November 2022: New In Coagulation

by Donna Castellone, MS, MT (ASCP) SH • November 15, 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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Golden State Medical Supply, Inc. Issues a Voluntary Nationwide Recall of Atenolol 25 mg Tablets and Clopidogrel 75 mg Tablets Due to a Label Mix-up

A voluntary recall of the following products have been initiated for Clopidogrel lot number GS046745 which was mislabeled as Atenolol 25mg tablets.

Atenolol is used for hypertension versus clopidogrel being used to lowere the risk of stroke, blood clot or serious heart problem. Patients who stop taking atenolol are at an increased risk for ischemic, hypertensive and arrhythmic adverse events. Additionally, these patients may already be on an anticoagulant and at a increase risk for bleeding.

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax. Complete and submit the report Online:

Making Low-Dose tPA Work for Japanese DOAC Users With Ischemic Stroke

An observational study from Japan demonstrated that IV thrombolysis could be given to patients with an ischemic stroke even within one day of direct oral anticoagulant therapy. The registry looked at consecutive patients from 2011-2021 who presented at a stroke center and were admitted 7 days from symptom onset. There were 793 patients who received IV thrombolysis and of those 753 had not taken any DOACs within 24 hours of stroke. DOAC users had a mean age of 80 versus 76, more frequently had AF as well as both congestive heart failure and prior strokes when compared to those who did not use DOACs. There were no more major hemorrhagic events (2.5% vs 1.1%) or mortality at 3 months (5.0% vs. 5.7%) between groups.

The comparison of ICH were comparable at 2.5% and 2.4% after alteplase administration. Japan, however, does use a lower does of alteplase (0.6 mg/kg) while also allowing IV thrombolysis at least 4 hours after a DOAC dose in select patients. This may not make the results transferrable to other countries using the 0.9 mg/kg dose. Results need to be confirmed in larger, multi-center prospective studies.

Risk of blood clots remains for almost a year after COVID-19 infection, study suggests

Research from the Universities of Bristol, Cambridge and Edinburgh concluded that COVID-19 increased the risk of blood clots for at least 49 weeks. It also suggests that the pandemic may have led to an additional 10500 cases of heart attacks, stroke as well as DVT and other blood clot complications. These findings were based on the health records of 48 million unvaccinated adults during the first wave of the pandemic. The data was prior to the Delta and Omicron variants.

It was seen that after the first week of a COVID-19 diagnosis, people were 21 times more likely to have a heart attack or stroke. This dropped to 3-9 times more likely after 4 weeks. The risk of DVT and PE was found to be 33 times greater in the first week and dropped to 8 after four weeks. The higher risk of blood clots after COVID-19 remained for the study duration, although by 26 to 49 weeks it had dropped to 1.3 times more likely for clots in the arteries and 1.8 times more likely for clots in the veins. Previous research looked at only hospitalized COVID-19 patients. New studies show that there was also an effect on people whose COVID did not lead to hospitalization however it was not as great as for those who had severe disease.

Brief Anticoagulation Preserves Radial Artery After Catheter Access

The RIVARAD trial from Tunisia looked at 538 patients getting a tranradial coronary angiography or percutaneous coronary intervention. The participants had a mean age of 60, 32% were female which is a known predictor of radial artery occlusion. More than 50% had longer than 6 hours to hemostasis and a quarter had a prior transradial procedure, half were smokers and half had diabetes. Patients were randomized to 10 mg of rivaroxaban for 7 days post-procedure or standard of care without anticoagulant.

Results showed that a short course of rivaroxaban post transradial coronary procedure prevented radial artery occlusion complications. It reduced 30 day radial artery occlusion by half (6.9% vs 13%). However, hemorrhagic complications were more common (2.7% versus 1.9%) but it was not considered significant since most were minor and no bleeding events occurred in patients who just received rivaroxaban without an antiplatelet agent.

