2025 AHA科学声明：当前肺栓塞的治疗和结果差异

其他心血管内科· 肺栓塞与肺动脉高压 · 2025

Mortality

A number of investigations have consistently demonstrated higher mortality rates based on race and socioeconomic status. 16, 61, 76 or example, an analysis of aggregate US population data over the past 2 decades from the CDC WONDER database (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) found that Black individuals had a nearly 2-fold increase in pulmonary heart disease-associated mortality compared with White individuals. 76 Pulmonary heart disease was defined as diseases of pulmonary circulation affecting the right side of the heart, such as pulmonary hypertension, CTEPH, and pulmonary embolism. In another evaluation of > 13 000 hospitalized patients with acute PE, Black patients had a nearly 50% higher rate of all-cause mortality compared with White patients (15.0% versus 10.7%, respectively). 61 Hispanic patients also face higher odds of in-hospital mortality compared with White men (OR, 1.34 [CI, 1.09-1.64]; P < 0.01 for Hispanic men and OR, 1.30 [CI, 1.08-1.55]; P < 0.01 for Hispanic women) based on National Inpatient Sample data. 3 cross nearly all evaluations, adverse social determinants of health and lack of access to private insurance were associated with a higher risk for in-hospital mortality. 56 In a study of 1 124 204 patients hospitalized for PE, patients with Medicare or Medicaid insurance had greater lengths of hospital stay and incurred higher hospitalization charges compared with privately insured patients, and those in the lowest income quartile had a nearly 10% absolute increase in mortality risk, even after adjusting for comorbities. 56 In an evaluation of > 53 000 Medicare fee-for-service beneficiaries, patients from socioeconomically disadvantaged populations (those dually enrolled in Medicare and Medicaid due to poverty) were more likely to be female and less likely to receive advanced therapies. 57 In addition, the 90-day readmission rate among Medicare patients from socioeconomically disadvantaged populations after a PE admission was 32.4%, compared with 24.1% among patients not from socioeconomically disadvantaged populations, which was statistically significant. Women may also have higher rates of PE-related mortality (hazard ratio, 1.24 [CI, 1.04-1.47]). 23 The exact factors and mechanistic drivers behind these observations require further elucidation. Yet, taken together, these observations confirm the need for additional investigation and strategies to mitigate disparities in acute PE outcomes.

There is evidence suggesting that rural-dwelling individuals have higher mortality rates than the urbandwelling population. Zghouzi et al 77 analyzed the CDC WONDER database and identified 109 992 PE-related deaths from 2006 through 2019. The authors found that the age-adjusted mortality rate per 100 000 was higher among patients from rural settings (OR, 4.07 [CI, 4.02-4.12]) than metropolitan areas (OR, 2.32 [CI, 2.30-2.34]). Furthermore, data show that although ageadjusted mortality rates have decreased over the years, the rate of decrease among urban-dwelling patients was 1.8% per year from 1999 through 2020, but only 1.0% per year in rural-dwelling patients. 78 Knowledge of trends in reperfusion and other management strategies of critically ill patients with PE in different regions is limited and requires more study. However, there is evidence demonstrating that rural hospitals use thrombolytics significantly less often than metropolitan hospitals (OR, 0.48 [CI, 0.43-0.52]; P < 0.01). 79 Interhospital transfer of patients with PE is not standardized as it is for myocardial infarction or stroke, and data on outcomes of patients with PE requiring transfer need further investigation.

Future Needs

# Addressing Disparities

Addressing Disparities

The population-wide disparities described in this scientific statement include those in diagnosis, treatment, outcomes, and long-term consequences of PE. Poorer outcomes seem to correlate with less health care access; reasons may include longer time to diagnosis, higher severity at presentation, longer time to initiation of anticoagulation once a PE diagnosis is made, and less access to advanced interventional and supportive care (Figure 2 ).

