Objective:To determine the risk of hospitalization and death associated with pimavanserin use.Methods:We conducted a retrospective cohort study of adults 65 years and older with Parkinson’s disease between November 1, 2015 and December 31, 2018 using an administrative dataset on residents of Medicare-certified long-term care facilities and linked Medicare claims data. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance pimavanserin users and nonusers on 24 baseline characteristics. Fine-Gray competing risk and Cox proportional hazards regression models were used to estimate the risk of hospitalization and death up to one year, respectively.Results:The study cohort included 2,186 pimavanserin users and 18,212 nonusers. There was a higher risk of 30-day hospitalization with pimavanserin use vs. nonuse (IPTW adjusted hazard ratio [aHR] 1.24, 95% confidence intervals [CI] 1.06–1.43). There was no association of pimavanserin use with 90-day hospitalization (aHR 1.10, CI 0.99–1.24) nor with 30-day mortality (aHR 0.76, CI 0.56–1.03). Pimavanserin use vs. nonuse was associated with an increased 90-day mortality (aHR 1.20, CI 1.02–1.41) that persisted after 180 days (aHR 1.28, CI 1.13–1.45) and 1 year (aHR 1.56, CI 1.42–1.72).Conclusions:Pimavanserin use vs. nonuse in older adults was associated with an increased risk of hospitalization at one month of initiation and a higher risk of death for up to one year following initiation. These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.Classification of Evidence:This study provides Class II evidence that in patients with Parkinson’s disease who are 65 or older and residing in Medicare-certified long-term care facilities, pimavanserin prescribing is associated with an increased risk of 30-day hospitalization and higher 90-, 180-, and, 365-day mortality.

Many drugs have been used in the treatment of COVID-19 since the beginning of the pandemic. In a large multicenter cohort study of 137 870 individuals hospitalized with confirmed or suspected COVID-19, investigators assessed temporal and institutional variation in the use of 3 of the most widely used drugs: hydroxychloroquine, remdesivir, and dexamethasone.

Background Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non‐valvular atrial fibrillation (NVAF). Methods We used Surveillance, Epidemiology, and End Results (SEER)‐Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively. Results Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA₂DS₂‐VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27–1.90 for score ≥6 vs. 1) or with lower HAS‐BLED scores (HR 1.96, 95% CI 1.67–2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA₂DS₂‐VASc scores (odds ratio [OR] 0.53, 95% CI 0.33–0.84 for score ≥6 vs. 1). Conclusions Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

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BACKGROUND: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin. METHODS: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death. RESULTS: Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92–2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70–1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59–0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69–0.94]) compared to warfarin users. CONCLUSIONS: Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

Objective: Despite population-level increases in use of direct oral anticoagulants (DOACs) over the last decade, less is known about their use among individuals with cancer and non-valvular atrial fibrillation (NVAF). We quantified DOAC initiation and switching among such individuals. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus). We limited the cohort to continuously enrolled beneficiaries with newly diagnosed NVAF following cancer diagnosis (from 2010 to 2016) who did not have any oral anticoagulant use during the 12-months prior to their NVAF diagnosis. We evaluated the initiation of warfarin or DOACs within 3 months of the incident NVAF diagnosis. Among warfarin users, we determined switching rates to DOACs and among DOACs users, we determined switching rates to warfarin. Descriptive statistics were used for all the analyses. Results: Of 1,028,784 Medicare beneficiaries with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 19,513 cancer patients diagnosed with incident NVAF. Lung (20.2%), Breast (19.2%), prostate (19.2%) and colorectal (16.0%) cancer accounted for over three-fourths of the cohort. Overall, 7,604 patients (39%) initiated oral anticoagulants. Among these patients, 4,223/7,604 (55.5%) and 3,381/7,604 (44.5%) initiated DOACs and warfarin, respectively. Patients who initiated DOACs had lower Charlson comorbidity score (1.0 ± 1.4 vs. 1.3 ± 1.5) and CHA 2 DS 2 -VASc score (4.4 ± 1.7 vs. 4.8 ± 1.7) compared to warfarin users. Initiation of DOACs varied by cancer type; for example, 13.6% (55/405) of patients with stomach cancer initiated DOACs, whereas 29.8% (1120/3755) of patients with prostate cancer initiated DOACs. Among patients who initiated any oral anticoagulants, the use of DOACs increased from 22% (110/501) in 2011 to 75.3% (1335/1772) in 2016, whereas warfarin use declined from 78% (391/501) to 24.7% (437/1772). The switching rate among warfarin initiators to DOACs (623/3381, 18.4%) was higher than the switching rate among DOACs initiators to warfarin (281/4223, 6.7%). Conclusion: Among cancer patients with newly diagnosed NVAF, the use of DOACs has markedly increased from 2011 to 2016, with a corresponding decline in the use of warfarin. Moreover, cancer patients are more likely to switch from warfarin to DOACs. Our findings highlight the dynamic life cycle of these products and the value of real-world assessments of their comparative safety and effectiveness among Medicare beneficiaries.

Objective: Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death. Results: Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91). Conclusion: Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.