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Antiplatelet therapy is the cornerstone of the secondary prevention of cardiovascular disease. Aspirin is indicated for all patients with chronic coronary disease to prevent recurrent ischemic events. A more potent antithrombotic therapy—including P2Y12 inhibitor monotherapy, dual antiplatelet therapy, or vascular dose anticoagulation—reduces the risk of ischemic events but also increases bleeding risk. Clinicians must weigh both ischemic risks and bleeding risks when determining an optimal antithrombotic therapy for patients with chronic coronary disease, and soliciting patient involvement in shared decision-making is critical.

IMPORTANCE: Inadequate representation of older patients, women, and racial minority individuals in cardiovascular clinical trials limits both the generalizability of trial findings and inclusivity in access to novel therapies and therapeutic strategies. OBJECTIVE: To report on temporal trends in the representation of older patients, women, and racial and ethnic minority individuals in clinical trials studying treatments for valvular heart disease. EVIDENCE REVIEW: All published clinical trials enrolling more than 100 adults with any valvular heart disease published between 2005 and 2020 were included after searches with PubMed and ClinicalTrials.gov. Data on age, sex, race, and ethnicity reported in the included studies were collected. Trials were assigned to 4 time periods based on the publication date, and temporal trends were analyzed in the representation of older patients, women, and racial and ethnic minority individuals. FINDINGS: A total of 139 clinical trials with 51 527 participants were identified. Of these trials, 103 (74%) investigated aortic valve disease and the remainder mitral valve disease. Overall, 63 trials (45.3%) enrolled patients only in Europe, 24 (17.3%) only in North America, and 19 (13.7%) in multiple geographical regions. The weighted mean (SD) age of enrolled patients was 68.4 (11.4) years, increasing nonsignificantly from 61.9 (5.9) years in 2005-2008 to 72.8 (9.6) years in 2017-2020 (P = .09 for trend). The overall proportion of women enrolled in valvular heart disease trials was 41.1%, with no significant changes over time. Data on race and ethnicity of trial participants were reported in 13 trials (9.4%), in which trial-level representation of American Indian/Alaska Native, Asian, Black/African American, Hispanic, and Native Hawaiian/Pacific Islander patients ranged from 0.27% to 43.9%. There were no significant temporal trends noted in the enrollment of racial and ethnic minority populations. The representation of women in clinical trials was positively associated with enrollment rates of older patients and underrepresented racial and ethnic groups. CONCLUSIONS AND RELEVANCE: This review found that over the past 2 decades, women and racial and ethnic minority individuals have remained underrepresented in North American valvular heart disease clinical trials. Further work is needed to improve the reporting of race and ethnicity data and address barriers to trial enrollment for older patients, women, and racial and ethnic minority individuals.

IMPORTANCE: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials. OBJECTIVE: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022. EXPOSURES: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals. MAIN OUTCOME AND MEASURES: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies. RESULTS: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code–based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, −2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials. CONCLUSIONS AND RELEVANCE: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban have transformed the management of atrial fibrillation (AF), but are only approved by regulatory authorities for stroke prophylaxis in patients with so-called “non-valvular AF.” This terminology has spawned confusion about which patients with valvular heart disease benefit from NOACs and which should be treated with vitamin K antagonists (VKAs) instead. Patients with valvular heart disease other than mechanical prosthetic valves or severe mitral stenosis (including those with bioprosthetic valves) were included in pivotal trials demonstrating the benefit of NOACs over VKAs, and consensus guidelines recommend NOACs over VKAs in these patients. Subsequent devoted randomized controlled trials in patients with AF and bioprosthetic valves, including transcatheter valves, have confirmed the safety of NOACs in this population. In patients with rheumatic mitral stenosis, observational studies indicate that NOACs may be safe and effective, but randomized controlled trials are ongoing. By contrast, a randomized controlled trial showed that dabigatran is harmful in patients with mechanical prosthetic mitral valves; however, these data may not extrapolate to patients with mechanical valve prostheses in other locations or to other NOACs, and randomized controlled trials are ongoing. In this review, we discuss these data in greater depth, and make recommendations for the use of NOACs in patients with valvular heart disease.

