Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry.

BACKGROUND: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. METHODS: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. RESULTS: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). CONCLUSION: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

A large, multi-center survey assessing health, social support, literacy, and self-management resources in patients with heart failure.

BACKGROUND: Most patients with heart failure (HF) have multimorbidity which may cause difficulties with self-management. Understanding the resources patients draw upon to effectively manage their health is fundamental to designing new practice models to improve outcomes in HF. We describe the rationale, conceptual framework, and implementation of a multi-center survey of HF patients, characterize differences between responders and non-responders, and summarize patient characteristics and responses to the survey constructs among responders. METHODS: This was a multi-center cross-sectional survey study with linked electronic health record (EHR) data. Our survey was guided by the Chronic Care Model to understand the distribution of patient-centric factors, including health literacy, social support, self-management, and functional and mental status in patients with HF. Most questions were from existing validated questionnaires. The survey was administered to HF patients aged ≥ 30 years from 4 health systems in PCORnet® (the National Patient-Centered Clinical Research Network): Essentia Health, Intermountain Health, Mayo Clinic, and The Ohio State University. Each health system mapped their EHR data to a standardized PCORnet Common Data Model, which was used to extract demographic and clinical data on survey responders and non-responders. RESULTS: Across the 4 sites, 10,662 patients with HF were invited to participate, and 3330 completed the survey (response rate: 31%). Responders were older (74 vs. 71 years; standardized difference (95% CI): 0.18 (0.13, 0.22)), less racially diverse (3% vs. 12% non-White; standardized difference (95% CI): -0.32 (-0.36, -0.28)), and had higher prevalence of many chronic conditions than non-responders, and thus may not be representative of all HF patients. The internal reliability of the validated questionnaires in our survey was good (range of Cronbach's alpha: 0.50-0.96). Responders reported their health was generally good or fair, they frequently had cardiovascular comorbidities, > 50% had difficulty climbing stairs, and > 10% reported difficulties with bathing, preparing meals, and using transportation. Nearly 80% of patients had family or friends sit with them during a doctor visit, and 54% managed their health by themselves. Patients reported generally low perceived support for self-management related to exercise and diet. CONCLUSIONS: More than half of patients with HF managed their health by themselves. Increased understanding of self-management resources may guide the development of interventions to improve HF outcomes.

Comparison of the effectiveness and safety of 2 aspirin doses in secondary prevention of cardiovascular outcomes in patients with chronic kidney disease: A subgroup analysis of ADAPTABLE.

BACKGROUND: Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD). METHODS: ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups. RESULTS: After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P = .95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P = .79) between ASA groups. CONCLUSIONS: Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD.

Outcomes of same-day discharge following percutaneous coronary intervention in a rural population.

BACKGROUND: Same-day discharge (SDD) following percutaneous coronary intervention (PCI) is safe, yet the nationwide rate of SDD remains low. The impact that residing in a rural area has on the safety of SDD is unknown. OBJECTIVE: To investigate the safety of SDD compared to next-day discharge (NDD) among PCI patients living in a largely rural area. METHODS: There were 3502 outpatient elective PCIs at a tertiary care center between January 1, 2011 and December 31, 2017. Data from the National Cardiovascular Data Registry CathPCI Registry® and the electronic medical records were obtained for patient demographics, procedural characteristics, and procedural outcomes. Data from the initial PCI in each 365-day period were included in the analysis for each patient. Rural-Urban Commuting Area codes 4-10 were used to define rural status. RESULTS: A total of 2099 (59.9%) PCIs met the inclusion criteria (63% rural). The overall rate of SDD increased over time (4.7% in 2011 to 39.6% in 2017) as radial access increased (14.2% in 2011 to 59.9% in 2017). In this population, a total of 329 PCIs had SDD (15.7%; median (interquartile range) age 66.0 (14.0) years, 20.1% female, 52.3% rural status). Compared to NDD, SDD patients had less hyperlipidemia, atrial fibrillation, congestive heart failure, history of coronary artery bypass graft, and more radial access. SDD was noninferior to NDD for 30-day readmission but had a decreased 1-year (adjusted odds ratio [aOR]: 0.20, 95% confidence interval [CI]: 0.05-0.81, p = 0.024) and 5-year (aOR: 0.43, 95% CI: 0.28-0.66, p < 0.001) all-cause mortality compared to NDD. Rural status did not predict outcomes. CONCLUSIONS: SDD in patients in rural areas does not have a significantly higher rate of 30-day readmission. SDD patients had lower odds of 1- and 5-year mortality when compared to NDD. Future studies prospectively evaluating the safety of SDD in this population are warranted.