The trial excluded patients at a high bleeding-risk. More information will be available in the CAPITAL-RAPTOR trial which will randomize 1800 patients to 15 mg rivaroxaban or standard care without anticoagulation post transradial procedures.

Stopping aspirin when on a blood thinner lowers risk of bleeding, study finds

Researchers in Michigan have analyzed over 6700 patients treated with anticoagulant for VTE. Patients were treated with warfarin but also took aspirin. During the study aspirin consumption decreased by 46.6%. As a result the risk of bleeding dropped by 32.3% or one major bleeding event prevented per every 1000 patients who stop taking aspirin. Several other studies have also found by eliminating aspirin bleeding risk decreases.

One study showed that in patients taking both aspirin and warfarin for AF and VTE had more bleeding events and ER visits for bleeding than those taking warfarin alone. The same was seen in patients taking aspirin and DOACs. They were more likely to have a bleeding event but not less likely to have a blood clot.

Clot Grabber Safe, Promising in Intermediate-Risk PE

The FLASH registry showed that clot retrieval for intermediate to high risk PE patients who don't fill conventional criteria for intervention was safe and associated with immediate hemodynamic and symptom benefits. There were no device related deaths in 800 patients (mean age 61, 54% male) having mechanical thrombectomy using the FlowTreiver system. There were major AE in 1.8% of patients. The mortality rate was 0.3% at 48 hours, and four other deaths at the 30-day follow-up, however none were related to the device. The 30-day all cause readmission rate was 6.2% with 1.4% related to PE treatment.

Current PE guidelines have supported thrombectomy only for patients who decompensate or have contraindications to thrombolytics. Clinical outcomes need to be evaluated in randomized clinical trials and not just for the device used in the study. Comparison of the procedure to the standard of care of treatment, thrombolytics or heparin are needed looking at the endpoints of mortality and ICU stay. The PEERLESS trial should help to provide this evidence.

Heparin Pretreatment May Safely Open Arteries Prior to STEMI Cath

An analysis of 40,000 Swedish patients with STEMI was conducted. The 38% of patients who were given heparin before arrival in the cath-lab were 11% less likely to show IRA occlusion at angiography prior to PCI. Additionally, there was a 13% lower 30 day mortality rate than patients started on heparin in the cath lab, while their risk of bleeding did not increase.

The open infarct related artery (IRA) on cath-lab arrival allows STEMI an opportunity for earlier reperfusion and a chance for smaller infarcts and possible improved clinical outcomes. The pre-treatment group did not have more major bleeds, the risk increased significantly in patients older than 75 or who weighed less than 132 pounds, or if catheterization was performed via another access route other than the radial artery. In this patient population, extra caution should be used if they have received heparin prior to arrival in the cath-lab.

Results point to the pretreatment with heparin might be a good option to improve patency of infarct related arteries in STEMI. Randomized controlled clinical trial would provide a definitive answer. This was an observational study.

Antithrombotics Tied to Post-Colonoscopy Clotting

Patients who are currently on antithrombtic agents which are temporarily stopped presented with a higher risk of thromboembolic events post 30 days colonoscopy. Results were collected retrospectively from 6000 patients. Median age was 64, and 52% were men. Common comorbidities included hypertension (25%), ischemic heart disease (10%), and atrial fibrillation (6%). Of these patients, 28.2% received antithrombotic therapy; 7.8% were taking anticoagulants, 19.6% were taking antiplatelets, and 0.76% received various combinations of antiplatelets and anticoagulants. It was especially high in those who presented with an underlying high risk of thromboembolic events. The highest events occurred in patients taking dual antiplatelet therapy (4.65%), and clopidogrel monotherapy (2.78%) versus those not on an antithrombotic (0.11%). The overall event rate was 0.85% on any anti-thrombotic. There were 0.4% of patients developed post colonoscopy bleeding with the highest risk on those on aspirin or DOACs.

