Faculty Bibliography

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi-site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered <80% over 6 months. We assessed the association between copayment and nonadherence using multivariable logistic regression, and nonbinarized proportion of days covered using multivariable Poisson regression, adjusting for demographic, clinical, and neighborhood-level covariates. A total of 921 patients met inclusion criteria, with 192 (20.8%) having $0 copayment, 228 (24.8%) with $0.01 to $10 copayment, 206 (22.4%) with $10.01 to $100, and 295 (32.0%) with >$100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P<0.001). After multivariable adjustment, odds of nonadherence were significantly higher for copayment of $10.01 to $100 (odds ratio [OR], 1.93 [95% CI, 1.15-3.27], P=0.01) or >$100 (OR, 2.58 [95% CI, 1.63-4.18], P<0.001), as compared with $0 copayment. Similar associations were seen when assessing proportion of days covered as a proportion. Conclusions We found higher rates of not filling ARNI prescriptions among patients with higher copayments, which persisted after multivariable adjustment. Our findings support future studies to assess whether reducing copayments can increase adherence to ARNI and improve outcomes for heart failure.

Randomized clinical trials have not demonstrated a survival benefit with percutaneous coronary intervention in stable ischemic heart disease (SIHD). We evaluated the generalizability of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial findings to the broader population of veterans with SIHD. Veterans who underwent coronary angiography between 2005 and 2013 for SIHD were identified from the Veterans Affairs Clinical Assessment, Reporting and Tracking Program (VA CART). Patient-level comparisons were made between patients from VA CART who met the eligibility criteria for COURAGE and veterans enrolled in COURAGE between 1999 and 2004. All-cause mortality over long-term follow-up was assessed using Cox proportional hazards models. COURAGE-eligible patients from VA CART (n = 59,758) were older, had a higher body mass index, a greater prevalence of co-morbidities, but fewer diseased vessels on index coronary angiography, and were less likely to be on optimal medical therapy at baseline and on 1-year follow-up compared with VA COURAGE participants (n = 968). Patients from VA CART (median follow-up 6.5 years) had higher all-cause mortality (adjusted hazard ratio [aHR] 1.98 [1.61 to 2.43]) than participants from VA COURAGE (median follow-up: 4.6 years). Risks of mortality were greater in the 56.4% patients from CART who were medically managed (aHR 1.94 [1.49 to 2.53]) and in the 43.6% who underwent percutaneous coronary intervention (aHR 1.99 [1.45 to 2.74]), compared with their respective VA COURAGE arms. In conclusion, in this noncontemporaneous patient-level analysis, veterans in the randomized COURAGE trial had more favorable outcomes than the population of veterans with SIHD at large.

Aims/UNASSIGNED:We aimed to use optical coherence tomography (OCT) to identify differences in atherosclerotic culprit lesion morphology in women with myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) compared with MI with obstructive coronary artery disease (MI-CAD). Methods and results/UNASSIGNED:Women with an OCT-determined atherosclerotic aetiology of non-ST segment elevation (NSTE)-MINOCA (angiographic diameter stenosis <50%) who were enrolled in the multicentre Women's Heart Attack Research Program (HARP) study were compared with a consecutive series of women with NSTE-MI-CAD who underwent OCT prior to coronary intervention at a single institution. Atherosclerotic pathologies identified by OCT included plaque rupture, plaque erosion, intraplaque haemorrhage (IPH, a region of low signal intensity with minimum attenuation adjacent to a lipidic plaque without fibrous cap disruption), layered plaque (superficial layer with clear demarcation from the underlying plaque indicating early thrombus healing), or eruptive calcified nodule.We analysed 58 women with NSTE-MINOCA and 52 women with NSTE-MI-CAD. Optical coherence tomography features of underlying vulnerable plaque (thin-cap fibroatheroma) were less common in MINOCA (3 vs. 35%) than in MI-CAD. Intraplaque haemorrhage (47 vs. 2%) and layered plaque (31 vs. 12%) were more common in MINOCA than MI-CAD, whereas plaque rupture (14 vs. 67%), plaque erosion (8 vs. 14%), and calcified nodule (0 vs. 6%) were less common in MINOCA. The angle of ruptured cavity was smaller and thrombus burden was lower in MINOCA. Conclusion/UNASSIGNED:The prevalence of atherothrombotic culprit lesion subtype varied substantially between MINOCA and MI-CAD. A majority of culprit lesions in MINOCA had the appearance of IPH or layered plaque. Clinical Trial Registration Information/UNASSIGNED:

BACKGROUND:Type 2 myocardial infarction (MI) occurs due to a mismatch in myocardial oxygen supply and demand without unstable coronary artery disease. We sought to identify patterns, predictors and outcomes of invasive management of type 2 MI in the USA. METHODS:Adults aged ≥18 years hospitalized with type 2 MI were identified in a cross-sectional study from the 2018 National Inpatient Sample. Invasive management was defined as invasive coronary angiography or revascularization. Patient, hospital and geographic characteristics associated with invasive management were identified by multivariable logistic regression. Propensity-matched cohorts were generated to evaluate associations between invasive vs. conservative management and mortality. RESULTS:We identified 268 850 admissions with type 2 MI in 2018. Type 2 MI patients had a high burden of comorbidities and were commonly admitted with diagnoses of circulatory (39.7%), infectious (23.1%) or respiratory (10.8%) illness. Only 11.2% of type 2 MI were managed invasively, of which 17.9% underwent coronary revascularization. Odds of invasive management were higher with commercial insurance [adjusted OR (aOR) 1.39; 95% confidence interval (CI), 1.27-1.52] and lower with Medicaid (aOR 0.86; 95% CI, 0.76-0.96) vs. Medicare. Significant heterogeneity in invasive management of type 2 MI was observed by geographic region (range 7.2-13.8%), independent of patient and hospital factors. Invasive management was associated with lower in-hospital mortality than conservative management overall (3.9 vs. 9.1%; P < 0.001) and in propensity-matched analyses (OR, 0.70; 95% CI, 0.59-0.84). CONCLUSION/CONCLUSIONS:Invasive management of type 2 MI varies by insurance status and geography, highlighting uncertainty regarding optimal management and potential disparities in clinical care.

Randomized controlled trials (RCTs) remain the gold standard to evaluate clinical interventions, producing the highest level of evidence while minimizing potential bias. Inadequate recruitment is a commonly encountered problem that undermines the completion and generalizability of RCTs-and is even more challenging when enrolling amidst a pandemic. Here, we reflect on our experiences with virtual recruitment of non-hospitalized patients in the United States for ColCorona, an international, multicenter, randomized, placebo-controlled coronavirus disease 2019 (COVID-19) drug trial. Recruitment challenges during a pandemic include constraints created by shelter-in-place policies and targeting enrollment according to national and local fluctuations in infection rate. Presenting a study to potential participants who are sick with COVID-19 and may be frightened, overwhelmed, or mistrusting of clinical research remains a challenge. Strategies previously reported to improve recruitment include transparency, patient and site education, financial incentives, and person-to-person outreach. Active measures taken during ColCorona to optimize United States recruitment involved rapid expansion of sites, adjustment of recruitment scripts, assessing telephone calls versus text messages for initial contact with participants, institutional review board-approved financial compensation, creating an infrastructure to systematically identify potentially eligible patients, partnering with testing sites, appealing to both self-interest and altruism, and large-scale media efforts with varying degrees of success.