October 2022: New In Coagulation

by Donna Castellone, MS, MT (ASCP) SH • September 28, 2022

The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica.

Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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Stronger Antiplatelet Better for VTE Prophylaxis After Joint Replacement

The CRISTAL trial revealed that enoxaparin outdid aspirin for preventing symptomatic VTE after total hip or total knee arthroplasty without initial anticoagulation. Event occurred within 90 days post surgery in 3.45% of patients on aspirin versus 1.82% on enoxaparin. Specifically, results were found in a lower rate of DVT in below the knee cases. However, there were no significant differences in above the knee DVT or PE.

No difference was found between enoxaparin versus aspirin in mortality, major bleeding, 90 day readmission or reoperation. The CRISTAL trial looked at 9711 adults who had total hip or knee arthroplasty without preop anticoagulation. They were randomized to either 100mg of aspirin or 40mg of enoxaparin given within 24 hours of surgery for 35 days post hip surgery and 14 days post knee arthroplasty. Pneumatic compression calf devices were used intraoperatively and postoperatively as well as compression stockings and moblilzation on day 0 or 1 post-operatively. The study was terminated at 62% of planned enrollment which reduced the power of the study which may have impacted the ability to detect difference in clinically important VTE including a higher rate of PE in the aspirin group.

New Biomarker Flags VTE Risk in COVID-19 Patients

New research shows that elevated levels of soluble urokinase plasminogen activator receptor (suPAR) which is produced by the immune system in response to SARS-CoV-2 infection may predict the formation of clots in hospitalized patients and even in those patients with low levels of D-dimer. In 2000 adults that were hospitalized with COVID-19 had both suPAR and D-dimer levels measured over 30 days.

It was demonstrated that in patients who had blood clots suPAR levels were nearly 50% higher than those who did not have clots. Combining D-dimer results showed that 41% of patients had a low risk for VTE. More severe disease means a higher risk of clots. SuPAR is not currently available to be measured in a clinical setting.

VTE is estimated to occur in up to 26% of patients also PE remained prevalent despite stalling the progression of respiratory illness and was the direct cause of death in up to one-third of patients despite being anticoagulated. This is attributable to immunothrombosis. This occurs when viral infections induces immune dysregulation and significant vascular inflammation. D-dimer has been the most commonly used biomarker for VTE. Combining it with markers of immune dysregulation may refine risk stratification in these patients. The uPA/uPAR system is a key regulator in cross reaction between vascular inflammation, immunity and coagulatopathy. Levels appear to be three to five times higher in these patients and may be an important biomarker in these patients.

Sex Matters in Treatment Outcomes for Pulmonary Embolism

Data suggests that women who present with a PE and undergo percutaneous pulmonary artery thrombectomy have higher rate of morbidity and in hospital mortality than men. Information from 1,128,904 PE patients using the Nationwide Inpatient database was retrospectively analyzed with a primary outcome of in hospital death.

Females when compared to males were more likely older than 65, African American or Hispanic and have lower socioeconomic status. Bleeding occurred 16.9% in women versus 11.2% in men and required more transfusions. They had more vascular complications (5% versus 1.5% in men) and only 48% were discharged to home versus 60% of men. LOS was similar and these differences in outcomes is not clear. Identifying sex differences in outcomes could aid in creating sex specific approaches and procedure related aspects. For example, women could have lower baseline hemoglobin levels which may be a threshold for blood transfusion. Higher vascular complications may be due to smaller iliofemoral vessels when compared to men. Using this information may decrease these events and optimize healthcare resource use.

Low-Dose Edoxaban Curbs Stroke Risk in Elderly With AF, Despite Frailty

A subanalysis of the ELDERCARE-AF trial showed that elderly patients who are at a high risk of bleeding may benefit from a low 15-mg dose of edoxaban. Major bleeding as well as clinically relevant nonmajor bleeding were higher in edoxaban than placebo.