First, these populations need to be educated on the signs and symptoms of PE, as well as what to do if PE is suspected. Male, uninsured, low-income, and Hispanic patients are historically less aware of how cardiovascular diseases such as myocardial infarction present. 80 hus, PE educational materials should account for these populations, and be congruent with race, ethnicity, sex, and gender. Individuals with higher PE risk, such as women taking oral contraceptives, should be prioritized in receiving education. The educational materials should be disseminated in venues and through media that are frequently accessed by these groups. The health literacy of these populations needs to be considered and the readability of these materials should not be overly complex. One way of ensuring the educational content is appropriate is to evaluate and test it with patient stakeholders and content experts. 81 Other strategies, such as interactive text messaging and graphic or video media, may help overcome some health literacy and geographic challenges.

Second, health care workers who care for these populations should be educated on best practices once PE is diagnosed. For example, randomized trials have shown a < 2% mortality rate in the intermediate-highrisk PE population with prompt initiation of anticoagulation and close observation. 82 Thus, all patients with 83 Reserving IVC filtration for patients who have failed or have contraindications to anticoagulation, as stated by guidelines, is important to prevent unnecessary procedures and inconsistences in IVC filter placement. 84 Societal guidelines also recommend that high-risk patients with PE receive escalation of care with some combination of reperfusion therapy (eg, systemic thrombolysis, CDT, surgical embolectomy) and mechanical circulatory and ventilatory support. 83, 85 herefore, rural or community need to have access to adequate resources and expertise to manage non-life-threatening PE and interhospital transfer for critically ill patients requiring advanced therapies. Clear algorithms are necessary to define when and how to access these resources. Over the past decade, PE response teams have emerged to manage the challenges of severe PE, but the majority are in urban settings with academic or tertiary care hospitals. 86 Because PE is no longer considered simply an acute disease, as chronic symptoms or physiologic impairment may be present in 30% to 50% of PE survivors, 87, 88 all patients with PE should receive follow-up in the months to years after PE, to monitor their symptoms as well as intensity and duration of anticoagulation. Some populations described in this scientific statement may be at higher risk of loss to follow-up, which may account for higher rates of recurrent PE and CTEPH, and lower rates of pulmonary endarterectomy. Third, health policy should be directed toward improving public awareness and health care access. Collaborative initiatives across public health, clinical practice, and private sectors to improve public awareness of VTE are supported by the American Heart Association and may improve symptom recognition, medication adherence, and education. 89 Professional organizations can assist these efforts by establishing public health policy priorities through advocacy, creating guidelines and policy statements, and supporting scientific research to identify actionable issues. National tracking programs for PE incidence may identify broader trends in diagnosis and treatment. In addition, programs improving follow-up for rural-dwelling or low-income patients may improve longer-term outcomes in PE survivors. 90 Public policies that address income inequality may improve health equity, as evidenced by better outcomes among individuals not from socioeconomically disadvantaged populations. 91 urthermore, public health policy can improve health care access through insurance coverage, such as by incentivizing the expansion of Medicaid programs to low-income adults among states that have not already done so, which would allow for better PE follow-up care. 92 Telehealth supported by payment parity laws may improve long-term monitoring and medication compliance among patients with geographic barriers. 93 proving the Body of Knowledge Females generally constitute < 50% of participants in clinical trials of anticoagulation for VTE. 94 Furthermore, there are limited sex-specific issues reported in outcomes, such as the impact of pregnancy or hormone therapy. The largest systemic thrombolytic RCT 82 and previous CDT RCTs 95, 96 only describe sex and not race, with roughly equal numbers of males and females included. ] [99] The aforementioned studies are limited by both a lack of randomization and a small sample size, but they highlight the potential for US RCTs to enroll a considerable number of understudied populations. To capitalize on this potential, upcoming RCTs should consider inclusion of clinical trial sites with diverse populations and those in rural areas and community settings, actively recruit these populations, and include women and underrepresented physicians and patients on research leadership committees. Cohort identification should be automated, potentially using artificial intelligence or other electronic methods to identify all patients with qualifying PE who present at a trial site. 100 Trust must be established among prospective participants. Lack of trust, which might be characterized as distrust or mistrust, can affect willingness to enroll and compliance with study protocols, or influence placebo effects. 101 Participants from underrepresented racial or ethnic communities may have higher rates of mistrust in trials due to the history of mistreatment in unethical medical research. 102 Thus, the consent process should be done in a culturally sensitive manner, preferably by a team member with whom the potential participant can identify. Known cultural barriers to participation in research should be actively addressed, assuring potential participants the human subjects protection inherent in rigorous randomized trials with expansive regulatory oversight.