Current guidelines from the American College of Gastroenterology recommend in these patients undergoing elective endoscopy to continuing warfarin but temporarily stopping DOACs.

Will Factor XI Be the Goldilocks Anticoagulant Target?

Factor XI may be an ideal anticoagulant. Factor XI is part of the contact pathway and it doesn't have much to do with controlling bleeding but is critically important for thrombus formation. The hypothesis is that targeting FXI may allow the prevention of a pathologic clot from forming but still allow normal clot formation. This will need to be demonstrated in a randomized trial.

How can something stop clot formation or block thrombin formation- which occurs during amplification, but not impact bleeding? An example is during a crush injury to tissue a massive amount of thrombin is generated via tissue factor pathway. But, in an acute coronary event due to plaque embedded in the wall of a vessel, there is a small amount of thrombin generated which is insufficient alone to cause an occlusive thrombus. The thrombin needs to be amplified to generate sufficient thrombin to cause a thrombus which requires FXI.

A FXI deficiency is known as Hemophilia C. These patients seldomly bleed even at levels of 1-2%, but there are some exceptions. This prompted the idea to selectively lower FXI to very low levels. This can be done three different ways, the first is with an antibody that binds to FXI to get rid of FXI resulting in lower levels. The second method is an antisense oligonucleotide which stops the cell from producing FXI. Both methods are given by injection. The final method is an oral medication that targets FXIa using small molecules. Currently they are in phase 2 trials demonstrating low rates of bleeding. Studies however are not powered for clinical events.

The biggest question is will this class of drugs be effective to warrant them replacing the current DOACs? The biggest clinical advantage is if the FXI methodology would produce less bleeding. Some patients are not treated for AF due to bleeding concerns. Phase 3 trials should help to demonstrate this.

PROACT Xa Trial of Apixaban With On-X Heart Valve Stopped

The PROACT Xa clinical trial has been stopped based on the recommendation of independent data and safety monitoring board. The trial looked at whether patients with an ON-X mechanical aortic valve could be managed on apixaban versus warfarin. Warfarin is the only approved anticoagulant with mechanical valves. This was due to a lack of evidence supporting noninferiority of apixaban over warfarin for valve thrombosis and thromboembolism.

In the trial patients were randomly assigned to either warfarin or apixaban. Results showed that blood clots resulting in stroke occurred more frequently in patients receiving apixaban and that the study was unlikely to achieve its primary endpoint without exposing people to risk.

NHSBT researchers discover new blood group system

The NHSBT and the University of Briston have discovered a new rare blood group system called Er that have been linked to tow 30 year old cases of hemolytic disease of the fetus and newborn. Individuals with alloantibodies against several antigens- Era, Erb and Er3 were first observed 30 years ago using a technique that allowed for simultaneous analysis of gene coding DNA sequences which identified specific changes in the gene coding for the PIEXO1 protein. This resulting in the production of an alter protein on their cell surface.

Researchers in Bristol used gene editing in an immortalized cell-line. They then removed and reintroduced the PIEZO1 protein to prove that alloantibodies to Er antigens (including two novel high-incidence antigens: Er4 and Er5) bind to PIEZO1. They also confirmed that PIEZO1 is required for Er antigen expression. These variants are extremely rare.

3-Year Results Support Dropping Aspirin After PCI

The SMART-CHOICE trial compared two antiplatelet strategies. It looked at 3 months of DAPT followed by long term P2Y12 inhibitor monotherapy or prolonged DAPT for 12 months or longer. The trial was conducted in 2993 patients who underwent PCI with a drug eluting stent. Dual therapy with aspirin and P2Y12 inhibitor post PCI with a drug eluting stent is crucial to reducing the risk of ischemic events but there is a concern about bleeding.

Analysis of the data at 12 months showed similar rates of ischemia with both strategies but a lower rate of bleeding in patients with shorted DAPT. The report of the 3 year results show similar outcomes. At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction (MI), or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group. Bleeding was reduced in the shortened DAPT group at 3.2% versus 8.2% in the prolonged DAPT group. This is the first trial to report on the long term safety and efficacy of P2Y12 monotherapy.