Data was analyzed from 944 patients who were randomly assigned to edoxaban 15mg or a placebo for 3 years. Mean age of participants was 86.6 years and 57% were women. Evaluation of physical condition was assessed and given a frailty score. There were 6.5 % of patients were considered robust and 51% were classified as nonfrail. These groups were combined.

The placebo group rate of stroke was 7.1% per patient year for frail patients and 6.1% of those who were nonfrail. SSE occurred in the edoxaban group at an event rate of 2.5% and 1.5% of nonfrail patients. However the edoxaban group consistently had fewer SSE events regardless of frailty status but more bleeding events at 3.7% in the frail group and 2.9% in the non frail.

As observed, the lower dose of edoxaban appears to have a statistically significant reduction in the incidence of stroke in the subgroup of extremely frail elderly patients. A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value."

Novel Factor XIa Inhibitors Show Promise for Bleeding Risk

Factor XIa inhibitors have been shown to minimize bleeding when added to standard dual antiplatelet therapy, however the efficacy in preventing ischemic events are less evident. The phase II study looked at three doses of asundexian (10, 20 and 50 mg) which reduced FXIa activity in a dose dependent manner to more than 90% in patients with recent acute MI without significantly increasing bleeding. In 1600 patients who received DAPT (aspirin and P2Y12 inhibitor bleeding occurring in 7.6% of patients on asundexian at 10mg, 8.1% at 20 mg and 10.5% at 50 mg and 9% in those receiving a placebo. There were 400 patients in each arm of the asundexian and 400 in the placebo with a median age of 68 years and 23% were women. The primary efficacy outcome -- a composite of cardiovascular death, MI, stroke, or stent thrombosis -- occurred in 6.8%, 6.0%, 5.5%, and 5.5% of patients, respectively. Bleeding at all doses were not statistically different when compared to patients on DAPT plus placebo. There also was no reduction in ischemic events when asundexian was compared to a placebo.There were 362 outcomes in over 1,800 patients, 19.1% in placebo patients, 18.9% in patients who received asundexian 10 mg, 22% at 20 mg, and 20.1% in those who received 50 mg.

In the phase II AXIOMATIC randomized trial treatment with FXIa inhibitor milvexian was shown to lower the risk of ischemic stroke compared with placebo in patients with a prior ischemic stroke or high risk TIA. In 2366 patients with a median age of 71 milvexian reduced the risk of clinical ischemic stroke at doses of 25 mg once daily and 25mg, 50 mg and 100 mg twice daily. There was a 30% risk reduction with doses from 25-100mg when compared to placebo.

The incidence of major bleeding was low and the rate of major bleeding for the 25mg once daily and twice daily doses were similar to the placebo with a moderate increase seen in the 50mg twice daily and above. There was no increase in severe bleeding versus placebo and no fatal bleeding in any of the study arms.

The factor Xia inhibitors seem to allow for hemostasis but not thrombosis. These studies have shown that there doesn’t appear to be any increase in bleeding risk.

Xarelto Risky in Rheumatic Heart Disease

The INVICTUS trial results showed that rivaroxaban appeared risky for treating AF in rheumatic heart disease. It increased the composite of stroke, systemic embolism, MI or death from vascular of unknown causes by a relative 25% with a rate of 8.06% compared with 6.33% per year in the vitamin K group. Stroke being more common with rivaroxaban. A disadvantage for all cause mortality was strikingly different for rivaroxaban being 72 days over the mean of 3.1 years of follow up.

The trial included 4565 patients from Africa, Asian and Latin American who presented with AF and documented rheumatic heart disease with an elevated stroke risk. The mean age was 50.5 and 72.3% were women. Patients were randomly assigned to receive rivaroxaban or Vit K antagonist. No difference was seen in major bleeding or hospitalization for heart failure. Both valve replacement surgery and mitral valve procedures were the same in both groups. Mortality differences was due to the lower rates of sudden cardiac death and death due to mechanical or pump failure in the Vit K group. This may be attributed to the Vit K group having more physician interaction due to monitoring and those in the rivaroxaban group not being monitored.

