Opportunities in the Postpartum Period to Reduce Cardiovascular Disease Risk After Adverse Pregnancy Outcomes: A Scientific Statement From the American Heart Association.

Adverse pregnancy outcomes are common among pregnant individuals and are associated with long-term risk of cardiovascular disease. Individuals with adverse pregnancy outcomes also have an increased incidence of cardiovascular disease risk factors after delivery. Despite this, evidence-based approaches to managing these patients after pregnancy to reduce cardiovascular disease risk are lacking. In this scientific statement, we review the current evidence on interpregnancy and postpartum preventive strategies, blood pressure management, and lifestyle interventions for optimizing cardiovascular disease using the American Heart Association Life's Essential 8 framework. Clinical, health system, and community-level interventions can be used to engage postpartum individuals and to reach populations who experience the highest burden of adverse pregnancy outcomes and cardiovascular disease. Future trials are needed to improve screening of subclinical cardiovascular disease in individuals with a history of adverse pregnancy outcomes, before the onset of symptomatic disease. Interventions in the fourth trimester, defined as the 12 weeks after delivery, have great potential to improve cardiovascular health across the life course.

Shared Decision-Making and Cardiovascular Health: A Scientific Statement From the American Heart Association.

Shared decision-making is increasingly embraced in health care and recommended in cardiovascular guidelines. Patient involvement in health care decisions, patient-clinician communication, and models of patient-centered care are critical to improve health outcomes and to promote equity, but formal models and evaluation in cardiovascular care are nascent. Shared decision-making promotes equity by involving clinicians and patients, sharing the best available evidence, and recognizing the needs, values, and experiences of individuals and their families when faced with the task of making decisions. Broad endorsement of shared decision-making as a critical component of high-quality, value-based care has raised our awareness, although uptake in clinical practice remains suboptimal for a range of patient, clinician, and system issues. Strategies effective in promoting shared decision-making include educating clinicians on communication techniques, engaging multidisciplinary medical teams, incorporating trained decision coaches, and using tools (ie, patient decision aids) at appropriate literacy and numeracy levels to support patients in their cardiovascular decisions. This scientific statement shines a light on the limited but growing body of evidence of the impact of shared decision-making on cardiovascular outcomes and the potential of shared decision-making as a driver of health equity so that everyone has just opportunities. Multilevel solutions must align to address challenges in policies and reimbursement, system-level leadership and infrastructure, clinician training, access to decision aids, and patient engagement to fully support patients and clinicians to engage in the shared decision-making process and to drive equity and improvement in cardiovascular outcomes.

A New Era in Cardiac Rehabilitation Delivery: Research Gaps, Questions, Strategies, and Priorities.

Cardiac rehabilitation (CR) is a guideline-recommended, multidisciplinary program of exercise training, risk factor management, and psychosocial counseling for people with cardiovascular disease (CVD) that is beneficial but underused and with substantial disparities in referral, access, and participation. The emergence of new virtual and remote delivery models has the potential to improve access to and participation in CR and ultimately improve outcomes for people with CVD. Although data suggest that new delivery models for CR have safety and efficacy similar to traditional in-person CR, questions remain regarding which participants are most likely to benefit from these models, how and where such programs should be delivered, and their effect on outcomes in diverse populations. In this review, we describe important gaps in evidence, identify relevant research questions, and propose strategies for addressing them. We highlight 4 research priorities: (1) including diverse populations in all CR research; (2) leveraging implementation methodologies to enhance equitable delivery of CR; (3) clarifying which populations are most likely to benefit from virtual and remote CR; and (4) comparing traditional in-person CR with virtual and remote CR in diverse populations using multicenter studies of important clinical, psychosocial, and cost-effectiveness outcomes that are relevant to patients, caregivers, providers, health systems, and payors. By framing these important questions, we hope to advance toward a goal of delivering high-quality CR to as many people as possible to improve outcomes in those with CVD.

Psychosocial Factors Associated With Perinatal Anxiety and Perinatal Depression Among Adolescents: A Rapid Review.

