Background: Compared to traditional risk factors, coronary artery calcium (CAC) scores improve prognostic accuracy for atherosclerotic cardiovascular disease (ASCVD) outcomes. However, the relative impact of statins on ASCVD outcomes stratified by CAC scores is unknown. Objectives: To determine if CAC can identify patients most likely to benefit from statin treatment. Methods: We identified consecutive subjects without pre-existing ASCVD or malignancy who underwent CAC scoring from 2002 to 2009 at Walter Reed. The primary outcome was first major adverse cardiovascular event (MACE), a composite of acute myocardial infarction, stroke, and cardiovascular death. The effect of statin therapy on outcomes was analyzed stratified by CAC presence and severity, after adjusting for baseline comorbidities with inverse probability of treatment weights based on propensity scores. Results: 13,644 patients (mean age 50 years; 71% men) were followed for a median of 9.4 years. Comparing patients with and without statin exposure, statin therapy was associated with reduced risk of MACE in patients with CAC (adjusted subhazard ratio [aSHR] 0.76, 95% CI 0.60–0.95, p=0.015) but not in patients without CAC (aSHR 1.00, 95% CI 0.79–1.27, p=0.99). The effect of statin use on MACE was significantly related to the severity of CAC (p <0.0001 for interaction), with the NNT to prevent one initial MACE outcome over 10 years ranging from 100 (CAC 1–100) to 12 (CAC >100). Conclusions: In a large-scale cohort without baseline ASCVD, the presence and severity of CAC identified patients most likely to benefit from statins for the primary prevention of cardiovascular diseases. Condensed Abstract: Prior studies have shown that coronary artery calcium (CAC) screening improves risk prediction of atherosclerotic cardiovascular disease (ASCVD), but the true impact of statins on ASCVD outcomes stratified by CAC scores is unknown. In this retrospective cohort of 13,644 patients without pre-existing atherosclerotic cardiovascular disease or malignancy who underwent CAC scoring at Walter Reed Army Medical Center, increasing severity of CAC was associated with increased benefit from statin treatment for the prevention of cardiovascular morbidity and mortality. CAC presence and severity may help stratify patients most likely to benefit from statins.

Author Contributions: Drs Winn and Crotty had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

BACKGROUND: We extend an interrupted time series study design to identify heterogeneous treatment effects using group based trajectory models (GBTM) to identify groups before a new policy and then examine if the effects of the policy has consistent impacts across groups using propensity score weighting to balance individuals within trajectory groups who are and are not exposed to the policy change. We explore this by examining how adherence to endocrine therapy (ET) for women with breast cancer was impacted by reducing copayments for medications by the introduction of generic ETs among women who do not receive a subsidy (the “treatment” group) to those that do receive a subsidy and are not exposed to any changes in copayments (the “control” group). METHODS: We examined monthly adherence to ET using the proportion of days covered (PDC) for women diagnosed with breast cancer between 2008–2009 using SEER-Medicare data. To account for baseline trends, we characterize adherence for 1 year before generic approval of ET using GBTM, within each groups we generate inverse probability treatment weights of not receiving a subsidy. We compared adherence after generic entry within each GBTM using a modified Poisson model. RESULTS: GBTM for adherence in the one-year pre-generic identified six groups. When comparing patients that did and did not receive a subsidy we found no overall effect of generic introduction. However, 1 of the 6 identified adherence groups post-generic adherence increased (the “consistently low” (RR=1.91; 95% CI=1.34–2.72)). CONCLUSIONS: This study describes a new approach to identify heterogeneous effects when using an interrupted time series research design.