As described previously, race and sex disparities exist in the use of CDT and IVC filters in acute PE. White men receive both at higher rates than Black patients or females. However, neither CDT nor IVC filters has shown clear benefit in the treatment of PE. 103 In response, RCTs of CDT have been initiated by both federally funded independent investigators (PE-TRACT [Pulmonary Embolism-Thrombus Removal With Catheter-Directed Therapy; https://www.clinicaltrials.gov; unique identifier: NCT05591118]) and industry sponsors (HI-PEITHO [Ultrasound-Facilitated, Catheter-Directed, Thrombolysis in Intermediate-High-Risk Pulmonary Embolism; https://www.clinicaltrials. gov; unique identifier: NCT04790370] and PEERLESS II [PEERLESS II: RCT of FlowTriever vs Anticoagulation Alone in Pulmonary Embolism; https://www.clinicaltrials.gov; unique identifier: NCT06055920]). These trials represent an opportunity to improve knowledge of understudied populations.

Once underrepresented patients enter trials, all means to retain them in the study should be used, including automated reminders, close follow-up, and strong communication between the participant and study team. If these measures are achieved, meaningful subgroup analyses may be conducted that will illuminate both the presentation and natural history of PE in these populations as well as their responses to therapy. If necessary, further funding to study these data should be sought. Any signals identified in subgroup analyses should be followed with additional rigorous, hypothesis-driven trials.

CONCLUSION

PE affects individuals from all backgrounds. Race, ethnicity, sex, gender, and socioeconomic status influence all aspects of PE, from incidence to diagnosis, treatment, and outcomes. The available data show that women, transfeminine individuals, patients from underrepresented racial or ethnic groups, and patients from socioeconomically disadvantaged populations experience higher rates of PE with less access to timely imaging and therapeutic interventions. These groups bear a disproportionate burden of morbidity and mortality.

Addressing the disparities related to PE management represents a formidable challenge. Recognizing the issues and appreciating the pervasiveness of differences in health care delivery is the first step to ensuring equitable care for all patients. Monitoring these issues over time with new data can help elucidate trends and inform clinical practices. Making equitable care a reality will require collaborative efforts from all stakeholders involved in PE management. Furthermore, deliberate emphasis on inclusivity in research will ensure that data will be more representative and help close knowledge gaps on the impact of race, sex, and other important social factors on PE management.

Race refers to the classification of people by physical or biologic traits, such as skin color (eg, Black, White, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islander), whereas ethnicity characterizes people on the basis of cultural identification, such as common history and language (eg, Hispanic). Racial and ethnic differences in the incidence and outcomes of PE in the United States are welldocumented. ] [8] [9] [10] [11] [12] [13] A study by Martin and colleagues 14 analyzing the Illinois Health and Hospital Association's Comparative Health Care and Hospital Data Reporting Services found that Black patients were 1.9 times more likely to be hospitalized for PE than White patients after adjusting for age and sex. A study of 545 343 fee-for-service Medicare beneficiaries age 65 years or older from 1999 to 2010 showed a higher rate of hospitalization and mortality for Black individuals compared with people from other racial groups. 15 These mortality differences may be associated with factors such as insurance status, as well as immediate and longitudinal access to medical care, including access to centers of excellence. 7 ispanic patients have a lower incidence of venous thromboembolism (VTE) compared with non-Hispanic White patients, but a higher incidence than Asian patients and Pacific Islander patients. 13 However, 1 single-center study found that despite presenting with lower PE severity and lower rates of PE-specific intervention, Hispanic patients had similar in-hospital all-cause and PE-related mortality rates compared with non-Hispanic patients. 16 Studies of Asian individuals are more limited and have smaller sample sizes. Available data suggest that Asian individuals have low VTE risk, although an explanation for this lower incidence rate remains unclear. 17, 18 The limited studies of Native American or Alaskan native populations have also found a lower incidence of PE compared with Black populations or White populations.