These results support evidence of dropping aspirin with indefinite use of P2Y12 inhibitor in this PCI patient cohort. This has also been demonstrate in the HOST-EXAM and GLOBAL LEADERS trials. As a result of these findings the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as class IIa indication.

Unexplained Bleeding Linked to Rat Poison in Synthetic Cannabinoids

A total of 52 cases were reported due to unexplained bleeding in dozens of patients with a history of synthetic cannabinoid (SCB) use. This was linked to poisoning with brodifacoum which is an anticoagulant often used in rat poison. These cases were reported in Florida. The mean age was 36 and 76.9% were men.

Patients were interviewed and medical records were reviewed to collect information on signs and symptoms, marijuana or other drug use, product purchase locations, and potential exposure to prescription vitamin K oxidoreductase antagonists. Of those patients 83% were confirmed and included four patients who died. Symptoms included hematuria, abdominal pain and hematemesis including elevated INRs.

There were 47 patients who reported using SCBs that were purchased at similar locations prior to onset. There were five patients who provided the SCB products they had smoked four of which were positive for brodifacoum. Patients were treated with vitamin K1 administered orally and IV to treat the coagulopathy.

Testing for brodifacoum poisoning is difficult and expensive at around $750/test with a long turn around time and offered by a single laboratory.

Stroke, clot risk halved in patients with heart disease and arrhythmia who took blood thinners apixaban versus rivaroxaban

A study has determined that apixaban has demonstrated superiority to rivaroxaban in patients presenting with stroke or systemic embolism in patients with AF and valvular heart disease. This was visible after the first year that patients were on apixaban. Data analysis looked at patients with AF and associated valvular heart disease taking these anticoagulants. The study revealed that those who took apixaban had their clot risk decreased by almost half when compared with those on rivaroxaban.

This was a study that looked at 10,000 patients on apixaban compared with 10000 patients taking rivaroxaban. This was not a randomized trial but were age and characteristic matched in each group. Medical records were reviewed.from 2013-2020. Results showed in the apixaban group there was a 43% decreased risk of clotting and a 49% lower risk of GI or ICH bleeding. Evidence was shown in as early as six month follow up with an increase in events in the rivaroxaban group. The rate of stroke or systemic embolism per year of follow up was 0.91% in the rivaroxaban group versus 0.52% in the apixaban users.


High Incidence and Unique Features of Cerebral Venous Sinus Thrombosis in Hospitalized Patients With COVID-19 Infection

Margy E. McCullough-Hicks, MD; Daniel J. Halterman, MS; David Anderson, BSAE; Kenneth Cohen, MD; Kamakshi Lakshminarayan, MBBS, PhD

Stroke. 2022;53(9):e407-e410.


Background: Cerebral venous sinus thrombosis (CVST) secondary to vaccine-induced thrombotic thrombocytopenia is an extremely rare side effect of adenovirus-based COVID-19 vaccines. CVST incidence associated with COVID-19 itself has not been widely reported. We report the incidence of CVST in patients hospitalized with COVID-19 during the first year of the pandemic.

Methods: We analyzed de-identified electronic medical records of a retrospective cohort of patients admitted with COVID-19 to >200 hospitals between March 2020 and March 2021. We used International Classification of Diseases, Tenth Revision codes and natural language processing extracts to identify patients with a new CVST diagnosis during COVID-19 hospitalization. The primary outcome was CVST incidence in hospitalized, COVID-19-positive patients. Secondary outcomes included CVST incidence and mortality. Incidence rates were calculated using the DerSimonian-Laird estimator method.