Aims The accuracy of an apical‐sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice. Methods and results As strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We determined the performance characteristics for echocardiographic strain findings in discriminating CA including apical sparing, the ejection fraction to global longitudinal strain ratio (EF/GLS), and the septal apical–septal basal ratio (SA/SB); other clinical predictors of confirmed CA; and predictors of patients who underwent complete evaluation for CA. CA was confirmed by endomyocardial biopsy or diagnostic cardiac imaging. A total of 547 TTEs, representing 451 patients, reported concern for CA and had adequate strain for analysis. A total of 111 patients underwent complete evaluation for amyloidosis with 100 patients undergoing complete cardiac evaluation for CA. In those 100 patients, multivariable predictors of confirmed CA were age [odds ratio (OR) 3.37 per 5 years], a visual apical‐sparing pattern (OR 10.85), and left ventricular ejection fraction (LVEF)/GLS > 4.1 (OR 35.37). CA was less likely in those with coronary artery disease (OR 0.04), hypertension (OR 0.18), and increased systolic blood pressure (OR 0.60 per 5 mm Hg increase). SA/SB [area under the curve (AUC) 0.72, 95% confidence interval (CI) 0.60–0.84] and LVEF/GLS (AUC 0.72, 95% CI 0.60–0.84) both had improved discrimination for CA compared with the apical‐sparing ratio (AUC 0.66, 95% CI 0.54–0.79). Many patients with suggestive TTE findings did not receive an evaluation for amyloidosis. Complete evaluation was more likely with Caucasian race (OR 2.1), increased septal thickness (OR 1.4), increased body mass index (OR 1.2), and if the report specifically stated ‘amyloid’ (OR 1.9). Evaluations were less likely in patients with comorbidities. While hypertension reduced the likelihood of evaluating for CA, 34% of patients with CA had hypertension (>130/80 mm Hg) at time of diagnosis. Conclusions In a broad population of patients undergoing TTE, apical sparing on strain imaging increased the likelihood of CA diagnosis but with modest sensitivity and specificity. GLS/EF ratio may be a more reliable tool to screen for CA. The low rate of complete evaluation in patients with concerning TTE findings indicates a strong need for practice improvement and enhanced disease awareness.

Background One‐third to one‐half of patients prescribed adjuvant endocrine therapy are nonadherent during the recommended 5‐year endocrine therapy course. This study investigated whether poor pharmacy synchronization of medication fills (requiring refills on different days) acts as a barrier to adherence. Methods A cohort of older women with stage 0 to III endocrine receptor–positive breast cancer in 2011 was identified from the Surveillance, Epidemiology, and End Result–Medicare claims‐linked cancer registry. Women with endocrine therapy and at least 1 other medication fill were identified, and the 3‐month synchronization of their fills was calculated as 1 minus the quotient of the number of pharmacy visits and the number of filled medications. Regression models were used to examine the association between synchronization (in quartiles adjusted for the number of medications) and adherence to endocrine therapy (defined as a medication possession ratio ≥80%) over the subsequent year. Results During the 3 months after the first endocrine therapy prescription, the study cohort of 3212 women had a mean of 8.6 pharmacy visits (standard deviation, 4.7) with a mean synchronization of 0.3 (standard deviation, 0.2). Those in the third (odds ratio, 1.29; 95% confidence interval, 1.04‐1.59) and fourth (most) medication number–adjusted synchronization quartiles (odds ratio, 1.49; 95% confidence interval, 1.19‐1.86) were more likely to be adherent than those in the least. Multivariate model predictions showed that the proportion of patients who were adherent over 1 year varied from 68.9% in the least synchronized quartile to 76.6% in the most synchronized one. Conclusions Prescription refill synchronization is strongly associated with adherence to endocrine therapy. Efforts to improve adherence should address this.

BACKGROUND: Patients with cancer-related pain are underrepresented in the opioid literature despite high opioid exposure and numerous risk factors for adverse opioid outcomes, including unnecessary persistent opioid use. The objective of this study was to determine the extent, historical trends, and predictors of new-onset persistent opioid use among older adult women after active breast cancer treatment. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data for opioid-naive women diagnosed with stage 0 to III breast cancer at the age of 66 to 90 years between 2008 and 2013, this study estimated overall and quarterly adjusted probabilities of new-onset persistent opioid use, which was defined as receiving ≥90 days' supply of opioids in the year after active breast cancer treatment. Sensitivity analyses were conducted with an alternative definition of persistent opioid use: any opioid fill 90 to 180 days after active cancer treatment. RESULTS: Nearly two-thirds of the subjects received prescription opioid therapy during cancer treatment. Quarterly probabilities of new-onset persistent opioid use after active treatment ranged from 2% to 4%; in sensitivity analyses, the alternative outcome definition resulted in predicted probabilities ranging from 11.4% to 14.7%. Subjects with more advanced disease, a higher comorbidity burden, a low-income status, and greater opioid exposure during active cancer treatment were more likely to develop persistent opioid use. CONCLUSIONS: Persistent opioid use was an infrequent occurrence among older adult patients with breast cancer completing cancer treatment between 2008 and 2013. This finding was encouraging because of the concerning opioid trends seen in noncancer populations. However, opportunities to further mitigate unsafe opioid use as a complication of cancer care, including standardization of persistent opioid use definitions, should be explored. Cancer 2020;126:814-822.

This cohort study examines rates and estimated risk of adverse drug events associated with opioid use in the year after cancer treatment among older adults who survived breast cancer.

Rates of opioid-related EDVs and hospitalizations, as well as concurrent opioid and benzodiazepine use, vary geographically. More research is needed to examine factors that impact regional variation and what influences the concurrent use of opioids and benzodiazepines.