Sex and Gender Considerations

Pediatric PE

ARTICLE INFORMATION

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on December 3, 2024, and the American Heart Association Executive Committee on January 16, 2025. A copy of the document is available at https://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com

The American Heart Association requests that this document be cited as follows: Takahashi Permissions: Multiple copies, modification, alteration, enhancement, and distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the "Copyright Permissions Request Form" appears in the second paragraph (https://www.heart.org/en/about-us/ statements-and-policies/copyright-request-form).

Disclosures

Outside the submitted work, Dr Bikdeli is supported by a Heart and Vascular Center Junior Faculty Award from Brigham and Women's Hospital; is a member of the Medical Advisory Board for the North American Thrombosis Forum and serves on the Data Safety and Monitoring Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute and Translational Sciences; is a collaborating consultant with the International Consulting Associates and the US Food and Drug Administration in a study to generate knowledge about utilization, predictors, retrieval, and safety of IVC filters; receives compensation as an Associated Editor for the New England Journal of Medicine Journal Watch Cardiology, as an Associate Editor for Thrombosis Research, and as an Executive Associate Editor for JACC; and is a Section Editor for Thrombosis and Haemostasis (no compensation). Dr Addison is supported by the National Institutes of Health (grants K23-HL155890, R01HL168045, and R01HL170038) and an American Heart Association-Robert Wood Johnson Foundation (Harold Amos) grant. Dr Addison receives compensation as an Associated Editor for JACC: Cardiovascular Imaging. Dr Sista is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (award UH3HL155798). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Uniformed Services University of the Health Sciences or the Department of Defense of the United States of America. This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives ≥$5000 during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns ≥$5000 of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition. *Modest. †Significant. This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives ≥$5000 during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns ≥$5000 of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition. *Modest. †Significant.

|Factors|Disparities in management Disparities in outcomes|| |---|---|---|

|Race and|Black patients may be offered|Black patients have|

|ethnicity 3,55,58,61|direct oral anticoagulation|higher rates of CTEPH;|

||less frequently than White|Black and Hispanic|

||patients; underrepresented|patients have higher|

||racial and ethnic patients|mortality and hospital|

||are less likely to undergo ad-|readmission rates than|

||vanced therapies for PE|White patients|

|Sex 3,50,59,60|Females undergo more|Females have more|

||low-yield CT scans to rule|bleeding complications|

||out PE and fewer advanced|from anticoagulation as|

||PE therapies, such as|well as higher CTEPH|

||thrombectomy|rates than men|

|Socioeconomic|Patients with lower SES|Patients with lower SES|

|status 3,46,56,57|have reduced access to|have higher PE-related|

||high-quality imaging centers|readmission rates and|

||and undergo fewer|mortality risk compared|

||advanced interventions|with affluent patients|

References

EN_PAPER

Disparities in Current Pulmonary Embolism Management and Outcomes: A Scientific Statement From the American Heart Association

Authors

Abstract

Pulmonary embolism is a common cause of cardiovascular-associated morbidity and mortality. Although pulmonary embolism affects individuals from all demographics, the incidence of pulmonary embolism is higher among people from certain racial groups, reproductive-age women compared with age-matched men, and transgender people taking estrogen hormones. Furthermore, disparities may exist in the diagnosis or management strategies of pulmonary embolism associated with race, ethnicity, sex, or socioeconomic status, which may correlate with poorer downstream outcomes, including recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, or short-or long-term mortality. This scientific statement summarizes disparities in diagnosis, treatment strategies, and outcomes related to pulmonary embolism, and reviews approaches to create equitable pulmonary embolism care and address the knowledge gaps in the literature.

