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.

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.

Trends of Hospitalizations and In-Hospital Outcomes for Traumatic Cardiac Injury in United States.

Introduction: Traumatic cardiac injury (TCI) poses a significant risk of morbidity and mortality, yet there is a lack of population-based outcomes data for these patients. Methods: The authors examined national yearly trends, demographics, and in-hospital outcomes of TCI using the National Inpatient Sample from 2007 to 2014. We focused on adult patients with a primary discharge diagnosis of TCI, categorizing them into blunt (BTCI) and penetrating (PTCI) cardiac injury. Results: A total of 11,510 cases of TCI were identified, with 7,155 (62.2%) classified as BTCI and 4,355 (37.8%) as PTCI. BTCI was predominantly caused by motor vehicle collisions (66.7%), while PTCI was mostly caused by piercing injuries (67.4%). The overall mortality rate was 11.3%, significantly higher in PTCI compared to BTCI (20.3% vs. 5.9%, χ2(1, N = 11,185) = 94.9, p <0.001). Additionally, 21.5% required blood transfusion, 19.6% developed hemopericardium, and 15.9% suffered from respiratory failure. Procedures such as heart and pericardial repair were more common in PTCI patients. Length of hospitalization and cost of care were also significantly higher for PTCI patients, W(1, N = 11,015) = 88.9, p <0.001). Conclusions: Patients with PTCI experienced higher mortality rates than those with BTCI. Within the PTCI group, young men from minority racial groups and low-income households had poorer outcomes. This highlights the need for early and specialized attention from emergency and cardiothoracic providers for patients in these demographic groups.

High ankle-brachial index participants experienced similar long-term mortality as peripheral artery disease in a national sample of community-dwelling adults.

BACKGROUND: Only a few small studies have shown the association between high ankle-brachial pressure index (ABI >1.4) and adverse cardiovascular (CV) events and mortality. Although there is abundant literature depicting the association between ABI and overall systemic atherosclerosis, it typically focuses on low ABI. Furthermore, historically, many studies focusing on peripheral artery disease have excluded high ABI participants. We aimed to study the mortality outcomes of persons with high ABI in the National Health and Nutrition Examination Survey (NHANES). METHODS: We obtained ABI from participants aged ≥40 years for survey years 1999 to 2004. We defined low a ABI as ≤0.9, normal ABI as 0.9 to 1.4, and high ABI as >1.4 or if the ankle pressures were >245 mm Hg. Demographics, various comorbidities, and laboratory test results were obtained at the time of the survey interview. Multivariable adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs) were calculated for CV and all-cause mortality via Cox proportional hazards regression. Mortality was linked to all NHANES participants for follow-up through December 31, 2019, by the Centers for Disease Control and Prevention. RESULTS: We identified 7639 NHANES participants with available ABI. Of these, 6787 (89%) had a normal ABI, 646 (8%) had a low ABI, and 206 (3%) had elevated ABI. Of participants with high ABI, 50% were men, 15% were African Americans, 10% were current smokers, 56% had hypertension, 33% had diabetes, 15% had chronic kidney disease (CKD), and 18% had concomitant coronary artery disease (CAD). Diabetes (odds ratio [OR], 2.4; 95% CI, 1.7-3.2), CAD (OR, 1.6; 95% CI, 1.0-2.4), and CKD (OR, 1.5; 95% CI, 1.0-2.3) at baseline were associated with having a high ABI, respectively. A high ABI was associated independently with elevated CV (HR, 2.6; 95% CI, 2.1-3.1; P < .0001) and all-cause mortality (HR, 2.5; 95% CI, 2.2-2.8; P < .0001) after adjusting for covariates, including diabetes, CKD, CAD, current smoking, cancer, and hypertension. CONCLUSIONS: A high ABI is associated with an elevated CV and all-cause mortality, similar to patients with PAD. High ABI participants should receive the same attention and aggressive medical therapies as patients with PAD.

Nationwide Trends and Outcomes for Coronary Artery Bypass Grafting in End-Stage Kidney Disease and Stable Coronary Artery Disease.