The current review examined the influence of psychosocial factors on adolescents' perinatal anxiety (PA) and perinatal depression (PND) across geographical regions. Three databases were searched for articles published between 2017 and 2022 and 15 articles were reviewed. We categorized factors into social, cultural, and environmental domains. Social factors included adolescent caregiver trust/attachment, social support, perceived social support, trauma/poly-traumatization, and peer solidarity. Cultural factors included feelings of shame, marital satisfaction, partner's rejection of pregnancy, lack of parental involvement in care, parenting stress, childhood household dysfunction, and adverse childhood events. Environmental factors included neighborhood support, food insecurity, domestic violence, going to church, going out with friends, and sources for obtaining information. Routine assessment of psychosocial factors among perinatal teens is crucial to identify those at higher risk for PA and PND. Further research is necessary to examine the influence of cultural and environmental factors on PA, PND, and perinatal outcomes among adolescents. [Journal of Psychosocial Nursing and Mental Health Services, 62(2), 13-22.].

Cardio-Oncology Drug Interactions: A Scientific Statement From the American Heart Association.

In the cardio-oncology population, drug interactions are of particular importance given the complex pharmacological profile, narrow therapeutic index, and inherent risk of therapies used to manage cardiovascular disease and cancer. Drug interactions may be beneficial or detrimental to the desired therapeutic effect. Clinicians in both cardiology and oncology should be cognizant of these potential drug-drug interactions that may reduce the efficacy or safety of either cardiovascular or cancer therapies. These risks can be mitigated through increased recognition of potential drug-drug interaction, use of alternative medications when possible, and careful monitoring. This scientific statement provides clinicians with an overview of pharmacodynamic and pharmacokinetic drug-drug interactions in patients with cancer exposed to common cardiovascular and cancer medications.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

Exercise-based cardiac rehabilitation in women with heart failure: a review of enrollment, adherence, and outcomes.

Exercise-based cardiac rehabilitation (CR) is an evidence-based recommendation for patients with stable heart failure (HF). Less clear is how effective exercise-based CR is for women with HF. The aim of this review was to synthesize the evidence for the effects of exercise-based CR on mortality, hospitalizations, exercise capacity, and quality of life (QOL) among women with HF. We identified 18 studies comprising 4917 patients, of which 1714 were women. The interventions evaluated consisted of various combinations of supervised in-hospital and out-patient sessions as well as home-based programs that included aerobic (walking, treadmill, bicycle) and resistance training. The interventions ranged from 12 to 54 weeks, with a frequency of 2-7 sessions per week, lasting from 30 to 105 min per session. Because of a paucity of sex-specific analyses of the outcomes, it was not possible to draw conclusions for women. There was limited evidence for mortality benefit for men or women participating in exercise-based CR. There was more substantial evidence for reductions in hospitalizations for the participants. Generally, exercise training improved exercise capacity. The effects of exercise-based CR on QOL were mixed with most studies favoring CR at 3 months but not at 4, 5, and 12 months. Moreover, generally, the physical dimension of QOL but not the mental dimensions improved. Recommendations for future research to reduce the gap in knowledge about the effects of exercise-based CR for women are offered.

Future Perspectives of Cardiovascular Biomarker Utilization in Cancer Survivors: A Scientific Statement From the American Heart Association.

Improving cancer survival represents the most significant effect of precision medicine and personalized molecular and immunologic therapeutics. Cardiovascular health becomes henceforth a key determinant for the direction of overall outcomes after cancer. Comprehensive tissue diagnostic studies undoubtedly have been and continue to be at the core of the fight against cancer. Will a systemic approach integrating circulating blood-derived biomarkers, multimodality imaging technologies, strategic panomics, and real-time streams of digitized physiological data overcome the elusive cardiovascular tissue diagnosis in cardio-oncology? How can such a systemic approach be personalized for application in day-to-day clinical work, with diverse patient populations, cancer diagnoses, and therapies? To address such questions, this scientific statement approaches a broad definition of the biomarker concept. It summarizes the current literature on the utilization of a multitude of established cardiovascular biomarkers at the intersection with cancer. It identifies limitations and gaps of knowledge in the application of biomarkers to stratify the cardiovascular risk before cancer treatment, monitor cardiovascular health during cancer therapy, and detect latent cardiovascular damage in cancer survivors. Last, it highlights areas in biomarker discovery, validation, and clinical application for concerted efforts from funding agencies, scientists, and clinicians at the cardio-oncology nexus.

Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

A framework for addressing health inequities in sexual and gender diverse populations by nurses.

There is a need to increase health equity in sexual and gender diverse (SGD) populations, a medically underserved group with widening health disparities. To better understand and address SGD health disparities, we have developed a multi-level conceptual framework for nurse scientists that incorporates the concepts of stigma, intersectionality, identify affirmation, and life course trajectory. Social determinants of health formed the background of our conceptual framework. Using this framework, we proposed recommendations to promote SGD health equity through nursing research, health care practice, health care education, and public health care policy. These recommendations align with the National Institute of Nursing Research's goals of dismantling structures that perpetuate racism and impede health inequity and the need to implement interventions that address social determinants of health. As a result, nurse scientists are poised to influence health care policy by translating effective interventions to reduce health disparities for the SGD population into practice.

Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the American Heart Association.

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman's risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women's health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk. Notably, the 2011 American Heart Association guidelines for CVD prevention in women (the latest sex-specific guidelines to date) did not include information now available about the contribution of the MT to increased CVD in women. Therefore, there is a crucial need to discuss the contemporary literature on menopause and CVD risk with the intent of increasing awareness of the significant adverse cardiometabolic health-related changes accompanying midlife and the MT. This scientific statement provides an up-to-date synthesis of the existing data on the MT and how it relates to CVD.

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

BACKGROUND AND PURPOSE: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. METHODS: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. RESULTS: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. CONCLUSIONS: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Home-Based Cardiac Rehabilitation: A Scientific Statement From the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology.

Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program.

Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association.

Cardiovascular disease (CVD) remains the leading cause of mortality in women, yet many people perceive breast cancer to be the number one threat to women's health. CVD and breast cancer have several overlapping risk factors, such as obesity and smoking. Additionally, current breast cancer treatments can have a negative impact on cardiovascular health (eg, left ventricular dysfunction, accelerated CVD), and for women with pre-existing CVD, this might influence cancer treatment decisions by both the patient and the provider. Improvements in early detection and treatment of breast cancer have led to an increasing number of breast cancer survivors who are at risk of long-term cardiac complications from cancer treatments. For older women, CVD poses a greater mortality threat than breast cancer itself. This is the first scientific statement from the American Heart Association on CVD and breast cancer. This document will provide a comprehensive overview of the prevalence of these diseases, shared risk factors, the cardiotoxic effects of therapy, and the prevention and treatment of CVD in breast cancer patients.

Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association.

Cardiovascular disease is the leading cause of mortality in American women. Since 1984, the annual cardiovascular disease mortality rate has remained greater for women than men; however, over the last decade, there have been marked reductions in cardiovascular disease mortality in women. The dramatic decline in mortality rates for women is attributed partly to an increase in awareness, a greater focus on women and cardiovascular disease risk, and the increased application of evidence-based treatments for established coronary heart disease. This is the first scientific statement from the American Heart Association on acute myocardial infarction in women. Sex-specific differences exist in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction. This statement provides a comprehensive review of the current evidence of the clinical presentation, pathophysiology, treatment, and outcomes of women with acute myocardial infarction.

Association of Depressed Mood With Herpes Simplex Virus-2 Immunoglobulin-G Levels in Pregnancy.

OBJECTIVE: Depressed mood is common in pregnancy, is associated with stress, and could result in immune suppression that may lead to latent herpes viral reactivation. This study investigated whether depressed mood is associated with higher herpes viral IgG levels in pregnant women. METHODS: Complete cross-sectional data from 247 pregnant women were available for this substudy. The data included demographics, scores on the Perceived Stress Scale and Profile of Mood States (POMS), and a panel of serum IgG levels for human herpesviruses. RESULTS: Only the herpes simplex virus type 2 (HSV-2) (genital herpes) IgG level was associated with Perceived Stress Scale and POMS-Depression/Dejection (POMS-D) score. Hierarchical multiple regression analysis was used to examine the association of POMS-D with herpesviral IgG levels adjusting for demographic variables. In the final model, African American race (ß = .251, p < .001), older age (ß = .199, p = .002), single marital status (ß = -.304, p < .001), and depressed mood (ß = .122, p = .04) were associated with HSV-2 IgG levels. In logistic regression, the strongest correlates of HSV IgG positivity were single marital status, followed by POMS-D scores and African American race. CONCLUSION: Genital herpes is a concern in pregnancy. Antibody titers may indicate asymptomatic viral shedding, viral reactivation, or primary viral infection. Antibody levels may be higher because of the immune changes during pregnancy and potential immune effects of depressed mood causing reactivation of latent HSV-2.