IMPORTANCE: Despite the benefits of high-technology therapeutics, inequitable access to these technologies may generate disparities in care. OBJECTIVE: To examine the association between zip code–level racial, ethnic, and socioeconomic composition and rates of transcatheter aortic valve replacement (TAVR) among Medicare patients living within large metropolitan areas with TAVR programs. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, nationwide cross-sectional analysis of Medicare claims data between January 1, 2012, and December 31, 2018, included beneficiaries of fee-for-service Medicare who were 66 years or older living in the 25 largest metropolitan core-based statistical areas. EXPOSURE: Receipt of TAVR. MAIN OUTCOMES AND MEASURES: The association between zip code–level racial, ethnic, and socioeconomic composition and rates of TAVR per 100 000 Medicare beneficiaries. RESULTS: Within the studied metropolitan areas, there were 7590 individual zip codes. The mean (SD) age of Medicare beneficiaries within these areas was 71.4 (2.0) years, a mean (SD) of 47.6% (5.8%) of beneficiaries were men, and a mean (SD) of 4.0% (7.0%) were Asian, 11.1% (18.9%) were Black, 8.0% (12.9%) were Hispanic, and 73.8% (24.9%) were White. The mean number of TAVRs per 100 000 Medicare beneficiaries by zip code was 249 (IQR, 0-429). For each $1000 decrease in median household income, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.2% (95% CI, 0.1%-0.4%) lower (P = .002). For each 1% increase in the proportion of patients who were dually eligible for Medicaid services, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 2.1% (95% CI, 1.3%-2.9%) lower (P < .001). For each 1-unit increase in the Distressed Communities Index score, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.4% (95% CI, 0.2%-0.5%) lower (P < .001). Rates of TAVR were lower in zip codes with higher proportions of patients of Black race and Hispanic ethnicity, despite adjusting for socioeconomic markers, age, and clinical comorbidities. CONCLUSIONS AND RELEVANCE: Within major metropolitan areas in the US with TAVR programs, zip codes with higher proportions of Black and Hispanic patients and those with greater socioeconomic disadvantages had lower rates of TAVR, adjusting for age and clinical comorbidities. Whether this reflects a different burden of symptomatic aortic stenosis by race and socioeconomic status or disparities in use of TAVR requires further study.

IMPORTANCE: Pharmacy fill data are increasingly accessible to clinicians and researchers to evaluate longitudinal medication persistence beyond patient self-report. OBJECTIVE: To assess the agreement and accuracy of patient-reported and pharmacy fill–based medication persistence. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the cluster randomized clinical trial ARTEMIS (Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) enrolled patients at 287 US hospitals (131 randomized to intervention and 156 to usual care) from June 5, 2015, to September 30, 2016, with 1-year follow-up and blinded adjudication of major adverse cardiovascular events. In total, 8373 patients with myocardial infarction and measurement of P2Y12 inhibitor persistence by both patient self-report and pharmacy data were included. Serum P2Y12 inhibitor drug levels were measured for 944 randomly selected patients. Data were analyzed from May 2018 to November 2019. INTERVENTIONS: Patients treated at intervention-arm hospitals received study vouchers to offset copayments at each P2Y12 inhibitor fill for 1 year after myocardial infarction. MAIN OUTCOMES AND MEASURES: Nonpersistence was defined as a gap of 30 days or more in P2Y12 inhibitor use (patient report) or supply (pharmacy fill) and as serum P2Y12 inhibitor levels below the lower limit of quantification (drug level). Among patients in the intervention arm, a “criterion standard” definition of nonpersistence was a gap of 30 days or more in P2Y12 inhibitor use by both voucher use and pharmacy fill. Major adverse cardiovascular events were defined as adjudicated death, recurrent myocardial infarction, or stroke. RESULTS: Of 8373 patients included in this analysis, the median age was 62 years (interquartile range, 54-70 years), 5664 were men (67.7%), and 990 (11.8%) self-reported as nonwhite race/ethnicity. One-year estimates of medication nonpersistence rates were higher using pharmacy fills (4042 patients [48.3%]) compared with patient self-report (1277 patients [15.3%]). Overall, 4185 patients (50.0%) were persistent by both pharmacy fill data and patient report, 1131 patients (13.5%) were nonpersistent by both, and 3057 patients (36.5%) were discordant. By application of the criterion standard definition, the 1-year nonpersistence rate was 1184 of 3703 patients (32.0%); 892 of 3318 patients (26.9%) in the intervention arm who self-reported persistence were found to be nonpersistent, and 303 of 1487 patients (20.4%) classified as nonpersistent by pharmacy fill data were actually persistent. Agreement between serum P2Y12 inhibitor drug levels and either patient-reported (κ = 0.11-0.23) or fill-based (κ = 0.00-0.19) persistence was poor. Patients who were nonpersistent by both pharmacy fill data and self-report had the highest 1-year major adverse cardiac event rate (18.3%; 95% CI, 16.0%-20.6%) compared with that for discordant patients (9.7%; 8.7%-10.8%) or concordantly persistent patients (8.2%; 95% CI, 7.4%-9.0%). CONCLUSIONS AND RELEVANCE: Patient report overestimated medication persistence rates, and pharmacy fill data underestimated medication persistence rates. Patients who are nonpersistent by both methods have the worst clinical outcomes and should be prioritized for interventions that improve medication-taking behavior. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02406677

