Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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DOAC Reduces Stroke Risk After Ventricular Ablation
DOACs eliminated stroke with a 6.5% rate with aspirin through 30 days as seen in the STROKE-VT trial. TIAs occurred in 4.9% of the DOAC group versus 18% of those on aspirin. There was also a decrease in subclinical brain lesions in the DOAC group, while bleeding complications and in hospital mortality were similar between groups. These results could contribute to DOACs becoming the standard of care for ventricular tachycardia and premature ventricular contractions left-sided ablations.
The multicenter trial included 246 patients being treated with LV catheter ablation mainly for VT from ischemic or nonischemic cardiomyopathy; 25% were treated for premature ventricular contractions. Idiopathic ventricular arrhythmias were included in the study population. Patients were randomized to 81mg of aspirin daily without a loading dose or for those on an antiplatelet therapy returned to their pre-existing regimen. Aspirin was the strongest predictor for both CVA accidents and asymptomatic embolic lesions.
Low-Dose Aspirin Linked to Lower Dementia Risk in Some Individuals
In patients with coronary heart disease, low dose acetylsalicylic acid (LDASA) may have some protective benefit against cognitive decline if started prior to the onset of symptoms of dementia. Pathological symptoms of dementia may occur up to 2 decades prior to symptom onset therefore waiting until 65 or older may be too late.
The results were compiled from two databases: UK Biobank and ESTHER with a 10 year follow up, adjusting for confounders and balancing the distribution of measured baseline covariates to be similar between both users of LDASA and non-users. The cohorts used were combined into a meta-analysis. The ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older. The strongest association was found in subjects with coronary heart disease. Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer's disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48).
While results are promising, the only way to obtain a true understanding of causation would be to conduct a clinical trial with 10 years of follow up.
Disparities Seen in Use of Standard of Care Blood Thinners for Atrial Fibrillation
Data from 111,666 patients within the VA system, it was noted that when compared to white patients, black patients were 26% less likely to be treated with standard of care blood thinners. Hispanic patients were 21% less likely and Native American/Alaska Native 25% less likely to receive DOACs after a diagnosis of AF. These groups are less likely to get the newer class of medication for stroke prevention.
The 111, 666 patients were from the Race, Ethnicity and Anticoagulant Choice in Atrial Fibrillation (REACH-AF), a national, retrospective cohort of patients enrolled in the VA system with incident, nonvalvular atrial fibrillation from 2010 through 2018.
The subject included 98.0% men, 2.0% women and 85.5% were white, with a mean age of 72.9 years. Other racial/ethnic groups in decreasing frequency were Black (9.2%), Hispanic (3.7%), Asian (1.6%), and AI/AN (0.5%). The majority of patients had a moderate (62.9%) or high (24.3%) stroke risk. A total of 69,590 patients (62.3%) initiated any anticoagulant therapy within 90 days of an index atrial fibrillation diagnosis, with initiation rates lowest in Asian (52.2%) and Black (60.3%) patients, and highest in white patients (62.7%).
Minority patients may be less likely to initiate therapy for several reasons including distrust of the medical system, however there is racial and ethnic disparities with regard to which anticoagulant is prescribed.
Direct Oral Anticoagulants: Competition Brought No Cost Relief
According to Medicare Part D prescription plan, the spending of OACs, have risen almost 1600% since 2011, while the users have increased by 95%. By 2019, there were four DOACs on the market spending was $7.38 billion with an increase of 1577%. Those using DOACs went from 2.68 million to 5.24 million. DOACs offer the benefits of decreased drug-drug interactions and improved persistence.
In 2011 0.2 million Medicare beneficiaries took DOACs compared with 3.5 million in 2019. The number of warfarin users dropped from 2.48 million to 1.74 million. The cost to treat one beneficiary with atrial fibrillation increased by 9.3% each year for apixaban (a DOAC that was the most popular oral anticoagulant in 2019), decreased 27.6% per year for generic warfarin, and increased 9.5% per year for rivaroxaban.
Apixaban Has Benefits Over Other DOACs in Frail Adults With Atrial Fibrillation
Apixaban has been associated with lower rates of adverse clinical outcomes versus warfarin in all levels of frail adults: non-frail, pre-frail, and frail. Dabigatran and rivaroxaban were associated with lower adverse events only among non-frail adults. Findings are based on a propensity score matched analysis of hundreds of thousands of Medicare beneficiaries with AF who started warfarin or a DOAC.
Apixaban was associated with a 32% reduction in the risk of the composite outcome of death, ischemic stroke, or major bleeding when compared with warfarin and reductions of 27-39% across frailty levels. There was only a 12-19% reduction in non-frail patients found with warfarin, dabigatran and rivaroxaban. Apixaban demonstrated a large reduction in major bleeding due to older adults having decreased renal function, resulting in higher concentrations of renally cleared DOACs.
