The impact of adding aspirin to warfarin without an apparent indication: An exploration of patients anticoagulated for atrial fibrillation or venous thromboembolic disease.

Introduction: Warfarin and aspirin (ASA) are widely used to prevent or treat thromboembolic and atherosclerotic diseases. The most common indications for warfarin use are stroke prevention in atrial fibrillation (AF) and for the treatment of venous thromboembolic disease (VTE). When patients are started on warfarin, many are already taking ASA or they are subsequently placed on ASA due to other co-morbidities. There are limited indications for the combination of warfarin plus ASA, including mechanical heart valves, after percutaneous coronary intervention (PCI), or after acute coronary syndromes. Evidence suggests combination warfarin-ASA may offer no benefit, but place patients at increased bleeding risk outside of these indications. We sought to assess the patient characteristics and outcomes of patients on warfarin for AF or VTE, comparing those who were on concurrent ASA without a strong indication (myocardial infarction [MI] within 6 months, mechanical heart valve or PCI) to those not on ASA. We hypothesized that combination therapy (warfarin-ASA) would result in increased bleeding rates with similar rates of MI, recurrent VTE, stroke, or death. Methods: We conducted a retrospective cohort study of adult patients, initiated on warfarin for AF or VTE between January 2009 and June 2017. Patients were recruited through the Michigan Anticoagulation Quality Improvement Initiative, a collaborative of six outpatient anticoagulation clinics throughout the state of Michigan. Patients with less than three months of follow-up, a MI within six months, and/or history of valve replacement were excluded. Patients were analyzed based on their aspirin use at the time of study enrollment. A HAS-BLED score, modified to exclude aspirin use, and a Charlson Co-morbidity Index was calculated for each patient at enrollment. Analyses were performed using Student\u27s t-tests, Wilcoxon Rank-sum tests, chi-square tests and Fisher\u27s exact tests when appropriate. Survival and Poisson regression analyses were used to evaluate the effect of ASA use on various outcomes. Results: A total of 6,572 patients met the inclusion criteria, with a mean duration of follow-up of 21.2 months; 38% were on warfarin-ASA compared to 62% on warfarin monotherapy. Patients on warfarin-ASA were older (mean 70.2±12.7 vs. 63.7±16.5, p\u3c0.001), more often male (56.7% vs. 47.3%, p\u3c0.001), and were more likely anticoagulated for AF (66.3% vs. 42.3%, p\u3c0.001). Warfarin-ASA patients were more likely to have cardiovascular risk factors (diabetes mellitus, tobacco use, or hypertension), a history of stroke, heart failure, or a history of coronary artery disease (CAD). Patients on warfarin-ASA had a higher HAS-BLED score (mean 2.4±1.2 vs. 1.8±1.2, p\u3c0.001), and Charlson Co-morbidity Index (mean 4.8±2.0 vs. 3.6±2.1, p\u3c0.001). Patients treated with warfarin-ASA vs. warfarin alone experienced less DVTs (0.7/100 patient years [pt-yr] vs. 1.3/100-pt-yr, p=0.002) and PE (0.1/100-pt-yr vs. 0.4/100-pt-yr, p=0.002), but had a higher rate of ischemic/embolic strokes (0.7/100-pt-yr vs. 0.4/100-pt-yr, p=0.02). Emergency department visits and hospitalizations for thromboembolic events were similar. Patients treated with warfarin-ASA vs. warfarin alone had a higher 1-year probability of having a major bleeding event (6.1% vs. 3.2%, p\u3c0.001) or non-major bleeding event (22.9% vs. 18.7%, p=0.004). Warfarin-ASA treated patients had a higher rate of hospitalizations for bleeding (8.4/100-pt-yr vs. 5.7/100-pt-yr, p\u3c0.001), blood transfusions (5.2/100-pt-yr vs. 4.1/100-pt-yr, p=0.009) and all-cause mortality relative to warfarin alone (4.1/100-pt-yr vs. 3.1/100-pt-yr, p=0.005). Kaplan- Meier curves for any clotting event, all bleeding events, major bleeding events, and death are shown (figure 1). A sensitivity analysis was performed that further excluded any history of MI, CAD, PCI, peripheral arterial disease, or coronary artery bypass grafting, and showed similar results. Conclusion: Over one-third of patients in an unselected practice-based setting are treated with warfarin-ASA for AF and/or VTE without a clear indication. Compared to warfarin monotherapy, this was associated with minimally increased protection against VTE but with a significant increase in bleeding and perhaps mortality. Further research is needed to better stratify who should receive aspirin while on warfarin

Sociodemographic factors in patients continuing warfarin vs those transitioning to direct oral anticoagulants.