Peripheral vascular intervention (PVI) improves quality of life and reduces major adverse limb events in patients with peripheral arterial disease. PVI is commonly performed via the femoral artery, and the most common adverse periprocedural event is a vascular access complication. Transradial access for PVI has the potential to reduce vascular access complications and improve patient outcomes. Further study is needed to elucidate the risks of stroke, acute kidney injury, and radiation exposure in the setting of transradial PVI. As transradial access for PVI progresses, it will be important to build the evidence base along with procedural experience.

IMPORTANCE: The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) cluster-randomized trial found that copayment reduction for P2Y12 inhibitors improved 1-year patient persistence in taking that medication. OBJECTIVE: To assess whether providing copayment reduction for P2Y12 inhibitors increases patient persistence in taking other secondary prevention cardiovascular medications. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the ARTEMIS trial includes data from 287 hospitals that enrolled patients between June 2015 and September 2016. Patients hospitalized with acute myocardial infarction were included. Data analysis occurred from May 2018 through August 2019. INTERVENTIONS: Hospitals randomized to the intervention provided patients vouchers that waived copayments for P2Y12 inhibitors fills for 1 year. Hospitals randomized to usual care did not provide study vouchers. MAIN OUTCOMES AND MEASURES: Persistence in taking β-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medications at 1 year, defined as the absence of a gap in medication supply of 30 or more days by pharmacy fill data in the intervention-arm (intent-to-treat) population. RESULTS: A total of 131 hospitals (with 5109 patients) were randomized to the intervention, and 156 hospitals (with 3264 patients) randomized to the control group. Patients discharged from intervention hospitals had higher persistence in taking statins (2247 [46.1%] vs 1300 [41.9%]; adjusted odds ratio, 1.11 [95% CI, 1.00-1.24]), and β-blockers (2235 [47.6%] vs 1277 [42.5%]; odds ratio, 1.23 [95% CI, 1.10-1.38]), although the association was smaller than that seen for P2Y12 inhibitors (odds ratio, 1.47 [95% CI, 1.29-1.66]). Persistence in taking angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers were also numerically higher among patients in the intervention arm than in the usual-care arm, but this was not significant after risk adjustment (1520 [43.9%] vs 847 [40.5%]; adjusted odds ratio, 1.10 [95% CI, 0.97-1.24]). Patients in the intervention arm reported greater financial burden associated with medication cost than the patients in the usual-care arm at baseline, but these differences were no longer significant at 1 year. CONCLUSIONS AND RELEVANCE: Reducing patient copayments for 1 medication class increased persistence not only to that therapy class but may also have modestly increased persistence to other post–myocardial infarction secondary prevention medications. These findings have important implications for the clinical utility and cost-effectiveness of medication cost-assistance programs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02406677