Vit K remains the preferred treatment in AF associated rheumatic heart disease.

Edoxaban lower stroke and all cause mortality when compared with Vit K antagonists in the ENVISAGE-TAVI AF trial when compared to apixaban wasn't any better than anti-platelet therapy or warfarin. It actually increased ischemic events in the ATLANTIS trial.

P2Y12 Inhibitors May Be the Better Option for Secondary Prevention in CAD

The PANTHER meta-analysis showed cardiovascular benefits with P2Y12 inhibitor monotherapy when compared to aspirin alone. The PANTHER meta-analysis included seven trials -- ASCET, CADET, CAPRIE, DACAB, GLASSY, HOST-EXAM, and TiCAB. It included 24,325 patients (mean age 64.3 years, 21.7% women), with 12,178 assigned to P2Y12-inhibitor monotherapy (clopidogrel or ticagrelor) and 12,147 to aspirin alone. The primary outcome of risk of cardiovascular death, MI and stroke occurred in 5.5% of those on P2Y12 inhibitor versus 6.3% of patients on aspirin. Major bleeding rates were similar (1.2% vs 1.4%). When these findings were combined there was a lower risk of net adverse clinical events in the P2Y12 group (6.4% vs 7.2%).

Previous studies have shown mixed results when using monotherapy including clopidogrel or ticagrelor. This seven-study patient level meta-analysis support a shift towards a single P2Y12 inhibitor. Generic P2Y12 inhibitors are now available making the cost roughly the same as aspirin. These results should apply to people who have experienced a cardiac event. In particular since the updated guidance regarding aspirin use being appropriate in high risk adults ages 40-59 but not in those 60 or older.

Full-Dose Anticoagulation Cuts VTE in Severe COVID-19

The COVID-PACT trial was a randomized control that looked at the benefit of full dose heparin compared to standard prophylactic anticoagulation in critically ill COVID patients. Included were 390 patients who required ICU level care for COVID. Of those 99% required advanced respiratory therapy. There were 15% who required mechanical ventilation which increased to 40% during hospital stay. Full dose heparin showed a 95% great likelihood of benefit when looking at both fatal and nonfatal thrombotic endpoints. This included venous or arterial thrombosis death, PE, DVT, MI, ischemic stroke, systemic embolic events and acute limb ischemia. Stronger anticoagulation didn't improve mortality but it did increase bleeding. No benefit was also seen in patients randomized to clopidogrel or no antiplatelet agent. The trial was terminated early at about 50% of planned enrollment. Limitations also include exclusion of patients with a high bleeding risk.

The ACT trial was a randomized study that looked at microvascular risk which used a combination of colchicine as an anti-inflammatory together with aspirin and low dose rivaroxaban. The ACT Inpatient trial included 2,500 adults with symptomatic, laboratory-confirmed COVID-19 enrolled within 72 hours of admission or clinical worsening. It was conducted on both inpatients and outpatients. They were randomized to colchicine plus rivaroxaban and aspirin, colchicine and control, the antithrombotics plus control, or neither active medication for 28 days. On the inpatient portion of the trial colchicine had no impact on need for high flow oxygen or mechanical ventilation or death. Additionally, the antithrombotic comparison proved no better than control for the primary endpoint of major thrombosis in the analysis. There was more bleeding with the antiplatelet/anticoagulant combination. While mortality and any thrombosis were similar between groups for both treatments and patient types.

In the outpatient portion of the ACT trial included 3500 high risk adult greater than 30 with symptomatic, laboratory confirmed COVID-19. They were randomized to colchicine or no colchicine with factorial randomization to aspirin or no aspirin. Colchicine had no impact on hospitalization or death. The randomization to aspirin also did not impact the primary endpoint. Upon subgroup analysis there was no population which benefit was greater for either treatment. Limitations of the ACT trial include the use of a control group without placebo and lower-than-anticipated event rates.

