, compared with 0 (0%) in the group of patients treated with the anticoagulation protocol. The efficient anticoagulation was associated with a lower risk of thromboembolic events (p < 0.05). The incidence of embolic events after reversion to sinusal rhythm of persistent atrial flutter can be decreased. These patients should follow the same recommendations of anticoagulation that apply for patients with persistent atrial fibrillation that are going to be reverted to sinus rhythm.

Complementary and alternative therapies in prostate cancer

Complementary and alternative therapies are used with increasing frequency in men with prostate cancer. However, little is known about the efficacy of such therapies for this cancer. While epidemiological data support the association between intake of certain micronutrients with development of prostate cancer, there exist limited prospective data that support the chemopreventative or therapeutic value of such nutritional agents in prostate cancer. To date, one of the most studied treatments has been PC-SPES, a combination of eight herbal therapies with activity against prostate cancer. Studies in cell lines of human prostate cancer demonstrate significant dose-dependent decreases in cellular viability after exposure to extracts of this agent. Clinical studies suggested that PC-SPES could reduce prostate specific antigen levels in patients with either androgen-dependent or androgen-independent prostate cancer. Toxicity was mild, although there was a low risk of thromboembolic events with such treatment. Manufacture of PC-SPES was recently halted, after revelations that the herbal combination was contaminated with warfarin, which led to a recall by the manufacturer. Subsequent analyses also revealed the presence of diethylstilbestrol (DES) and indomethicin in some lots of PC-SPES. Available data regarding other alternative therapies are reviewed as well. Semin Oncol 29:575-584. Copyright 2002, Elsevier Science (USA). All rights reserved.

Aortic allografts for left ventricular outflow tract replacement in children.

Aortic allografts provide many advantages in children requiring left ventricular outflow tract (LVOT) reconstruction. The low risk of thromboembolic events and freedom from the requirement for anticoagulation are primary benefits. Additionally, excellent hemodynamic results are possible even in the presence of multilevel obstruction. The pulmonary autograft has become the favored approach in most pediatric centers, as the limited longevity of the aortic allograft has now become apparent. However, some children are not candidates for the pulmonary autograft. Thus, the aortic allograft remains a useful aortic valve substitute in children. Using standard aortic root replacement (ARR) or extended aortic root replacement (EARR) techniques, aortic allografts can be used in any circumstance. Young age and small size are predictive of shortened valve longevity and higher operative mortality compared with older children. Reoperation to replace a degenerated aortic allograft can be accomplished safely. Copyright 2000 by W.B. Saunders Company

Lone atrial fibrillation and anticoagulant therapy

Assessment of risk of thromboembolism and potential benefit of prophylaxis with long-term anticoagulant therapy in lone atrial fibrillation is hampered by a lack of consensus regarding definition of lone atrial fibrillation. In general, patients less than 60 years of age with normal left ventricular function and left atrial size have a low risk of thromboembolic events and are unlikely to gain any significant benefit with anticoagulants; however, patients older than 60 years with impaired left ventricular function, enlarged left atrium, and/or associated conditions such as hypertension have an increased risk of thromboembolism and would benefit from long-term anticoagulant therapy. Decisions regarding anticoagulant usage would be simplified by using a scoring system containing clinical and investigational variables.