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IMPORTANCE: Intensive care unit (ICU) utilization may have important implications for the care and outcomes of patients with non–ST-segment elevation myocardial infarction (NSTEMI). OBJECTIVES: To examine interhospital variation in ICU utilization in the United States for older adults with hemodynamically stable NSTEMI and outcomes associated with ICU utilization among patients with low, moderate, or high mortality risk. DESIGN, SETTING, AND PARTICIPANTS: This study was a retrospective analysis of 28 018 Medicare patients 65 years or older admitted with NSTEMI to 346 hospitals participating in the Acute Coronary Treatment and Intervention Outcomes Network (ACTION)–Get With the Guidelines from April 1, 2011, through December 31, 2012. Patients with cardiogenic shock or cardiac arrest on presentation were excluded. Data analysis was performed from May 7 through October 8, 2015. EXPOSURES: Hospitals with high (>70% of patients with NSTEMI treated in an ICU during the index hospitalization), intermediate (30%-70%), or low (<30%) ICU utilization. MAIN OUTCOMES AND MEASURES: Thirty-day mortality. RESULTS: Of 28 018 patients with NSTEMI 65 years or older (median age, 77 years [interquartile range, 71-84 years]; female, 13 055 [46.6%]; nonwhite race, 3931 [14.0%]), 11 934 (42.6%) had an ICU stay. The proportion of patients with NSTEMI treated in the ICU varied across hospitals (median, 38%; interquartile range, 26%-54%), but no significant differences were found in hospital or patient characteristics among high, intermediate, or low ICU utilization hospitals. Compared with high ICU utilization hospitals, low or intermediate ICU utilization hospitals were only marginally more selective of higher-risk patients, as determined by ACTION in-hospital mortality risk score or initial troponin level. The median ACTION risk score for patients treated in the ICU at low and intermediate ICU utilization hospitals was 34 compared with 33 for patients not treated in the ICU; at high ICU utilization hospitals, the median ACTION mortality risk score was 33 for patients treated in the ICU and 34 for patients not treated in the ICU. Thirty-day mortality rates did not significantly differ based on hospital ICU utilization (high vs low: 8.7% vs 8.7%; adjusted odds ratio, 0.91; 95% CI, 0.76-1.08; intermediate vs low: 9.6% vs 8.7%; adjusted odds ratio, 1.06; 95% CI, 0.94-1.20). The association between hospital ICU utilization and mortality did not change when considered among patients with ACTION risk scores greater than 40, 30 to 40, and less than 30 (adjusted interaction P = .86). CONCLUSIONS AND RELEVANCE: Utilization of the ICU for older patients with NSTEMI varied significantly among hospitals. This variability was not explained by hospital characteristics or driven by patient risk. Mortality after myocardial infarction did not significantly differ among high, intermediate, or low ICU utilization hospitals.

Platelets play a key role in mediating stent thrombosis, which is the major cause of ischemic events immediately after percutaneous coronary intervention (PCI). Antiplatelet therapy is therefore the cornerstone of antithrombotic therapy after PCI. However, the use of antiplatelet agents increases bleeding risk, with more potent antiplatelet agents further increasing bleeding risk. In the past 5 years, potent and fast-acting P2Y12 inhibitors have augmented the antiplatelet armamentarium available to interventional cardiologists. This article reviews the preclinical and clinical data surrounding these new agents, and discusses the significant questions and controversies that still exist regarding the optimal antiplatelet strategy.

Despite advances in medical therapy for chronic heart failure (HF), advanced HF carries a dismal prognosis. Options such as transplantation and durable mechanical circulatory support have greatly improved outcomes for these patients, but their introduction has introduced significant complexity to patient management. Although much of this management occurs at specialized heart transplant centers, it is the responsibility of the primary cardiologist of the patient with advanced HF to refer patients at the appropriate time and to help them navigate the difficult decisions related to the pursuit of advanced therapies. We present a unique pathway that incorporates guidelines, recent data, and expert opinion to help general cardiologists determine which patients should be referred for transplantation or durable mechanical circulatory support, and when they should be referred. Decision making on referral to the heart transplant center is also summarized.