Currently, there are several guidelines that discuss anticoagulation in COVID-19 with conflicting recommendations which have been guided by endpoints focused on COVID survival and disease progression. The ISTH recommends no direct OAC use or antiplatelet agents for prophylaxis with prophylactic dose in the ICU and therapeutic dose in general wards. Confusion arises when patients are on full dose heparin in the hospital and then what happens when they move to the ICU?

The results of the study should raise confidence that full dose anticoagulation in a critically ill population is very effective for reducing thrombotic complications. But again it is important to know which group of patients to use this on, you don't want to increase the risk of bleeding. It is important to balance the risk of thrombosis versus bleeding.

Blood Type Tied to Early-Onset Stroke Risk

A meta-analysis of genome-wide association studies (GWAS) demonstrated that two variants in ABO, a known stroke locus were linked with early onset ischemic stroke risk. It included 48 GWAS of 16,730 stroke cases and 599,237 healthy non-stroke controls. Up to a third of the samples were people of non-European ancestry increasing the racial diversity to reflect disparities in Black and Hispanic populations. There were 5825 stroke cases that were early onset (18-59) and 9269 occurred at 60 or older.

They were subgroups O1 and A1 and effect sizes were significantly larger in early onset than late onset, over the age of 60, stroke. Results showed the odd for O1 at 0.88 for early and 0.96 for late stroke while A1 was 1.16 for early versus 1.05 for late onset stroke. Results point to prothrombotic mechanisms in younger stroke patients.

Non-O blood types have been linked to an early risk of stroke, but the link is more strongly associated with early stroke and mostly in blood type A. The people with these gene variants are more likely to develop blood clots which can lead to stroke.

VTE Risk Not Elevated in AD Patients on JAK Inhibitors: Study

A systemic review and meta-analysis has shown that in patients with atopic dermatitis (AD) being treated with Janus kinase (JAK) inhibitors do not appear to be at an increased risk of VTE. Previously the results of the ORAL Surveillance study in patients with rheumatoid arthritis (RA) treated with JAK inhibitors were required by the FDA to add a boxed warning which included an increased risk of serious heart-related events including heart attack, stroke, cancer, blood clots and death. However, despite these findings, some dermatologists are still urging caution. JAK inhibitor trials are short term and there still needs to be an awareness of risk associated with these medications.

The meta-analysis looked at the risk of VTE in untreated patients with AD compared with non AD patients as well as the risk of VTE in AD patients with JAK inhibitors compared to those on placebo or dupilumab. The JAK inhibitors included were abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

In reviewing two studies of 458,206 participants it was found that the overall incidence rate of VTE in patients with AD was 0.23 events per 100 patient years, which did not differ from non-AD patients. Upon review of another 15 studies and 8787 participants with AD no difference in the rate of VTE were found in patients on JAK inhibitors versus those on placebo or dupilumab.

More long term data is needed, however these finding should help to provide reassurance that based on this information there is no increased VTE risk in patients treated.

Flu Shots Tied to Lower Stroke Risk

A study out of Spain showed that older adults who received an influenza vaccine were 12% less likely to have an ischemic stroke when compared to those who were not vaccinated. The risk reduction occurred within 15-30 days.

This observation study shows those who get a flu shot have a lower stroke risk, however it needs to be determined if it is due to the protective effect of the vaccine or to other factors. It has been thought that acute systemic inflammation may drive this relationship, possibly through endothelial dysfunction, atherosclerotic plaque instability, and a pro-coagulant state.

This study compared 14,322 people who had a first stroke and no cancer history from January 2002 through December 2015 with 71,610 age and sex matched controls. There were 9542 non-cardioembolic stroked and 4780 were cardioembolic. Patients were classified as vaccinated in they had a flu shot 14 days prior to their index stroke. There were 41.4% of stroke patients and 40.5% of controls were vaccinated. Vaccinated people had a higher prevalence of vascular risks, diseases and co-medication than non-vaccinated people. Reduced risks were seen for both types of strokes in vaccinated people. This points to evidence that older individuals with medical comorbidities may have a moderately reduced risk of ischemic stroke after a flu shot.


