Houten, Holly Van

Introduction: Previous studies have shown inconsistent changes in the rates of adverse cardiovascular events after daylight savings time (DST) transitions. In this large-scale, U.S.-based nationwide study, we sought to investigate the association of DST transitions with the rates of adverse cardiovascular events. Methods: The study cohort included 36,116,951 unique individuals from de-identified administrative claims data of the OptumLabs Data Warehouse®. There were 74,722 total adverse cardiovascular events during the week of DST transition and the control weeks (two weeks prior and after) in spring and autumn of 2015-2019. We used Bayesian hierarchical Poisson regression models to estimate the event rate ratios (ERR) representing the ratio of composite adverse cardiovascular event rates (acute myocardial infarction, stroke, cardiogenic shock, cardiac arrest, and sudden death) between DST transition weeks and control weeks. Results: Our results showed an average increase of 3% [95% uncertainty interval; -3% to 10%] and 4% [-2% to 12%] in the rate of adverse cardiovascular events during Monday and Friday of the spring DST transition week, respectively. The probability of spring DST transition being associated with a moderate-to-large increase in the event rates (ERR>1.10) was estimated to be <6% for Monday and Friday, and <1% for the remaining days. During autumn DST transition, the probability of any decrease in adverse cardiovascular event rates was estimated to be <46% and a moderate-to-large decrease in the event rates to be <4% across all days of the week. Conclusions: Spring DST transition week had a suggestive association with a minor increase in adverse cardiovascular event rates on Monday and Friday. The probability of this association to be of clinically meaningful magnitude was estimated to be very low. We did not observe any evidence suggestive of a change in adverse cardiovascular event rates immediately following autumn DST transition. Taken together, our findings, based on a large, diverse cohort from across the United States, suggest that DST transitions are unlikely to significantly impact the rate of cardiovascular events.

Introduction: OAC are recommended for AF patients with CHA 2 DS 2 -VASc ≥2 in men or ≥3 in women (high-risk group), may be considered in patients with CHA 2 DS 2 -VASc 1 in men or 2 in women (medium-risk group), and are reasonable to omit in patients with CHA 2 DS 2 -VASc 0 in men or 1 in women (low-risk group). Furthermore, NOACs are recommended over warfarin in most AF patients. This study aimed to investigate AF stroke prevention treatment patterns in patients managed in routine practice, in particular, the under-use of OAC in the high-risk group and over-use in the low-risk group. Methods: Adult patients with AF were identified using de-identified claims for commercial and Medicare Advantage enrollees in the OptumLabs Data Warehouse. Prescription fills were assessed within 90 days of a patient’s AF encounter between 1/1/2016-12/31/2020. Patients with other indications for OAC, such as VTE, recent joint replacement, prior mechanical or bioprosthetic valve replacement, rheumatic mitral stenosis, and patients who underwent LAAO were excluded. Results: Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, medium-, and high-risk groups, respectively. The mean age was 51.2 ±10.5 yr, 59.9 ±9.4 yr, and 75.1 ±8.8 yr. In the low-risk group, 29.6% were treated with OAC, whereas in the high-risk group, 40.3% were not treated with any antithrombotic therapy and 7.5% used thienopyridine only. Although 71% of patients on OAC were on a NOAC, the proportion of patients on NOAC decreased from 91% in the low-risk group to 69% in the high-risk group. Conclusions: There are potentially both under-use of guideline-recommended stroke prevention therapies in the high-risk patients and over-use in the low-risk group. Because patients at a high risk of stroke are also at a high risk of major and intracranial bleeding who might benefit from NOACs, the decreased use of NOAC in high-risk patients might highlight the need for future quality improvement efforts.

Introduction: Recent studies showed post-operative atrial fibrillation (POAF) is associated with increased stroke risk - even approaching that of unprovoked AF. This raises the question of whether patients with POAF should receive anticoagulation. We aim to compare different anticoagulation strategies in patients with POAF after cardiac and non-cardiac surgeries. Methods: Using a large national administrative database (OptumLabs Data Warehouse), we identified 33,981 patients with POAF between 1/1/2013-9/30/2019. Patients were divided to four groups based on the initial treatment within 30 days of POAF: (1) no anticoagulation (N=28,807) (2) apixaban (N=2178) (3) rivaroxaban (N=1320) (4) warfarin (N=1676). Follow up started at the 30 th day after POAF to exclude patients who died shortly after surgery and minimize immortal time bias. The follow up continued until patients changed treatment strategies, insurance, or died. 1:1 propensity score matching was performed between each anticoagulant to no treatment to balance on 86 baseline characteristics. Results: The mean age was 71.1±11.2 yr; mean CHA 2 DS 2 -VASc was 4.1±1.8; 29.1% received cardiac surgeries; 15.2% received anticoagulation within 30 days of POAF. The event rate per 100 person years was 1.58 for stroke in no-anticoagulation group, and 1.29 for anticoagulation group; 2.86 for major bleeding in no-anticoagulation group and 4.50 for anticoagulation group. After matching, apixaban and rivaroxaban were associated with a lower risk of stroke, but a higher risk of major bleeding; warfarin was not associated with a lower risk of stroke, but a higher risk of major bleeding (Figure). The effect was consistent across subgroups, e.g., age and surgery type. Conclusions: In patients with POAF, the stroke rate was lower than what was typically observed in clinical AF. Treatment with apixaban and rivaroxaban immediately after POAF was associated with a reduced risk of stroke but an increased risk of major bleeding.