Patients with end-stage kidney disease (ESKD) on dialysis have an increased burden of coronary artery disease (CAD). This study assessed the trend and outcomes for coronary artery bypass surgery (CABG) in patients with ESKD and stable CAD. We conducted a longitudinal study using the United States Renal Data System of patients with ESKD and stable CAD who underwent CABG from the years 2009 to 2017. The outcomes included in-hospital, long-term mortality, and repeat revascularization. The follow-up was until death, end of Medicare AB coverage, or December 31, 2018. A total of 11,952 patients were identified. The mean age was 62.8 years, 68% were male, and 67% were white. The common co-morbidities included hypertension (97%), diabetes mellitus (75%), and congestive heart failure (53%). A significant decrease in CABG procedures from 2.9 to 1.3 procedures per 1,000 patients with ESKD (p <0.001) was noted during the years studied. The overall in-hospital mortality rate was 5.9%, and there was a significant decrease over the study period (p = 0.01). Although the 30-day mortality rate was 6.9% and remained steady (p = 0.14), the 1-year mortality rate was 22.8% and decreased significantly (p <0.001). At 5 years, the overall survival rate was 35%, and patients with internal mammary artery grafts showed better survival than those without (36% vs 25%). In conclusion, there has been a decrease in CABG procedures performed in patients with ESKD with stable CAD with decreasing in-hospital and 1-year mortality. Those with an internal mammary artery graft do better, but the overall long-term survival remains dismal in this population. There remains need for caution and individualization of revascularization decisions in this high-risk population.

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.

Outcomes of peripheral artery disease and polyvascular disease in patients with end-stage kidney disease.

OBJECTIVE: Patients with peripheral artery disease (PAD) and end-stage kidney disease are a high-risk population, and concomitant atherosclerosis in coronary arteries (CAD) or cerebral arteries (CVD) is common. The aim of the study was to assess long-term outcomes of PAD and the impact of coexistent CAD and CVD on outcomes. METHODS: The United States Renal Data System was used to identify patients with PAD within 6 months of incident dialysis. Four groups were formed: PAD alone, PAD with CAD, PAD with CVD, and PAD with CAD and CVD. PAD-specific outcomes (chronic limb-threatening ischemia, major amputation, percutaneous/surgical revascularization, and their composite, defined as major adverse limb events [MALE]) as well as all-cause mortality, myocardial infarction, and stroke were studied. RESULTS: The study included 106,567 patients (mean age, 71.2 years; 40.8% female) with a median follow-up of 546 days (interquartile range, 214-1096 days). Most patients had PAD and CAD (49.8%), 25.8% had PAD alone, and 19.2% had all three territories involved. MALE rate in patients with PAD was 22.3% and 35.0% at 1 and 3 years, respectively. In comparison to PAD alone, the coexistence of both CAD and CVD (ie, polyvascular disease) was associated with a higher adjusted rates of all-cause mortality (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.24-1.31), myocardial infarction (HR, 1.78; 95% CI, 1.69-1.88), stroke (HR, 1.66; 95% CI, 1.52,1.80), and MALE (HR, 1.07; 95% CI, 1.04-1.11). CONCLUSIONS: Patients with end-stage kidney disease have a high burden of PAD with poor long-term outcomes, which worsen, in an incremental fashion, with the involvement of each additional diseased arterial bed.

Impact of preexisting coronary artery and peripheral artery disease on outcomes in diabetic patients after kidney transplant.

BACKGROUND: Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. METHODS: This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. RESULTS: The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. CONCLUSIONS: Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival.

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.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. Objective: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. Design, Setting, and Participants: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. Intervention: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. Main Outcomes and Measures: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Results: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). Conclusions and Relevance: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors.

Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Orthostatic variation of pulmonary artery pressure in ambulatory heart failure patients.

AIM: To study effect of change in position (supine and standing) on pulmonary artery pressure (PAP) in ambulatory heart failure (HF) patients. METHODS: Seventeen patients with CardioMEMS® sensor and stable heart failure were consented and included in this single center study. Supine and standing measurements were obtained with at least 5 min interval between the two positions. These measurements included PAP readings utilizing the manufacturer handheld interrogator obtaining 10 s data in addition to the systemic blood pressure and heart rate recordings. RESULTS: Mean supine and standing readings and their difference (Δ) were as follows respectively: Systolic PAP were 33.4 (± 11.19), 23.6 (± 10) and Δ was 9.9 mmHg (p = 0.0001), diastolic PAP were 14.2 (± 5.6), 7.9 (± 5.7) and Δ was 6.3 mmHg (p = 0.0001) and mean PAP were 21.8 (± 7.8), 14 (± 7.2) and Δ was 7.4 mmHg (p = 0.0001) while the systemic blood pressure did not vary significantly. CONCLUSION: There is orthostatic variation of PAP in ambulatory HF patients demonstrating a mean decline with standing in diastolic PAP by 6.3 mmHg, systolic PAP by 9.9 mmHg and mean PAP by 7.4 mmHg in absence of significant orthostatic variation in systemic blood pressure or heart rate. These findings have significant clinical implications and inform that PAP in each patient should always be measured in the same position. Since initial readings at the time of implant were taken in supine position, it may be best to use supine position or to obtain a baseline standing PAP reading if standing PAP is planned on being used.