Innovative Treatment Utilizing an Autologous Blood Clot for Diabetic Foot Ulcers

Marie Williams, DPM; David Davidson, DPM; Naz Wahab, MD; Jessie Hawkins, PhD; Chinenye D. Wachuku, DPM; Robert Snyder, DPM

Wounds. 2022;34(7):195-200.


Introduction: Diabetic foot ulcer is a complex wound that requires considerable effort to restart a stalled healing process. In this study, a TABCT product was used in a point-of-care setting to treat DFUs by reconstructing the ECM and adjusting intricate phenotypes and mechanisms of mediators to progress towards complete healing. The mechanism of action consists of reconstruction of the ECM, which protects the wound area from further destruction while it incorporates into the ulcer to promote granulation over exposed vital structures (ie, tendons, bone, and neurovascular structures).

Objective: The authors evaluated the efficacy of the TABCT product in the management of DFUs.

Materials and Methods: Study participants were wound care patients in hospitals and clinics across the United States and Israel as part of a registry study (ClinicalTrials.gov: NCT04699305). Twenty-nine patients age 18 years or older with chronic DFUs were included. A blood clot was created using the patient's own peripheral blood in a point-of-care setting. An 18-mL blood sample was drawn from the patient and incorporated with calcium gluconate and kaolin to form a clot. Efficacy and superiority levels in PAR at week 4 and week 12 over the SOC treatment were established using the Agresti-Coull confidence interval.

Results: Treatment of DFUs using the TABCT product resulted in 22 patients (75.86%) achieving 50% PAR at week 4 and showed superiority when compared with SOC data in previously published studies. Complete closure was achieved in 28 wounds (95%) at week 12.

Conclusion: In the current study, TABCT exhibited superiority over SOC treatment and provided granulation over vital structures with a reduction in overall wound size in a timely manner via incorporation and stimulation of the body's own healing capabilities

The Need to Standardize Our Language Around Dual Antiplatelet Therapy—A Call to Action

Enrico G. Ferro, MD1,2; Davide Capodanno, MD3; Robert W. Yeh, MD1,2

JAMA Cardiol. Published online August 24, 2022. doi:10.1001/jamacardio.2022.2711

"Everything should be made as simple as possible, but not simpler." The words of Albert Einstein as paraphrased by Roger Sessions capture the problem clinicians currently face when describing dual antiplatelet therapy (DAPT) for patients with coronary artery disease. At first, this acronym carried an intuitive meaning that simplified communication with colleagues and patients. Over the last 2 decades, however, the science of DAPT has become more nuanced, while our terminology has lagged behind. Whether in catheterization reports or clinic notes, clinical trials or meta-analyses, our community commonly focuses its attention on DAPT duration, but often neglects to answer other key questions, such as what combination of antiplatelet agents should we use during DAPT treatment? How and when should we switch to a new regimen? When DAPT is completed, what is the single antiplatelet therapy (SAPT) of choice for patients? DAPT has become an ambiguous acronym that oversimplifies a rapidly evolving science. We believe that a more granular terminology is needed to avoid dangerous assumptions in patient care or clinical research, together with a multidisciplinary effort to standardize this terminology in our scientific community.

Worldwide Trends in Antithrombotic Therapy Prescribing for Atrial Fibrillation

Leona A. Ritchie; Deirdre A. Lane; Gregory Y.H. Lip

Europace. 2022;24(6):871-873.

The landscape of atrial fibrillation (AF) management has changed substantially over the last decade. Key milestones for stroke prevention have included the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs), replacement of the CHADS2 stroke risk assessment with CHA2DS2-VASc, guideline updates to offer oral anticoagulants (OAC) to prevent AF-related stroke instead of antiplatelet therapy, and a preference to prescribe NOAC instead of VKA. These changes have increased the proportion of OAC eligible AF patients and have been the catalyst for the 'transition era', where we have moved away from a period dominated by VKA use for stroke prevention, to a new era of NOACs. In addition, adherence to more holistic approach to AF management, based on the Atrial fibrillation Better Care (ABC) pathway is associated with improved outcomes, including a reduction in stroke.