Results: Ninety-one thousand seven hundred twenty-seven patients were evaluated; 22 had new CVST diagnoses by electronic medical record review. CVST incidence in the hospitalized COVID-19 cohort was 231 per 1 000 000 person-years (95% CI, 152.1–350.8). Females<50 had the highest incidence overall (males <50: 378.4 [142–1008.2]; females<50: 796.5 [428.6–1480.4]). In patients ≥50 years old, males had a higher estimated CVST incidence (males≥50: 130.5 [54.3–313.6]; females≥50: 88.8 [28.6–275.2]). Older patients (45.5% of patients ≥50 versus 0% of <50 years of age, P=0.012) and males (44.4% of males versus 7.7% of females, P=0.023) were more likely to die in hospital.

Conclusions: CVST incidence in COVID-19–positive hospitalized patients is high. Advanced age and male gender were associated with likelihood of death in hospital; further studies are required to confirm these findings.

Long-term Effects of P2Y12 Inhibitor Monotherapy After Percutaneous Coronary Intervention - 3-Year Follow-up of the SMART-CHOICE Randomized Clinical Trial

Ki Hong Choi, MD1; Yong Hwan Park, MD2; Young Bin Song, MD, PhD1; et alTaek Kyu Park, MD1; Joo Myung Lee, MD1; Jeong Hoon Yang, MD1; Jin-Ho Choi, MD1; Seung-Hyuk Choi, MD1; Ju-Hyeon Oh, MD2; Woo Jung Chun, MD2; Woo Jin Jang, MD3; Eul-Soon Im, MD4; Jin-Ok Jeong, MD5; Byung Ryul Cho, MD6; Seok Kyu Oh, MD7; Kyeong Ho Yun, MD7; Deok-Kyu Cho, MD8; Jong-Young Lee, MD9; Young-Youp Koh, MD10; Jang-Whan Bae, MD11; Jae Woong Choi, MD12; Wang Soo Lee, MD13; Hyuck Jun Yoon, MD14; Seung Uk Lee, MD15; Jang Hyun Cho, MD16; Woong Gil Choi, MD17; Seung-Woon Rha, MD18; Hyeon-Cheol Gwon, MD1; Joo-Yong Hahn, MD, PhD1; for the SMART-CHOICE Investigators

JAMA Cardiol. Published online September 28, 2022. doi:10.1001/jamacardio.2022.3203


Importance Although P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable.

Objective To identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI.

Design, Setting, and Participants The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020.

Interventions Patients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer.

Main Outcomes and Measures The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5).

Results In total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P=.69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P<.001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P=.048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

Conclusions and Relevance Among patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size.

Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism - The CANARY Randomized Clinical Trial

Parham Sadeghipour, MD1,2; Yaser Jenab, MD3; Jamal Moosavi, MD1; et alKaveh Hosseini, MD3; Bahram Mohebbi, MD1,4; Ali Hosseinsabet, MD3; Saurav Chatterjee, MD5,6; Hamidreza Pouraliakbar, MD7; Shapour Shirani, MD3; Mehdi H. Shishehbor, DO, MPH, PhD8; Azin Alizadehasl, MD4; Melody Farrashi, MD9; Mohammad Ali Rezvani, MD7; Farnaz Rafiee, MD7; Arash Jalali, PhD3; Sina Rashedi, MD, MPH1,3; Omid Shafe, MD1; Jay Giri, MD, MPH10; Manuel Monreal, MD, PhD11; David Jimenez, MD, PhD12,13,14; Irene Lang, MD15; Majid Maleki, MD1; Samuel Z. Goldhaber, MD16,17; Harlan M. Krumholz, MD, SM18,19,20; Gregory Piazza, MD, MS16,17; Behnood Bikdeli, MD, MS16,17,20,21

JAMA Cardiol. Published online October 19, 2022.

Importance The optimal treatment of intermediate-high–risk pulmonary embolism (PE) remains unknown.

Objective To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high–risk PE.

Design, Setting, and Participants The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High–Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high–risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020.

Interventions Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy.