Outcomes among patients with peripheral artery disease in the Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) study.

BACKGROUND: We aimed to understand the effects of aspirin dose on outcomes in patients with peripheral artery disease (PAD) as well as their participation in a pragmatic randomized controlled trial. METHODS: In a subanalysis of the Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) study, we compared aspirin doses (81 vs 325 mg) among participants with PAD and study participation metrics in patients with and without PAD. The primary outcome composite was all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: Among 14,662 participants enrolled in ADAPTABLE with PAD status available, 3493 (23.8%) had PAD. Participants with PAD were more likely to experience the primary composite (13.76% vs 5.31%, p < 0.001), all-cause mortality (7.55% vs 3.01%, p < 0.001), myocardial infarction (5.71% vs 2.09%, p < 0.001), stroke (2.45% vs 0.86%, p < 0.001), and major bleeding (1.19% vs 0.44%, p < 0.001). A higher aspirin dose did not reduce the primary outcome in patients with PAD (13.68% vs 13.84% in 81 mg and 325 mg groups; OR 1.05, 95% CI 0.88-1.25). Participants with PAD were less likely to enroll via email (33.0% vs 41.9%, p < 0.0001), less likely to choose internet follow-up (79.2% vs 89.5%, p < 0.0001), and were more likely to change their aspirin doses (39.7% vs 30.7%, p < 0.0001). CONCLUSIONS: ADAPTABLE participants with PAD did not benefit from a higher dose of aspirin and participated in the study differently from those without PAD. These results reinforce the need for additional PAD-specific research and suggest that different trial strategies may be needed for optimal engagement of patients with PAD. (ClinicalTrials.gov Identifier: NCT02697916).

Achieving Optimal Population Cardiovascular Health Requires an Interdisciplinary Team and a Learning Healthcare System: A Scientific Statement From the American Heart Association.

Population cardiovascular health, or improving cardiovascular health among patients and the population at large, requires a redoubling of primordial and primary prevention efforts as declines in cardiovascular disease mortality have decelerated over the past decade. Great potential exists for healthcare systems-based approaches to aid in reversing these trends. A learning healthcare system, in which population cardiovascular health metrics are measured, evaluated, intervened on, and re-evaluated, can serve as a model for developing the evidence base for developing, deploying, and disseminating interventions. This scientific statement on optimizing population cardiovascular health summarizes the current evidence for such an approach; reviews contemporary sources for relevant performance and clinical metrics; highlights the role of implementation science strategies; and advocates for an interdisciplinary team approach to enhance the impact of this work.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Clinician engagement in the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) trial.

BACKGROUND: ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) is a pragmatic clinical trial examining high-dose versus low-dose aspirin among patients with cardiovascular disease. ADAPTABLE is leveraging novel approaches for clinical trial conduct to expedite study completion and reduce costs. One pivotal aspect of the trial conduct is maximizing clinician engagement. METHODS/RESULTS: Clinician engagement can be diminished by barriers including time limitations, insufficient research infrastructure, lack of research training, inadequate compensation for research activities, and clinician beliefs. We used several key approaches to boost clinician engagement such as empowering clinician champions, including a variety of clinicians, nurses and advanced practice providers, periodic newsletters and coordinated team celebrations, and deploying novel technological solutions. Specifically, some centers generated electronic health records-based best practice advisories and research dashboards. Future large pragmatic trials will benefit from standardization of the various clinician engagement strategies especially studies leveraging electronic health records-based approaches like research dashboards. Financial or academic "credit" for clinician engagement in clinical research may boost participation rates in clinical studies. CONCLUSION: Maximizing clinician engagement is important for the success of clinical trials; the strategies employed in the ADAPTABLE trial may serve as a template for future pragmatic studies.