Clinical factors and patient preferences are important for selecting oral anticoagulants for venous thromboembolism (VTE) and atrial fibrillation (AF). The relative association of sociodemographic factors with anticoagulant use is unknown. We evaluated a prospective cohort to compare sociodemographic variables in patients who continued on warfarin for AF or VTE to those who transitioned to 1 of the direct oral anticoagulants (DOACs). Adult patients, newly started on warfarin, were enrolled through 6 anticoagulation clinics across Michigan. Of 8468 patients, 53.3% had AF, 45.6% had VTE, and 1.1% had both. Of these, 696 (8.2%) switched from warfarin to a DOAC. There were no significant differences between switchers and nonswitchers for percentage of time with a therapeutic international normalized ratio on warfarin, urban-rural residence status, or health insurance. Switchers were more often white (83.3% vs 77.7%; P \u3c .001), partnered (67.3% vs 59.2%; P \u3c .001), or resided in a zip code with a higher median household income (P \u3c .001). The results show that sociodemographic factors, such as race, partnered status, and income are associated with a patient\u27s likelihood of switching to a DOAC vs remaining on warfarin therapy. Although clinical factors predominate, the reason for, and impact of, these observed variations in care requires further investigation

Association of Adding Aspirin to Warfarin Therapy Without an Apparent Indication With Bleeding and Other Adverse Events

Importance: It is not clear how often patients receive aspirin (acetylsalicylic acid) while receiving oral anticoagulation with warfarin sodium without a clear therapeutic indication for aspirin, such as a mechanical heart valve replacement, recent percutaneous coronary intervention, or acute coronary syndrome. The clinical outcomes of such patients treated with warfarin and aspirin therapy compared with warfarin monotherapy are not well defined to date. Objective: To evaluate the frequency and outcomes of adding aspirin to warfarin for patients without a clear therapeutic indication for combination therapy. Design, Setting, and Participants: A registry-based cohort study of adults enrolled at 6 anticoagulation clinics in Michigan (January 1, 2010, to December 31, 2017) who were receiving warfarin therapy for atrial fibrillation or venous thromboembolism without documentation of a recent myocardial infarction or history of valve replacement. Exposure: Aspirin use without therapeutic indication. Main Outcomes and Measures: Rates of any bleeding, major bleeding events, emergency department visits, hospitalizations, and thrombotic events at 1, 2, and 3 years. Results: Of the study cohort of 6539 patients (3326 men [50.9%]; mean [SD] age, 66.1 [15.5] years), 2453 patients (37.5%) without a clear therapeutic indication for aspirin were receiving combination warfarin and aspirin therapy. Data from 2 propensity score-matched cohorts of 1844 patients were analyzed (warfarin and aspirin vs warfarin only). At 1 year, patients receiving combination warfarin and aspirin compared with those receiving warfarin only had higher rates of overall bleeding (cumulative incidence, 26.0%; 95% CI, 23.8%-28.3% vs 20.3%; 95% CI, 18.3%-22.3%; P \u3c .001), major bleeding (5.7%; 95% CI, 4.6%-7.1% vs 3.3%; 95% CI, 2.4%-4.3%; P \u3c .001), emergency department visits for bleeding (13.3%; 95% CI, 11.6%-15.1% vs 9.8%; 95% CI, 8.4%-11.4%; P = .001), and hospitalizations for bleeding (8.1%; 6.8%-9.6% vs 5.2%; 4.1%-6.4%; P = .001). Rates of thrombosis were similar, with a 1-year cumulative incidence of 2.3% (95% CI, 1.6%-3.1%) for those receiving combination warfarin and aspirin therapy compared with 2.7% (95% CI, 2.0%-3.6%) for those receiving warfarin alone (P = .40). Similar findings persisted during 3 years of follow-up as well as in sensitivity analyses. Conclusions and Relevance: Compared with warfarin monotherapy, receipt of combination warfarin and aspirin therapy was associated with increased bleeding and similar observed rates of thrombosis. Further research is needed to better stratify which patients may benefit from aspirin while anticoagulated with warfarin for atrial fibrillation or venous thromboembolism; clinicians should be judicious in selecting patients for combination therapy

Permanent genetic resources added to molecular ecology resources database 1 May 2009–31 July 2009

This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis ( Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle, Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species

Predicting coral recruitment in Palau's complex reef archipelago

Reproduction and recruitment are key processes that replenish marine populations. Here we use the Palau archipelago, in the western Pacific Ocean, as a case study to examine scales of connectivity and to determine whether an oceanographic model, incorporating the complex reef architecture, is a useful predictor of coral recruitment. We tested the hypothesis that the reefs with the highest retention also had the highest densities of juvenile coral density from 80 field sites. Field comparisons showed a significant correlation between the densities of juvenile Acropora colonies and total larval recruitment derived from the model (i.e., calculated as the sum of the densities of larvae that self-seeded and recruited from the other reefs in the archipelago). Long-distance larval imports may be too infrequent to sustain coral populations, but are critical for recovery in times of extreme local stress