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IMPORTANCE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduce deaths from cardiovascular conditions, hospitalizations for heart failure, and progression of kidney disease among patients with type 2 diabetes. Black individuals have a disproportionate burden of cardiovascular and chronic kidney disease (CKD). Adoption of novel therapeutics has been slower among Black and female patients and among patients with low socioeconomic status than among White or male patients or patients with higher socioeconomic status. OBJECTIVE: To assess whether inequities based on race/ethnicity, gender, and socioeconomic status exist in SGLT2 inhibitor use among patients with type 2 diabetes in the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of commercially insured patients in the US was performed from October 1, 2015, to June 30, 2019, using the Optum Clinformatics Data Mart. Adult patients with a diagnosis of type 2 diabetes, including those with heart failure with reduced ejection fraction (HFrEF), atherosclerotic cardiovascular disease (ASCVD), or CKD, were evaluated in the analysis. MAIN OUTCOMES AND MEASURES: Prescription of an SGLT2 inhibitor. Multivariable logistic regression models were used to assess the association of race/ethnicity, gender, and socioeconomic status with SGLT2 inhibitor use. RESULTS: Of 934?737 patients with type 2 diabetes (mean [SD] age, 65.4 [12.9] years; 50.7% female; 57.6% White), 81?007 (8.7%) were treated with an SGLT2 inhibitor during the study period. Between 2015 and 2019, the percentage of patients with type 2 diabetes treated with an SGLT2 inhibitor increased from 3.8% to 11.9%. Among patients with type 2 diabetes and cardiovascular or kidney disease, the rate of SGLT2 inhibitor use increased but was lower than that among all patients with type 2 diabetes (HFrEF: 1.9% to 7.6%; ASCVD: 3.0% to 9.8%; CKD: 2.1% to 7.5%). In multivariable analyses, Black race (adjusted odds ratio [aOR], 0.83; 95% CI, 0.81-0.85), Asian race (aOR, 0.94; 95% CI, 0.90-0.98), and female gender (aOR, 0.84; 95% CI, 0.82-0.85) were associated with lower rates of SGLT2 inhibitor use, whereas higher median household income (=$100?000: aOR, 1.08 [95% CI, 1.05-1.10]; $50 000-$99 999: aOR, 1.05 [95% CI, 1.03-1.07] vs <$50 000) was associated with a higher rate of SGLT2 inhibitor use. These results were similar among patients with HFrEF, ASCVD, and CKD. CONCLUSIONS AND RELEVANCE: In this cohort study, use of an SGLT2 inhibitor treatment increased among patients with type 2 diabetes from 2015 to 2019 but remained low, particularly among patients with HFrEF, CKD, and ASCVD. Black and female patients and patients with low socioeconomic status were less likely to receive an SGLT2 inhibitor, suggesting that interventions to ensure more equitable use are essential to prevent worsening of well-documented disparities in cardiovascular and kidney outcomes in the US.

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Background:Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are utilized when available, and their impact on medication persistence is unknown.Methods:The ARTEMIS trial randomized 135 hospitals to provide patients with vouchers that offset copayment costs when filling P2Y12inhibitors in the 1 year post-myocardial infarction (MI). We used multivariable logistic regression to identify patient characteristics associated with voucher use among intervention patients. We compared 90-day and 1-year P2Y12inhibitor persistence (no gap in pharmacy supply >30 days) between randomized intervention and usual care patients in tertiles stratified by likelihood of voucher use.Results:Among 6,135 patients treated at hospitals randomized to provide the copayment intervention, 1,742 (28.4%) never used the voucher, though 1,729 (99.2% of these) filled at least one P2Y12inhibitor prescription in the 1 year post-MI. Patients discharged on ticagrelor, those discharged with a planned 1-year course of P2Y12inhibitor treatment, and patients who were white, commercially insured, or had higher out of pocket medication costs were more likely to use vouchers (c-index 0.74). Applying this model to stratify all enrolled patients (n=10,102) by likelihood of voucher use, we observed the intervention to improve medication persistence the most in patients with high likelihood of voucher use (interaction p = 0.03 at 1 year, Figure).Conclusions:Patients at high likelihood of voucher use benefit the most from copayment assistance. This study identified patients unlikely to comply with voucher use for whom other measures are needed to improve medication use.

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