Projected growth of the adult congenital heart disease population in the United States to 2050: an integrative systems modeling approach.

BACKGROUND: Mortality for children with congenital heart disease (CHD) has declined with improved surgical techniques and neonatal screening; however, as these patients live longer, accurate estimates of the prevalence of adults with CHD are lacking. METHODS: To determine the prevalence and mortality trends of adults with CHD, we combined National Vital Statistics System data and National Health Interview Survey data using an integrative systems model to determine the prevalence of recalled CHD as a function of age, sex, and year (by recalled CHD, we mean positive response to the question "has a doctor told you that (name) has congenital heart disease?", which is a conservative lower-bound estimate of CHD prevalence). We used Human Mortality Database estimates and US Census Department projections of the US population to calculate the CHD-prevalent population by age, sex, and year. The primary outcome was prevalence of recalled CHD in adults from 1970 to 2050; the secondary outcomes were birth prevalence and mortality rates by sex and women of childbearing age (15-49 years). RESULTS: The birth prevalence of recalled CHD in 2010 for males was 3.29 per 1,000 (95 % uncertainty interval (UI) 2.8-3.6), and for females was 3.23 per 1,000 (95 % UI 2.3-3.6). From 1968 to 2010, mortality among zero to 51-week-olds declined from 170 to 53 per 100,000 person years. The estimated number of adults (age 20-64 years) with recalled CHD in 1968 was 118,000 (95 % UI 72,000-150,000). By 2010, there was an increase by a factor of 2.3 (95 % UI 2.2-2.6), to 273,000 (95 % UI 190,000-330,000). There will be an estimated 510,000 (95 % UI: 400,000-580,000) in 2050. The prevalence of adults with recalled CHD will begin to plateau around the year 2050. In 2010, there were 134,000 (95 % UI 69,000-160,000) reproductive-age females (age 15-49 years) with recalled CHD in the United States. CONCLUSION: Mortality rates have decreased in infants and the prevalence of adults with CHD has increased but will slow down around 2050. This population requires adult medical systems with providers experienced in the care of adult CHD patients, including those familiar with reproduction in women with CHD.

The effect of changes in visibility and price on fruit purchasing at a university cafeteria in Lima, Peru.

OBJECTIVE: To determine the effect of increasing fruit visibility, adding information and lowering price on fruit purchasing at a university cafeteria in Lima, Peru. DESIGN: Quasi-experimental pilot study of a three-phase stepped intervention. In Phase 1, fruit was displayed >3 m from the point of purchase with no additional information. Phase 2 consisted in displaying the fruit near the point of purchase with added health and price information. Phase 3 added a 33% price reduction. The duration of each phase was 3 weeks and phases were separated by 2-week breaks. Primary outcomes were total pieces of fruit and number of meals sold daily. SETTING: A university cafeteria in Lima, Peru. SUBJECTS: Approximately 150 people, students and non-student adults, who purchased food daily. Twelve students participated in post-intervention interviews. RESULTS: Fruit purchasing doubled from Phase 1 to Phase 3 (P<0·01) and remained significant after adjusting for the number of meals sold daily (P<0·05). There was no evidence of a difference in fruit sold between the other phases. Females purchased 100% of the fruit in Phase 1, 82% in Phase 2 and 67% in Phase 3 (P<0·01). Males increased their purchasing significantly between Phase 1 and 3 (P<0·01). Non-student adults purchased more fruit with each phase (P<0·05) whereas students did not. Qualitatively, the most common reason for not purchasing fruit was a marked preference to buy unhealthy snack foods. CONCLUSIONS: Promoting fruit consumption by product placement close to the point of purchase, adding health information and price reduction had a positive effect on fruit purchasing in a university cafeteria, especially in males and non-student adults.