Main Outcomes and Measures The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes.

Results The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P=.24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P=.01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P=.01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P=.048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group.

Conclusions and Relevance This prematurely terminated randomized clinical trial of patients with intermediate-high–risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial.

Association of Race and Ethnicity With Oral Anticoagulation and Associated Outcomes in Patients With Atrial Fibrillation - Findings From the Get With The Guidelines–Atrial Fibrillation Registry

Utibe R. Essien, MD, MPH1,2; Karen Chiswell, PhD3; Lisa A. Kaltenbach, MS3; et alTracy Y. Wang, MD, MHS, MSc3; Gregg C. Fonarow, MD, MSc4,5; Kevin L. Thomas, MD3; Mintu P. Turakhia, MD, MAS6,7; Emelia J. Benjamin, MD, ScM8,9; Fatima Rodriguez, MD, MPH10; Margaret C. Fang, MD, MPH11; Jared W. Magnani, MD, MSc1; Clyde W. Yancy, MD, MSc12,13; Jonathan P. Piccini Sr, MD3

JAMA Cardiol. Published online October 26, 2022.

Importance Oral anticoagulation (OAC) is underprescribed in underrepresented racial and ethnic group individuals with atrial fibrillation (AF). Little is known of how differential OAC prescribing relates to inequities in AF outcomes.

Objective To compare OAC use at discharge and AF-related outcomes by race and ethnicity in the Get With The Guidelines–Atrial Fibrillation (GWTG-AFIB) registry.

Design, Setting, and Participants This retrospective cohort analysis used data from the GWTG-AFIB registry, a national quality improvement initiative for hospitalized patients with AF. All registry patients hospitalized with AF from 2014 to 2020 were included in the study. Data were analyzed from November 2021 to July 2022.

Exposures Self-reported race and ethnicity assessed in GWTG-AFIB registry.

Main Outcomes and Measures The primary outcome was prescription of direct-acting OAC (DOAC) or warfarin at discharge. Secondary outcomes included cumulative 1-year incidence of ischemic stroke, major bleeding, and mortality postdischarge. Outcomes adjusted for patient demographic, clinical, and socioeconomic characteristics as well as hospital factors.

Results Among 69-553 patients hospitalized with AF from 159 sites between 2014 and 2020, 863 (1.2%) were Asian, 5062 (7.3%) were Black, 4058 (5.8%) were Hispanic, and 59-570 (85.6%) were White. Overall, 34-113 (49.1%) were women; the median (IQR) age was 72 (63-80) years, and the median (IQR) CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) was 4 (2-5). At discharge, 56-385 patients (81.1%) were prescribed OAC therapy, including 41-760 (74.1%) receiving DOAC. OAC prescription at discharge was lowest in Hispanic patients (3010 [74.2%]), followed by Black patients (3935 [77.7%]) Asian patients (691 [80.1%]), and White patients (48-749 [81.8%]). Black patients were less likely than White patients to be discharged while taking any anticoagulant (adjusted odds ratio, 0.75; 95% CI, 0.68-0.84) and DOACs (adjusted odds ratio, 0.73; 95% CI, 0.65-0.82). In 16-307 individuals with 1-year follow up data, bleeding risks (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.53-2.83), stroke risks (aHR, 2.07; 95% CI, 1.34-3.20), and mortality risks (aHR, 1.22; 95% CI, 1.02-1.47) were higher in Black patients than White patients. Hispanic patients had higher stroke risk (aHR, 2.02; 95% CI, 1.38-2.95) than White patients.

Conclusions and Relevance In a national registry of hospitalized patients with AF, compared with White patients, Black patients were less likely to be discharged while taking anticoagulant therapy and DOACs in particular. Black and Hispanic patients had higher risk of stroke compared with White patients; Black patients had a higher risk of bleeding and mortality. There is an urgent need for interventions to achieve pharmacoequity in guideline-directed AF management to improve overall outcomes.