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NEJM Journal Watch: Summaries of and commentary on original medical and scientific articles from key medical journals

Rivaroxaban (Xarelto) and apixaban (Eliquis) are the most commonly prescribed direct-acting oral anticoagulants (DOACs) in the U.S., but no head-to-head comparisons are available to guide physicians' choices between these drugs. In this study, researchers used a large U.S. claims database to compare the effectiveness and safety of rivaroxaban and apixaban in patients with newly diagnosed venous thromboembolism (VTE). About 3000 apixaban users were compared with about 12,000 propensity-score-matched rivaroxaban users. During average follow-up of about 3 months, recurrent VTE occurred significantly less often in apixaban users than in rivaroxaban users (3 vs. 7 events per 100 person-years). Major bleeding also occurred significantly less often with apixaban (3 vs. 6 events per 100 person-years). These findings were consistent across various subgroups.

Can Anticoagulants Prevent Alzheimer's?

After receiving dabigatran for 1 year, the mice had no memory loss, and there was no reduction in cerebral circulation. Dabigatran also reduced typical AD symptoms, including cerebral inflammation, blood vessel injury, and amyloid protein plaques.

Can Anticoagulants Prevent Alzheimer's?

In the new study, long-term anticoagulation therapy with dabigatran (Pradaxa, Boehringer Ingelheim) inhibited thrombin and abnormal deposition of fibrin in a mouse model of AD. After receiving dabigatran for 1 year, the mice had no memory loss, and there was no reduction in cerebral circulation. Dabigatran also reduced typical AD symptoms, including cerebral inflammation, blood vessel injury, and amyloid protein plaques.

Apixaban: Evaluation of the Inclusion of Studies Identified by the FDA as Having Falsified Data in the Results of Meta-analyses: The Example of the Apixaban Trials | Research, Methods, Statistics | JAMA Internal Medicine | JAMA Network

In our reanalysis of the 22 meta-analyses, we found that 10 (46%) yielded results that would change the initial meta-analysis findings. Each affected meta-analysis had a median of 9.5 publications (range, 2-17), and the median meta-analysis publication InCite journal impact factor was 5.830 (range, 3.154-17.202). The median weight of publications with falsified data was 55.7% (range, 13.1%-99.6%). From our reanalysis of the 22 meta-analyses, we found that 32 of 99 analyses (32%) yielded results that would change the conclusions of the initial analysis (Table). Of the 32 affected estimates, 31 (97%) no longer favored apixaban for the prevention of serious medical issues, and 1 (3%) favored the control.

Blood clot discovery could pave way for treatment of blood diseases -- ScienceDaily

Amongst other unwanted effects, free radicals play a role in the build-up of blood clots, which in turn are considered a key driver in the a development of a range of conditions, including heart disease, stroke, dementia, and inflammation-related conditions such as arthritis. The new technique is outlined in research published in Haematologica. The technique combines electron paramagnetic resonance, a cutting-edge method for detecting free radicals, with blood cell aggregometry, an established technique for measuring blood clotting. The team has successfully used the technique in mice and in human cells. They aim to better understand how blood cells function, which will help to develop new drugs against blood clotting diseases or to test the risk of clotting diseases in patients.

Platelet 'decoys' outsmart both clots and cancer: Deactivated platelets offer a potential drug-free, reversible antiplatelet therapy -- ScienceDaily

Now, a team of researchers at the Wyss Institute at Harvard University and several collaborating institutions has created a drug-free, reversible antiplatelet therapy that employs deactivated "decoy" platelets that could reduce the risk of blood clots and potentially prevent cancer metastasis as well. The research is reported in Science Translational Medicine. "The reversibility and immediate onset of action are major advantages of our platelet decoys, and we envision them to be useful in hospital-based situations such as preventing clotting in high-risk patients just before they undergo surgery, or when given alongside chemotherapy to prevent existing tumors from spreading," said first author Anne-Laure Papa, Ph.D., who was a postdoctoral fellow at the Wyss Institute working with the Institute's Founding Director, Donald Ingber, M.D., Ph.D. when the research was carried out and is now an Assistant Professor at George Washington University. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences.