METHODS

A diverse group of experts involved in research and clinical care of patients with PE was convened. For reporting the incidence, epidemiology, or prognostication, where available, studies with detailed clinical information (such as representative large prospective cohort studies) were prioritized. If not available, regional or single-center studies using high-quality patient-level data collection were considered, recognizing that external validity may be limited. Large-scale studies using administrative claims data (ie, International Classification of Diseases codes) were considered, particularly if they used a validated reliable method for identification of patients or the outcome variable. 4, 5 For comparative effectiveness or safety questions, randomized controlled trials (RCTs) and rigorously conducted pooled analyses of trials were prioritized. If RCTs were not available, prospective controlled TBD TBD, 2025

Circulation. 2025;151:e00-e00. DOI: 10.1161/CIR.0000000000001306 e2 Takahashi et al Disparities in Pulmonary Embolism Management and Outcomes observational studies were considered, recognizing that causal inference would be limited with such studies or other designs.

Racial and Ethnic Considerations

Biologic sex (female or male) and sociocultural factors related to gender (woman, man, or nonbinary) may correlate with the incidence of PE, how PE symptoms are perceived and reported, and how pharmacologic and nonpharmacologic therapies are being delivered. 20 Females of reproductive age have a higher risk of PE compared with males. 20, 21 Recent epidemiologic data, contrary to previous estimates, 21 suggest that even among older adults (≥65 years), identified cases of PE are more frequently found in females than in males. 5, 22 Regarding presentation, dyspnea is the most common initial PE symptom in both sexes, but chest pain and hemoptysis are slightly less common in females. 5, 20 In some studies, females were more likely to have severe symptoms, such as hypotension, hypoxemia, and right heart strain at presentation. 23 hereas several PE risk factors, such as major surgery or trauma, may occur similarly for females and males, others, such as a hyperestrogenic state because of oral contraceptive use, pregnancy, or hormone replacement therapy, are almost exclusive to females. Other risk factors for VTE are more common in females, such as varicose veins or May-Thurner physiology. 24, 25 Enduring risk factors, such as malignancy, particularly lung cancer, and cardiovascular disease, are more commonly found in males, whereas rheumatologic diseases and depression are more frequent in females. 5 ex-related differences may also exist because of the influence of biologic sex on choice of therapies by clinicians or patients, differences in access to optimal care, or implicit or explicit biases within the health care system. For example, heavy menstrual bleeding may affect patients' adherence to or informed choices for the duration of anticoagulation. 26 stablishing PE risk assessments among transgender and gender-diverse individuals is challenging due to widely variable hormonal therapies and the paucity of high-quality studies investigating the presentation, therapies, or outcomes of these individuals. 27 Genderaffirming hormone therapy is a key part of a transgender or gender-diverse individual's treatment path. For transfeminine individuals (people who identify as women but were assigned male at birth), the specific hormone regimen is particularly important. 28 0] [31] The risk of PE and other thromboembolic events is higher in transfeminine individuals who have been taking estrogens, 32, 33 particularly oral ethinyl estradiol. 34 The risk is especially high during the first year of taking the supraphysiologic-level regimens of feminizing hormones. 35 Transfeminine individuals taking hormones increase their risk further when they have other risk factors. such as smoking, obesity, or a history of thrombosis. 27, 29, 32, 36 More research is crucial to better understand the effects of hormone therapy on VTE risk among the transgender population and to determine incidence rates, optimal management strategies, and outcomes.

引用 / 出处

2025 AHA科学声明：当前肺栓塞的治疗和结果差异. 2025.