Prognostic Value of Hospital Frailty Risk Score and Clinical Outcomes in Patients Undergoing Revascularization for Critical Limb-Threatening Ischemia.

Background The impact of medical record-based frailty assessment on clinical outcomes in patients undergoing revascularization for critical limb-threatening ischemia (CLTI) is unknown. Methods and Results This study included patients with CLTI aged ≥18 years from the nationwide readmissions database 2016 to 2018 who underwent endovascular revascularization (ER) or surgical revascularization (SR). The hospital frailty risk score, a previously validated International Classification of Diseases, Tenth Edition, Clinical Modification (ICD-10-CM) claims-based score, was used to categorize patients into low- (<5), intermediate- (5-15), and high-risk (>15) frailty categories. Primary outcomes were in-hospital mortality and major amputation at 6 months. A total of 64 338 patients were identified who underwent ER (82.3%) or SR (17.7%) for CLTI. The mean (SD) age of the cohort was 69.3 (11.8) years, and 63% of patients were male. This study found a nonlinear association between hospital frailty risk score and in-hospital mortality and 6-month major amputation. In both ER and SR cohorts, the intermediate- and high-risk groups were associated with a significantly higher risk of in-hospital mortality (high-risk group: ER: odds ratio [OR], 7.2 [95% CI, 4.4-11.6], P<0.001; SR: OR, 28.6 [95% CI, 3.4-237.6], P=0.002) and major amputation at 6 months (high-risk group: ER: hazard ratio [HR], 1.6 [95% CI, 1.5-1.7], P<0.001; SR: HR, 1.7 [95% CI, 1.4-2.2], P<0.001) compared with the low-risk group. Conclusions The hospital frailty risk score, generated from the medical record, can identify frailty and predict in-hospital mortality and 6-month major amputation in patients undergoing ER or SR for CLTI. Further studies are needed to assess if this score can be incorporated into clinical decision-making in patients undergoing revascularization for CLTI.

Trends and Outcomes of Cardiogenic Shock in Patients With End-Stage Renal Disease: Insights From USRDS Database.

BACKGROUND: There is a paucity of data regarding epidemiology, temporal trends, and outcomes of patients with cardiogenic shock (CS) and end-stage renal disease (chronic kidney disease stage V on hemodialysis). METHODS: This is a retrospective cohort study using the United States Renal Data System database from January 1, 2006 to December 31, 2019. We analyzed trends of CS, percutaneous mechanical support (intraaortic balloon pump, percutaneous ventricular assist device [Impella and Tandemheart], and extracorporeal membrane oxygenation) utilization, index mortality, 30-day mortality, and 1-year all-cause mortality in end-stage renal disease patients. RESULTS: A total of 43 825 end-stage renal disease patients were hospitalized with CS (median age, 67.8 years [IQR, 59.4-75.8] and 59.1% men). From 2006 to 2019, the incidence of CS increased from 275 to 578 per 100 000 patients (Ptrend<0.001). The index mortality rate declined from 54.1% in 2006 to 40.8% in 2019 (Ptrend=0.44), and the 1-year all-cause mortality decreased from 63% in 2006 to 61.8% in 2018 (Ptrend=0.73), but neither trend was statistically significant. There was a significantly decreased utilization of intra-aortic balloon pumps from 17 832 to 7992 (Ptrend<0.001), increased utilization of percutaneous ventricular assist device from 137 to 5201 (Ptrend<0.001) and increase in extracorporeal membrane oxygenation use from 69 to 904 per 100 000 patients (Ptrend<0.001). After adjusting for covariates, there was no significant difference in index mortality between CS patients requiring percutaneous mechanical support versus those not requiring percutaneous mechanical support (odds ratio, 0.97 [CI, 0.91-1.02]; P=0.22). On multivariable regression analysis, older age, peripheral vascular disease, diabetes, and time on dialysis were independent predictors of higher index mortality. CONCLUSIONS: The incidence of CS in end-stage renal disease patients has doubled without significant change in the trend of index mortality despite the use of percutaneous mechanical support.