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. Methods and Results: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74–0.85]; P <0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39–1.69] and odds ratio, 1.42 [95% CI, 1.3–1.53]; P <0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. Conclusions: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

Abstract Background: Proteasome inhibitors and immunomodulatory drugs are currently an integral part of the management of multiple myeloma. Pre-clinical and clinical studies suggest that bortezomib, the first approved proteasome inhibitor for the management of multiple myeloma, may be associated with an increased risk of cardiac events such as heart failure (HF), acute myocardial infarction (MI), and arrhythmia. The goal of this study was to evaluate the rate of adverse cardiac events in patients treated with bortezomib compared to lenalidomide. Methods: This retrospective, propensity-matched study using a large, national administrative claims database included multiple myeloma patients who initiated bortezomib and a comparison group (matched on age, sex, year of drug initiation, baseline HF, hyperlipidemia, hypertension, history of MI, arrhythmia and Charlson comorbidity index) who initiated lenalidomide between January 2008 and December 2014. Those who received both bortezomib and lenalidomide were excluded from the analysis. The primary endpoints were time to hospitalization for HF, acute MI and arrhythmia. Rates of hospitalizations were computed per 100 patient years (PY). Cox proportional hazard models were used to obtain hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 1,128 patients (564 bortezomib users and 564 lenalidomide users, mean age of 69, 47% female, and average follow-up time of 438 days) were included in the analysis. The rate of hospitalization for HF, acute MI, and arrhythmia was 5.76/100 PY, 2.57/100 PY, and 3.10/100 PY respectively among bortezomib users and 2.45/100 PY, 1.47/100 PY, and 2.85/100 PY respectively among lenalidomide users. In the propensity score matched models, the risk of hospitalization for acute MI and arrhythmia with bortezomib was similar to lenalidomide (HR 1.60 [95% CI 0.73-3.49] and HR 1.01 [95% CI 0.54-1.90] respectively). The risk of hospitalization for HF with bortezomib use was significantly higher compared to lenalidomide (HR 2.10 [95% CI 1.18-3.74], Figure 1). Further stratification of the patient population by baseline HF status showed that those with baseline HF (n=212) were significantly more likely to be hospitalized for HF following treatment with bortezomib compared to lenalidomide. The rate of hospitalization for HF in the population with baseline HF was 24.12/100 PY among bortezomib users and 8.77/100 PY among lenalidomide users (HR 2.24 [95% CI 1.04-4.83]). Those without baseline HF (n=916) had similar rates of hospitalization for HF when treated with bortezomib and lenalidomide (2.83/100 PY and 1.29/100 PY respectively, HR 2.05 [95% CI 0.86-4.91]). Conclusion: The current study shows that bortezomib use in patients treated for multiple myeloma is associated with an increased risk of hospitalization for heart failure, but not acute MI or arrhythmia. Those with HF prior to initiating therapy with bortezomib had a significantly increased risk of hospitalization for HF when compared to those treated with lenalidomide. There was no significant difference in the rate of hospitalization for HF in those without a baseline diagnosis of HF. Collectively, these data have important implications for the management of patients with multiple myeloma, especially those with a history of HF at the time of therapy initiation. Figure 1. Kaplan Meier plot for HF hospitalizations. Figure 1. Kaplan Meier plot for HF hospitalizations. Disclosures No relevant conflicts of interest to declare.

Background There is significant practice variation in oral anticoagulation ( OAC ) use following catheter ablation for atrial fibrillation. It is not clear whether the risk of cardioembolism increases after discontinuation of OAC following catheter ablation. Methods and Results We identified 6886 patients within a large national administrative claims database who underwent catheter ablation for atrial fibrillation between January 1, 2005, and September 30, 2014. We assessed the effect of time off of OAC by CHA 2 DS 2 ‐ VAS c score (after adjusting for other comorbidities) on risk of cardioembolism, using Cox proportional hazards models. There was an increase in the use of non–vitamin K OAC after ablation from 0% in 2005 to 69.8% in 2014. OAC discontinuation was high, with only 60.5% and 31.3% of patients remaining on OAC at 3 and 12 months, respectively. The rate of discontinuation was higher in low‐risk patients (82% versus 62.5% at 12 months for CHA 2 DS 2 ‐ VAS c 0–1 versus ≥2, respectively; P <0.001). Stroke occurred in 1.4% of patients with CHA 2 DS 2 ‐ VAS c ≥2 and 0.3% of those with CHA 2 DS 2 ‐ VAS c 0 or 1 over the study follow‐up. The risk of cardioembolism in the first 3 months after ablation was increased among those with any time off OAC (hazard ratio 8.06 [95% CI 1.53–42.3], P <0.05). The risk of cardioembolism beyond 3 months was increased with OAC discontinuation among high‐risk patients (hazard ratio 2.48 [95% CI 1.11–5.52], P <0.05) but not low‐risk patients. Conclusion The overall risk of stroke in postablation patients is low; however, OAC discontinuation after ablation is common and is associated with increased risk of cardioembolism for all patients within the first 3 months and for high‐risk patients in the long term. Continuing OAC for at least 3 months in all patients and indefinitely in high‐risk patients appears to be the safest strategy.

We measured the financial consequences of new CRC treatment regimens. New regimens have increased cost directly through price and indirectly through nonstandard and second-line regimen use.