Timeline of key milestones including oral anticoagulant approvals and updates to European, Asian, and American guidelines on atrial fibrillation. ACC/AHA/HRS, American College of Cardiology/American Heart Association/Heart Rhythm Society; APHRS, Asia Pacific Heart Rhythm Society; CHADS2, stroke risk assessment scoring 1 point each for history of heart failure, hypertension, diabetes, age ≥75 years, and 2 points for history of stroke/transient ischaemic attack; CHA2DS2-VASc, stroke risk assessment scoring 1 point each for female gender, age 65–74 years, history of heart failure, diabetes, hypertension, vascular disease, and 2 points each for history of stroke/transient ischaemic attack/venous thromboembolism and age ≥75 years; EMA, European Medicines Agency; ESC, European Society of Cardiology; FDA, Food and Drug Administration; NMPA, National Medical Products Administration (formerly the China Food and Drug Administration); NOAC, non-vitamin K antagonist oral anticoagulant; PMDA, Pharmaceuticals and Medical Devices Agency; VKA, vitamin K antagonist.

In the latest guidelines, NOACs are recommended as the default stroke prevention strategy for all eligible AF patients, except those at low risk of thrombo-embolic events (defined as a CHA2DS2-VASc of 0 in males or 1 in females). Non-vitamin K antagonists continue to be the only treatment option in people with antiphospholipid syndrome, advanced chronic kidney disease (creatinine clearance <15 mL/min), rheumatic mitral valve disease, or mechanical heart valves.

In the current issue of Europace, Grymonprez et al. performed a systematic review and meta-analysis of worldwide antithrombotic (VKA, NOAC, antiplatelet) prescribing patterns for AF between 2010 and 2018. The review included 21 observational cohort studies set in Europe (n = 11), North America (n = 3), Asia (n = 4), Oceania (n = 1), or South America (n = 1), and one worldwide study. The annual prevalence and incidence of OAC use were reported for 9 758 637 and 197 483 non-selected AF patients eligible for OAC, respectively.The authors use the term 'non-selected AF patients' to describe the exclusion of studies that reported on selected AF subgroups, including people with chronic kidney disease, dementia, a history of stroke/bleeding, older people, or those receiving interventions such as ablation or percutaneous coronary intervention.

Comparison of Patient Outcomes Before and After Switching From Warfarin to a Direct Oral Anticoagulant Based on Time in Therapeutic Range Guideline Recommendations

Brian Haymart, MS, RN,1 Geoffrey D. Barnes, MD, MSc,1 Xiaowen Kong, MS,1 Mona Ali, PharmD,2 Eva Kline-Rogers, MS, NP,1 Deborah DeCamillo, RN, BSN,1 and Scott Kaatz, DO, MSc3

JAMA Netw Open. 2022 Jul; 5(7): e2222089.

This cohort study evaluates stroke and major bleeding rates before and after switching from warfarin to a direct oral anticoagulant (DOAC) in patients grouped by pre-switch time-in-therapeutic range guideline thresholds.


Direct oral anticoagulants (DOACs), including apixaban, dabigatran, edoxaban, and rivaroxaban, are recommended instead of warfarin in patients newly diagnosed with nonvalvular atrial fibrillation (NVAF).1,2 However, it is less clear which established patients taking warfarin should switch to a DOAC. Medical societies have provided some guidance when considering switching to a DOAC based on time in therapeutic range (TTR): the European Society of Cardiology (TTR<70%), the American College of Chest Physicians (TTR<65%), and the American College of Cardiology (TTR<58%).1,2,3 Our objective was to use the Michigan Anticoagulation Quality Improvement Initiative clinical registry to evaluate stroke and major bleeding rates before and after switching from warfarin to a DOAC in patients grouped by pre-switch TTR guideline thresholds.