The Impact of Stimulant Medications on Blood Pressure and Body Mass Index in Children with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: To describe changes in blood pressure (BP) and body mass index (BMI) associated with stimulant medication fills in children. METHODS: Observational, retrospective matched cohort study of children 6-17.9 years initiating stimulant medication between 7/1/2010-6/30/2017 matched 1:3 by age, race, ethnicity, and sex to children with no stimulant use during this period. All BPs and BMIs recorded during ambulatory visits were identified. Generalized linear models were used to estimate differences in change in systolic BP (SBP), diastolic BP (DBP), and BMI over time. RESULTS: The 686 children with stimulant prescription fills and 2048 matched controls did not differ by baseline SBP or BMI. The matched control group (30.5% female, mean age 11.2 ± 3.4 years 79.7% white) was more likely to be publicly insured (35% vs. 21%, P < .01). After adjusting for baseline values, over a mean follow-up of 144 days change in SBP or DBP did not differ significantly between patients with stimulant medication fills and matched controls. Stimulant use was associated with a 4.7 percentile decrease in BMI percentile compared to matched controls (95% CI: 3.69, 5.71; P < .01). CONCLUSIONS: In a pediatric primary care cohort, stimulant prescription fills were associated with marked decreases in BMI but no significant changes in BP over time.

The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: A multi-site study.

BACKGROUND: Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health-related quality of life in patients with HF is not well understood. METHODS: Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF-related prescription drugs from four U.S. institutions were mailed a survey to measure patient-centric factors including functional status (activities of daily living [ADLs]) and health-related quality of life (PROMIS-29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non-cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS-29 sub-scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. RESULTS: A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66-4.45), depression (OR: 3.11, 95% CI: 2.39-4.06), and fatigue (OR: 4.19, 95% CI: 3.25-5.40); worse sleep (OR: 2.14, 95% CI: 1.69-2.72) and pain (OR: 6.73, 95% CI: 5.15-8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19-12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. CONCLUSION: Patients with only functional limitation have similar poor health-related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well-being of patients with HF.

Impact of aspirin dose according to race in secondary prevention of atherosclerotic cardiovascular disease: a secondary analysis of the ADAPTABLE randomised controlled trial.

OBJECTIVES: To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD). DESIGN: A secondary analysis of the randomised controlled trial ADAPTABLE was performed. SETTING: The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA. PARTICIPANTS: Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%). INTERVENTIONS: Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion. RESULTS: Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints. CONCLUSION: Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race. TRIAL REGISTRATION NUMBER: NCT02697916.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses. Objective: To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial. Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024. Interventions: Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD. Main Outcomes and Measures: The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion. Results: A total of 15 076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10 352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence. Conclusions and Relevance: In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

Contribution of Clinical Trial Event Data by Data Source: A Prespecified Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Pragmatic randomized clinical trials (RCTs) often use multiple data sources to examine clinical events, but the relative contribution of data sources to clinical end-point rates is understudied. Objective: To assess the contribution of data sources (electronic health records [EHRs], public/private insurance claims, and/or participant-reported data) to clinical end points among ADAPTABLE participants who had available data. Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic RCT from April 2016 through June 2019 conducted in research networks within clinical practice. Participants had existing atherosclerotic cardiovascular disease and available data to analyze. The characteristics of patients by combinations of data source availability were compared to examine the contribution of each of the data sources to end-point ascertainment. Data for this prespecified analysis were examined from January 2022 to June 2023. Exposures: Randomized exposure to 81 mg or 325 mg of aspirin daily. Main Outcomes and Measures: Number of events for the primary end point (composite of death, hospitalization for myocardial infarction, and hospitalization for stroke) that were contributed by EHR or claims data and then number of events contributed by each additional data source. Results: Of 15 006 participants randomized with at least 1 other source of data available beyond participant-reported data, there were 8756 (58.3%) with participant-reported and EHR data; 4291 (28.6%) with participant-reported, EHR, and claims data; 1412 (9.4%) with EHR-only data; 262 (1.7%) with participant-reported and claims data; 202 (1.3%) with EHR and claims data; and 83 (0.6%) with claims-only data. Participants with EHR-only data were younger (median age, 63.7 years; IQR, 55.8-71.4) compared with the other groups (range, 65.6-71.9 years). Among participants with both EHR and claims data, with or without participant-reported data (n = 4493), for each outcome, most events (92%-100%) were identified in the EHR or in claims data. For all clinical end points, participant-reported data contributed less than 10% of events not otherwise available from claims or EHR data. Conclusions and Relevance: In this analysis of a pragmatic RCT, claims and EHR data provided the most clinical end-point data when compared with participant-reported events. These findings provide a framework for collecting end points in pragmatic clinical trials. Further work is needed to understand the data source combinations that most effectively provide clinical end-point data in RCTs.

Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Adapting a clinical decision support system to improve identification of pediatric hypertension in a rural health system: Design of a pragmatic trial.

BACKGROUND: Identifying hypertension (HTN) early is crucial in preventing and lowering the long-term risk of heart disease, yet HTN in children often goes undiagnosed. An electronic health record linked, web-based clinical decision support (CDS) called PedsBP can help address this care gap and has been previously shown to increase recognition of HTN by primary care clinicians. OBJECTIVES: To adapt the PedsBP tool for use in a mostly rural health system and then to evaluate the effectiveness of PedsBP for repeat of hypertensive level blood pressure (BP) measurements and HTN recognition among youth 6-17 years of age in primary care settings, comparing low-intensity and high-intensity implementation approaches. METHODS AND DESIGN: PedsBP was evaluated through a pragmatic, clinic-randomized trial. The tool was piloted in 2 primary care clinics and modified prior to the full trial. Forty community-based, primary care clinics (or clusters of clinics) were randomly allocated in a 1:1:1 ratio to usual care, low-intensity implementation (CDS only), or high-intensity implementation (CDS plus in-person training, monthly use reports, and ongoing communication between study staff and clinics). Accrual of eligible patients started on August 1, 2022 and will continue for 18 months. Primary outcomes include repeating hypertensive level BP measurements at office visits and clinical recognition of HTN. Secondary outcomes include lifestyle counseling, dietician referral, and BP at follow-up. CONCLUSION: This report focuses on the design and feasibility of adapting and implementing PedsBP in a rural primary care setting. The trial and analysis are ongoing with main results expected in mid-2024.

Internet Versus Noninternet Participation in a Decentralized Clinical Trial: Lessons From the ADAPTABLE Study.

Background Internet-based participation has the potential to enhance pragmatic and decentralized trials, where representative study populations and generalizability to clinical practice are key. We aimed to study the differences between internet and noninternet/telephone participants in a large remote, pragmatic trial. Methods and Results In a subanalysis of the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) study, we compared internet participants with those who opted for noninternet participation. Study process measures examined included participant characteristics at consent, study medication adherence, and study retention. The clinical outcome examined was a composite of all-cause mortality, hospitalization for myocardial infarction, or hospitalization for stroke. Noninternet participants were older (mean 69.4 versus 67.4 years), more likely to be female (38.9% versus 30.2%), more likely to be Black (27.3% versus 6.0%) or Hispanic (11.1% versus 2.0%), and had a higher number of comorbid conditions. The composite clinical outcome was more than twice as high in noninternet participants. The hazard of nonadherence to the assigned aspirin dosage was 46% higher in noninternet participants than internet participants. Conclusions Noninternet participants differed from internet participants in notable demographic characteristics while having poorer baseline health. Over the course of ADAPTABLE, they also had worse clinical outcomes and greater likelihood of study drug nonadherence. These results suggest that trials focused on internet participation select for younger, healthier participants with a higher proportion of traditionally overrepresented patients. Allowing noninternet participation enhances diversity; however, additional steps may be needed to promote study retention and study medication adherence. Registration Information clinicaltrials.gov. Identifier: NCT02697916.