Improvements in heart rate recovery among women after cardiac rehabilitation completion.

BACKGROUND: Heart rate recovery (HRR) after exercise cessation is thought to reflect the rate of reestablishment of parasympathetic tone. Relatively little research has focused on improved HRR in women after completing cardiac rehabilitation (CR) exercise training. OBJECTIVE: We examined the influence of exercise training on HRR in women completing a traditional CR program and in women completing a CR program tailored for women. METHODS: A 2-group randomized clinical trial compared HRR between 99 women completing a traditional 12-week CR program and 137 women completing a tailored CR program. Immediately upon completion of a symptom-limited graded exercise test, HRR was measured at 1 through 6 minutes. RESULTS: Compared with baseline, improvement in 1-minute HRR (HRR1) was similar (P = 0.777) between the tailored (mean [SD], 17.5 [11] to 19.1 [12]) and the traditional CR program (15.7 [9.0] to 16.9 [9.5]). The amount of change in the 2-minute HRR (HRR2) for the tailored (30 [13] to 32.8 [14.6]) and traditional programs (28.3 [12.8] to 31.2 [13.7]) also was not different (P = 0.391). Similar results were observed for HRR at 3 through 6 minutes. Given these comparable improvements of the 2 programs, in the full cohort, the factors independently predictive of post-CR HRR1, in rank order, were baseline HRR1 (part correlation, 0.35; P < 0.001); peak exercise capacity, estimated as metabolic equivalents (METs; 0.24, P < 0.001); anxiety (-0.17, P = 0.001); and age (-0.13, P = 0.016). The factors independently associated with post-CR HRR2 were baseline HRR2 (0.44, P < 0.001), peak METs (0.21, P < 0.001), and insulin use (-0.10, P = 0.041). CONCLUSIONS: One to 6 minutes after exercise cessation, HRR was significantly improved among the women completing both CR programs. The modifiable factors positively associated with HRR1 included peak METs and lower anxiety, whereas HRR2 was associated with insulin administration and peak METs. Additional research on HRR after exercise training in women is warranted.

A Mobile Health Behavior Change Intervention for Women With Coronary Heart Disease: A RANDOMIZED CONTROLLED PILOT STUDY.

PURPOSE: The aim of this study was to evaluate the effects of a mobile health (mHealth) intervention, HerBeat, compared with educational usual care (E-UC) for improving exercise capacity (EC) and other patient-reported outcomes at 3 mo among women with coronary heart disease. METHODS: Women were randomized to the HerBeat group (n = 23), a behavior change mHealth intervention with a smartphone, smartwatch, and health coach or to the E-UC group (n = 24) who received a standardized cardiac rehabilitation workbook. The primary endpoint was EC measured with the 6-min walk test (6MWT). Secondary outcomes included cardiovascular disease risk factors and psychosocial well-being. RESULTS: A total of 47 women (age 61.2 ± 9.1 yr) underwent randomization. The HerBeat group significantly improved on the 6MWT from baseline to 3 mo ( P = .016, d = .558) while the E-UC group did not ( P = .894, d =-0.030). The between-group difference of 38 m at 3 mo was not statistically significant. From baseline to 3 mo, the HerBeat group improved in anxiety ( P = .021), eating habits confidence ( P = .028), self-efficacy for managing chronic disease ( P = .001), diastolic blood pressure ( P = .03), general health perceptions ( P = .047), perceived bodily pain ( P = .02), and waist circumference ( P = .008) while the E-UC group showed no improvement on any outcomes. CONCLUSIONS: The mHealth intervention led to improvements in EC and several secondary outcomes from baseline to 3 mo while the E-UC intervention did not. A larger study is required to detect small differences between groups. The implementation and outcomes evaluation of the HerBeat intervention was feasible and acceptable with minimal attrition.

Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.