The registry is part of a Blue Cross Blue Shield of Michigan–sponsored quality improvement collaborative.4 Funded abstractors at 6 participating anticoagulation clinics with institutional review board approval enter patient data into the registry. Our study cohort included patients initiated on warfarin for NVAF who were later switched to a DOAC between 2010 and 2021. Patients were excluded if NVAF was not the only indication for anticoagulation or if they did not have at least 6 months of follow-up after switching to a DOAC. The outcomes assessed were ischemic stroke and major bleeding based on International Society of Thrombosis and Hemostasis criteria.5 This report follows the STROBE reporting guideline. This study received a waiver of participant consent from the institutional review board because of minimal risk to participants.

TTR was calculated using the Rosendaal method,6 and patients were grouped based on guideline TTR thresholds. Each group’s outcome rates (number per 100 patient-years) while taking warfarin were compared with rates after switching to a DOAC. Rates of major bleeding were adjusted by a modified HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) score (as continuous variable-removing the labile INR) while rates of ischemic stroke were adjusted by CHA2DS2-VASc score (as continuous variable) and compared using a mixed model with patients as random effect.5

Categorical variables were assessed using χ2 test or Fisher exact test. Two-sided P<.05 was considered significant for all comparisons. All statistical analyses were performed using SAS version 9.4 (SAS Institute) and R version 3.6.3 (R Project for Statistical Computing).


Of 6628 patients with NVAF taking warfarin, 524 (7.9%) meeting inclusion criteria switched to a DOAC. At the time of switch, the mean (SD) age was 73.3 (10.7) years, 231 (44.1%) were female, and 168 (35.2%) had at least moderate chronic kidney disease (creatinine clearance<60 mL/min [to convert to mL/s/m2, multiply by 0.0167]) (Table 1). Apixaban was the predominant DOAC that patients switched to (277 patients [52.9%]), followed by rivaroxaban (146 patients [27.9%]).

In all but the group with TTR less than 65%, the rate of major bleeding was significantly higher after switching (Table 2). The groups with TTR less than 70%, TTR less than 65%, and TTR less than 58% had major bleeding rates of 3.8, 4.9, and 5.8 per 100 patient-years while taking warfarin compared with 5.8, 6.3, and 7.5 per 100 patient-years after switching to a DOAC, respectively. Gastrointestinal hemorrhage accounted for 58.3% of bleeding before and 59.7% after switching, whereas 11.1% of bleeding before and 13.9% after switching were intracranial. In all TTR groups, there was no significant difference in ischemic stroke before and after switching. The group with TTR less than 70% had an ischemic stroke rate of 1.5 per 100 patient-years while taking warfarin and 2.0 per 100 patient-years after switching; for TTR less than 65%, the rates were 1.9 (before) and 1.6 (after); and for TTR less than 58%, they were 2.1 and 1.6.

Anticoagulation management of post-cardiac surgery new-onset atrial fibrillation

Ghaith Alhatemi1, Mohamed Zghouzi2, Yasar Sattar3, Bachar Ahmad2, Waqas Ullah4, M Chadi Alraies5

Cleve Clin J Med. 2022 Jun 1;89(6):329-335. doi: 10.3949/ccjm.89a.21003.


New-onset post-cardiac surgery atrial fibrillation (PCSAF) is a frequent complication with estimated incidence of 17% to 64%, depending on type of surgery. It is associated with higher mortality, morbidity, and predisposition to stroke and systemic embolism postoperatively. Standard care involves rate or rhythm control, in addition to antithrombotic therapy in those with history of stroke, transient ischemic attack, or high risk of systemic thromboembolism. However, risk of bleeding is not negligible, and treating physicians should weigh the risks and benefits before committing to postoperative anticoagulation therapy. More investigations are warranted to explore antithrombotic therapy benefit, particularly postoperative anticoagulation, considering the potentially self-limited nature of the arrhythmia and high risk of postoperative bleeding.