Five Risk Factors May Predict Thrombus on LAA Occlusion Implants
There have been five independent predictors of device related thrombus (DRT) identified in the LAAO-DRT registry. They include the presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, and implantation depth greater than 10mm from the pulmonary ridge and the presence of nonparoxysmal atrial fibrillation.
LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AF. Predicting DRT is a priority for the LAAO field, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.
The odds ratios (OR) for DRT associated with the five identified risk factors were:
- 17.50 (95% CI, 3.39 - 90.45) for hypercoagulability disorder
- 13.45 (95% CI, 1.46 - 123.52) for pericardial effusion
- 4.02 (95% CI, 1.22 - 13.25) for renal insufficiency
- 2.41 (95% CI, 1.57 - 3.69) for implantation depth >10 mm
- 1.90 (95% CI, 1.22 - 2.97) for nonparoxysmal AF
The risk for a composite of death, ischemic stroke and systemic embolization was twofold higher in the DRT cohort than the control group while the risk of bleeding and ICH were similar in both groups. The focus of LAAO implantation should remain on optimal patient selection for the purpose of achieving safe and successful outcomes.
COVID-19 an Independent Driver for Heart Attack and Stroke
COVID-19 has been demonstrated to be an independent risk factor for MI and ischemic stroke increasing by eightfold and sixfold in the first week following the onset of COVID-19 from exposure day (day 0). Previously it was thought to be a probable risk factor. Data from a national register for outpatients and inpatient clinics for 86,742 patients with COVID-19 between 2/1 and 9/14/ 2020 versus 348,481 matched controls were evaluated using 2 methods for risk for acute MI and stroke. This included a self-controlled case series used to compare incidence ratios for first MI and stroke prior to patients determined to have COVID-19. The other was a matched cohort study that determined the odds of acute MI or stroke in 14 days post onset of COVID-19 with a comparison to control individuals.
Some Success Reining in VITT's Deadliness Across the Pond
A high risk of mortality was seen in the UK in patients with vaccine induced immune thrombocytopenia and thrombosis (VITT) with an overall case-fatality rate of 23% observed in the first 220 cases of VITT with the Oxford- Astra Zeneca vaccine. VITT is a rare but severe thrombotic syndrome that is similar to HIT due to the production of anti-PF4 antibodies. Of those 220 patients, 17 of the most severe underwent catheter based plasma exchange to remove the PF4 antibodies resulting in a 90% survival rate. The most common therapies for VITT were anticoagulation and IV immune globulin.
Patients presented at a median of 14 days post first dose of the vaccine. The median age was 48, with 85% of people under the age of 60, with 55% women, and patients were generally healthy. Half of the patients presented with cerebral vein clots and one third had DVT and PE.
The incidence of VITT was found to be at least 1:100,000 among adults, ages 50 or older, and at least 1:50,000 for younger people. Does this mean you should not get the vaccine? The incidence of blood clots is 23% or higher in patients that get COVID, balancing the risk is very important.
Despite the Oxford-AstraZeneca vaccine not being authorized for use in the USA, it is still important to be aware of patients with low platelets, headaches, and blood clots. It is important to avoid heparin and opt for bivalirudin.
Full-Dose Heparin Benefit in Certain COVID-19 Patients Confirmed
According to the results from the REMAP-CAP, ACTIV-4a and ATTACC multiplatform trials demonstrated that a therapeutic dose of heparin was associated with an increased probability of survival for non-critically ill COVID-19 patients, but not for the most severe population. This benefit seemed to persist regardless of D-dimer level. It has been speculated that the underlying thrombotic and inflammatory damage may have been too advanced to be influenced by higher doses of heparin. The groups were also different between the three platforms, the majority of critically ill patients were from REMAP-CAP in the US, and those with moderate disease were from ATTACC and ACTIV-4 in the US and Brazil. As a result the data do not support the use of heparin to prevent thrombosis in critically ill patients, but other thrombotic or profibrinolytic therapeutics may be beneficial.
FDA Okays New PAD Indication for Rivaroxaban (Xarelto)
The FDA has expanded the indication for use of rivaroxaban to include peripheral artery disease revascularization. The approved regimen includes 2.5mg of rivaroxaban with 100mg of aspirin once daily. This utility of the dual pathway of inhibition have been demonstrated in the VOYAGER PAD and COMPASS clinical studies which targeted both platelets and thrombin. Rivaroxaban now has nine indications in the United States, the most of any direct oral anticoagulant.
Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic
Mayte Sánchez van Kammen, MD1; Mirjam R. Heldner, MD, MSc2; Justine Brodard, MSc3; et alAdrian Scutelnic, MD2; Suzanne Silvis, MD, PhD4; Verena Schroeder, PhD5; Johanna A. Kremer Hovinga, MD3; Saskia Middeldorp, MD, PhD6; Marcel Levi, MD, PhD7,8; Sini Hiltunen, MD, PhD9; Erik Lindgren, MD10,11; Maryam Mansour, MD12; Antonio Arauz, MD, PhD13; Miguel A. Barboza, MD, PhD14; Susanna M. Zuurbier, MD, PhD1; Diana Aguiar de Sousa, MD, PhD15; Jose M. Ferro, MD, PhD15; Urs Fischer, MD, MSc2; Thalia S. Field, MD, MHSc16; Katarina Jood, MD, PhD10,11; Turgut Tatlisumak, MD, PhD10,11; Jukka Putaala, MD, PhD9; Marcel Arnold, MD2; Jonathan M. Coutinho, MD, PhD1
Importance Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism.
Objective To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic.
Design, Setting, and Participants This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies.
Exposures Diagnosis of cerebral venous sinus thrombosis.
Main Outcomes and Measures Frequencies of admission thrombocytopenia (platelet count <150×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples).
Results Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149×103/µL) in 52 (6.0%), moderate (50-99×103/µL) in 17 (2.0%), and severe (<50×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies.
Conclusions and Relevance In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.
Non-adherence to Thromboprophylaxis Guidelines in Atrial Fibrillation
A Narrative Review of the Extent of and Factors in Guideline Non-adherence
Eyob Alemayehu Gebreyohannes; Sandra Salter; Leanne Chalmers; Luke Bereznicki; Kenneth Lee
Am J Cardiovasc Drugs. 2021;21(4):419-433.
Atrial fibrillation is the most common arrhythmia. It increases the risk of thromboembolism by up to fivefold. Guidelines provide evidence-based recommendations to effectively mitigate thromboembolic events using oral anticoagulants while minimizing the risk of bleeding. This review focuses on non-adherence to contemporary guidelines and the factors associated with guideline non-adherence. The extent of guideline non-adherence differs according to geographic region, healthcare setting, and risk stratification tools used. Guideline adherence has gradually improved over recent years, but a significant proportion of patients are still not receiving guideline-recommended therapy. Physician-related and patient-related factors (such as patient refusals, bleeding risk, older age, and recurrent falls) also contribute to guideline non-adherence, especially to undertreatment. Quality improvement initiatives that focus on undertreatment, especially in the primary healthcare setting, may help to improve guideline adherence.
Aspirin as Venous Thromboembolism Prophylaxis in Total Joint Arthroplasty
A Narrative Review of the Current Evidence
Dustin Rinehart, MD; Tyler Youngman, MD; Michael Huo, MD
Curr Orthop Pract. 2021;32(4):383-389.
The utilization of aspirin (acetylsalicylic acid ASA) as primary prophylaxis for venous thromboembolism (VTE) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in the United States has increased in concordance with the number of arthroplasty procedures being completed. The available literature regarding dosage, duration, efficacy, and safety varies considerably. This review assessed the recent published literature for both the efficacy and safety of aspirin as VTE prophylaxis. Overall, the rates of symptomatic VTE found in the literature ranged from 0.1% to 4.1%, of deep vein thrombosis (DVT) 0.1% to 3.0%, and of pulmonary embolism (PE) 0.1% to 1.5%. As for secondary outcome measures, the rate of major bleeding from either a gastrointestinal source or at the surgical site ranged from 0% to 3.2%, and the rate of transfusion between 7.0% to 20.0%. Among the studies that reported the infection rates, it ranged from 0.1% to 6.1%. The 90-day mortality rate was 0% to 0.23%. The available data and evidence remain inconclusive with regard to ASA dosage or the duration for patients after TKAs and THAs. However, ASA appears to be an effective option for VTE prevention when utilized as part of a multimodal approach to prophylaxis that includes early mobilization and mechanical compression devices.
"Pill-in-pocket" Anticoagulation for Atrial Fibrillation: Fiction, Fact, or Foolish?
Rod Passman, MD, MSCE, Circulation. 2021;143(23):2211-2213.
Decision-making about anticoagulation is among the most challenging aspects of atrial fibrillation (AF) management from the perspectives of both patients and physicians. On one hand, AF-related stroke, the most feared sequela of the arrhythmia, is more likely to be fatal or severely debilitating than strokes from other causes and can often be prevented with oral anticoagulants. On the other hand, anticoagulation causes major and minor bleeding, impacts quality of life, is costly to patients and the health care system, and has poor long-term compliance rates. Guidelines recommend lifelong anticoagulation on the basis of upstream risk factors irrespective of whether the AF burden is low from spontaneous termination or as the result of rhythm control strategies including antiarrhythmic drugs and ablation. This practice represents 1 example in medicine where identical treatment is administered without regard to the burden of disease or even in the face of disease diminution or resolution. Frequently cited reasons for this recommendation include the modest long-term success rates of rhythm control interventions, the high proportion of asymptomatic AF, and the uncertain role of the atrial myopathy that hypothetically may cause cardioembolic events independent of the arrhythmia. The rising prevalence of AF and the risks associated with this "1-size fits all" strategy make clear, however, that innovative approaches are needed and will have increasing importance over time.