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism | NEJM

Efficacy Table 2. Prespecified Efficacy Outcomes. A primary efficacy outcome event occurred in 17 of 1107 patients (1.5%) who were receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) who were receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) who were receiving aspirin. Fatal venous thromboembolism occurred in 2 patients (0.2%) who were receiving 20 mg of rivaroxaban, in no patients who were receiving 10 mg of rivaroxaban, and in 2 patients (0.2%) who were receiving aspirin (Table 2). Both rivaroxaban doses were superior to aspirin with respect to the primary efficacy outcome (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). The hazard ratio for the comparison between the 20-mg and 10-mg rivaroxaban regimens was 1.34 (95% CI, 0.65 to 2.75; P=0.42). Similar results were found for the other efficacy outcomes (Table 2, and Table S4 in the Supplementary Appendix). Table 3. Rates of Recurrent Venous Thromboembolism and Major Bleeding, According to Risk Profile and Duration of Anticoagulation before Randomization. Figure 2. Kaplan–Meier Rates of Recurrent Fatal or Nonfatal Venous Thromboembolism and Major Bleeding. With aspirin, the rate of recurrent venous thromboembolism was 3.6% among the patients in whom the index event was provoked (i.e., associated with a known event, such as surgery or hospital admission) and 5.6% among those in whom the index event was unprovoked (i.e., idiopathic) (Table 3). Rates of recurrence in patients whose index events were provoked or unprovoked were lower in both the 20-mg rivaroxaban group (1.4% and 1.8%, respectively) and the 10-mg rivaroxaban group (0.9% and 1.5%, respectively) than in the aspirin group.

Three Genes for Blood Clots - 23andMe Blog

Fracturing your hip or leg, having hip or knee replacement surgery, being immobilized like on a long flight, being pregnant, smoking, and taking oral birth control pills all increase risk for VTE to varying degrees. Genetics also plays a role and a new study by lead author John Heit from the Mayo Clinic suggests that variants of just three genes – F5, F2, and ABO – account for nearly all the possible genetic risk in people with European ancestry. These results imply that researchers are unlikely to discover new genetic factors that significantly impact VTE risk in the general population. Two of the three major genes have especially large impacts on risk for VTE. The F5 gene encodes the factor V clotting factor, a protein that causes blood cells to stick together.

Treatment Duration for Pulmonary Embolism | Pulmonary Medicine | JAMA | JAMA Network

The study compared the effects of giving blood-thinning medication for 6 months compared with 2 years. The study looked at how often people in each group had (1) another blood clot and (2) major bleeding as a side effect. The results showed a significantly lower risk of having another blood clot in the group that received the treatment for longer (2 years), without a major increase in bleeding risk.

Stopping anticoagulant therapy after an unprovoked venous thromboembolism

Importantly, the study by Rodger and colleagues confirms that patients who had a first unprovoked venous thromboembolism have a high overall risk of recurrence after stopping anticoagulant (about 11% at 1 year and about 17% at 2 years). In addition, they found no association between the presence of residual thrombosis of the deep veins on ultrasound and risk of recurrence, which argues against using this finding to determine the duration of treatment.

Stopping anticoagulant therapy after an unprovoked venous thromboembolism

Between these 2 extremes lie patients who have had a venous thromboembolism associated with a minor reversible risk factor (e.g., estrogen therapy or soft-tissue leg injury) and those who have had an “unprovoked” venous thromboembolism (also referred to as “idiopathic” or “spontaneous”).3 For patients with a minor reversible risk factor, the risk of recurrence is about 5% in the first year after stopping anticoagulant therapy.3 This is considered low enough to justify stopping anticoagulant therapy at the end of 3 months.1 However, an unprovoked proximal deep venous thrombosis or pulmonary embolism has a higher risk of recurrence (about 10% in the first year after stopping therapy). Continuing anticoagulant therapy beyond 3 months confers a greater than 90% risk reduction for preventing recurrence among these patients; however, if anticoagulants are subsequently stopped after 6 or 12 months of treatment, the risk of recurrence appears to be the same as if anticoagulants had been stopped after 3 months.1

Aspirin alone a good clot buster after knee surgery -- ScienceDaily

Over three months, just 1.16 percent of aspirin patients developed a serious blood clot. That was true for 1.42 percent of anticoagulant patients, according to the Michigan study. This was not statistically different. So, neither drug appeared better than the other -- but aspirin has some obvious advantages. "Aspirin is easy to take and much less expensive," Hallstrom says. "Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive." The reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450; heparin is estimated at $450 to $890. Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, Hallstrom says.