Causes and Predictors of 30-Day Readmission in Patients With COVID-19 and ST-Segment-Elevation Myocardial Infarction in the United States: A Nationwide Readmission Database Analysis.

Background Rates, causes, and predictors of readmission in patients with ST-segment-elevation myocardial infarction (STEMI) during COVID-19 pandemic are unknown. Methods and Results All hospitalizations for STEMI were selected from the US Nationwide Readmissions Database 2020 and were stratified by the presence of COVID-19. Primary outcome was 30-day readmission. Multivariable hierarchical generalized logistic regression analysis was performed to compare 30-day readmission between patients with STEMI with and without COVID-19 and to identify the predictors of 30-day readmissions in patients with STEMI and COVID-19. The rate of 30-day all-cause readmission was 11.4% in patients with STEMI who had COVID-19 and 10.6% in those without COVID-19, with the adjusted odds ratio (OR) not being significantly different between the two groups (OR, 0.88 [95% CI, 0.73-1.07], P=0.200). Of all 30-day readmissions in patients with STEMI and COVID-19, 41% were for cardiac causes. Among the cardiac causes, 56% were secondary to acute coronary syndrome, while among the noncardiac causes, infections were the most prevalent. Among the causes of 30-day readmissions, infectious causes were significantly higher for patients with STEMI who had COVID-19 compared with those without COVID-19 (29.9% versus 11.3%, P=0.001). In a multivariable model, congestive heart failure, chronic kidney disease, low median household income, and length of stay ≥5 days were found to be associated with an increased risk of 30-day readmission. Conclusions Post-STEMI, 30-day readmission rates were similar between patients with and without COVID-19. Cardiac causes were the most common causes for 30-day readmissions, and infections were the most prevalent noncardiac causes.

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.

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.

Undernutrition Severity Is Associated With Worse Outcomes in Patients With Acute Myocardial Infarction.

Malnutrition has been associated with inferior outcomes in patients admitted with acute myocardial infarction (AMI). However, there is a lack of data to assess if the degree of malnutrition correlates with outcome severity. We used the Nationwide Readmission Database for 2016 to 2019 in our cross-sectional study. First, we extracted all cases older than 18 years that include a primary diagnosis of AMI. Appropriate survey and domain analyses were applied to obtain the national estimates using Statistical Analysis Software 9.4. We identified 2,280,393 discharges for AMI. Malnutrition was present in 4% of the study cohort (or 89,490 cases). Half of the patients with malnutrition (or 44,919) had moderate-to-severe malnutrition. The other 44,371 (or 50%) had a milder degree of malnutrition. Patients with malnutrition were younger than those without malnutrition (mean age 72 vs 75 years, p <0.001) and were more often women (48% vs 37%, p <0.001). Patients with malnutrition had a higher prevalence of underlying heart failure, dementia, coagulopathy, and chronic (liver, renal, and lung) diseases (p <0.001). Patients with malnutrition also had a significantly higher inpatient mortality (12.5% vs 4.6%, p <0.001), length of stay (mean of 13 vs 7 days, p <0.001), and 30-day all-cause readmission rates (19% vs 13%, p <0.001). Inpatient mortality on readmission was also higher in those with malnutrition (2% vs 0.6%, p <0.001). The univariate analysis showed that the severity of malnutrition also correlated with a higher inpatient mortality (odds ratio [OR] 2.34 [2.24 to 2.46] for mild malnutrition and 3.65 [3.49 to 3.82] for advanced malnutrition). After adjusting for age, gender, heart failure, dementia, coagulopathy, chronic (liver, renal, and lung) diseases, and history of cardiovascular revascularization, the presence of malnutrition and the severity of malnutrition continued to be associated with a higher inpatient mortality than those without malnutrition (OR 1.20 [1.14 to 1.26] for mild malnutrition and OR 1.69 [1.61 to 1.78] for more severe malnutrition). In conclusion, underlying malnutrition is associated with worse outcomes in patients hospitalized with AMI. The severity of malnutrition also correlates with worse outcomes.